Interventions for impetigo

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Authors

Sander Koning1, Renske van der Sande1, Arianne P Verhagen1, Lisette WA van Suijlekom-Smit2,
Andrew D Morris3, Christopher C Butler4, Marjolein Berger1, 5, Johannes C van der Wouden1

Background - Methods - Results - Characteristics of Included Studies - References - Data Tables & Graphs


1Department of General Practice, Erasmus Medical Center, Rotterdam, Netherlands [top]
2Department of Paediatrics, Paediatric Rheumatology, Erasmus MC - Sophia Children's Hospital, Rotterdam, Netherlands [top]
3Department of Dermatology, University of Wales College of Medicine, Cardiff, UK [top]
4Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK [top]
5Department of General Practice, University Medical Centre Groningen, Groningen, Netherlands [top]

Citation example: Koning S, van der Sande R, Verhagen AP, van Suijlekom-Smit LWA, Morris AD, Butler CC, Berger M, van der Wouden JC. Interventions for impetigo. Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD003261. DOI: 10.1002/14651858.CD003261.pub3.

This is a Cochrane Skin Group External Web Site Policy systematic review.

Contact person

Johannes C van der Wouden

Department of General Practice and Elderly Care Medicine, EMGO Institute for Health and Care Research
VU University Medical Center
PO Box 7057
1007 MB Amsterdam
Netherlands

E-mail: j.vanderwouden@vumc.nl

Dates

Assessed as Up-to-date: 27 July 2010
Date of Search: 27 July 2010
Next Stage Expected: 01 October 2011
Protocol First Published: Issue 4, 2001
Review First Published: Issue 2, 2004
Last Citation Issue: Issue 1, 2012

What's new

Date / Event Description
09 June 2015
Amended

Author information (affiliation) updated

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History

Date / Event Description
07 March 2012
Amended

The lead author's contact details have been updated.

08 November 2011
New citation: conclusions not changed

A substantial amount of new information has been added in the form of 12 newly included studies.

08 November 2011
Updated

New search for studies

29 July 2011
Feedback incorporated

In response to peer reviewers' comments, the following major changes were implemented: (1) removed sumscore for risk of bias items; (2) dropped intention to treat analysis as separate risk of bias item; (3) provided more precise information on subjective assessment of symptoms; (4) made a separate table for adverse events.

04 August 2010
Amended

When finalizing the update, new searches were run (2009-July 2010), resulting in the addition of eight papers to the list of Studies awaiting assessment.

23 February 2009
New citation: conclusions changed

New search (2002-2008), 12 new trials found, one trial previously included discarded. Tables with outcomes of methodological assessments replaced by 'Risk of bias' tables. New author added.

03 October 2008
Amended

Converted to new review format.

02 September 2004
Updated

Minor update

04 January 2003
Amended

New studies found but not yet included or excluded

27 November 2002
New citation: conclusions changed

Substantive amendment

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Abstract

Background

Impetigo is a common, superficial bacterial skin infection, which is most frequently encountered in children. There is no generally agreed standard therapy, and guidelines for treatment differ widely. Treatment options include many different oral and topical antibiotics as well as disinfectants. This is an updated version of the original review published in 2003.

Objectives

To assess the effects of treatments for impetigo, including non-pharmacological interventions and 'waiting for natural resolution'.

Search methods

We updated our searches of the following databases to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials, and we handsearched the reference lists of new studies found in the updated search.

Selection criteria

Randomised controlled trials of treatments for non-bullous, bullous, primary, and secondary impetigo.

Data collection and analysis

Two independent authors undertook all steps in data collection. We performed quality assessments and data collection in two separate stages.

Main results

We included 57 trials in the first version of this review. For this update 1 of those trials was excluded and 12 new trials were added. The total number of included trials was, thus, 68, with 5578 participants, reporting on 50 different treatments, including placebo. Most trials were in primary impetigo or did not specify this.

For many of the items that were assessed for risk of bias, most studies did not provide enough information. Fifteen studies reported blinding of participants and outcome assessors.

Topical antibiotic treatment showed better cure rates than placebo (pooled risk ratio (RR) 2. 24, 95% confidence interval (CI) 1.61 to 3.13) in 6 studies with 575 participants. In 4 studies with 440 participants, there was no clear evidence that either of the most commonly studied topical antibiotics (mupirocin and fusidic acid) was more effective than the other (RR 1.03, 95% CI 0.95 to 1.11).

In 10 studies with 581 participants, topical mupirocin was shown to be slightly superior to oral erythromycin (pooled RR 1.07, 95% CI 1.01 to 1.13). There were no significant differences in cure rates from treatment with topical versus other oral antibiotics. There were, however, differences in the outcome from treatment with different oral antibiotics: penicillin was inferior to erythromycin, in 2 studies with 79 participants (pooled RR 1.29, 95% CI 1.07 to 1.56), and cloxacillin, in 2 studies with 166 participants (pooled RR 1.59, 95% CI 1.21 to 2.08).

There was a lack of evidence for the benefit of using disinfectant solutions. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments (RR 1.15, 95% CI 1.01 to 1.32).

The reported number of side-effects was low, and most of these were mild. Side-effects were more common for oral antibiotic treatment compared to topical treatment. Gastrointestinal effects accounted for most of the difference.

Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.

Authors' conclusions

There is good evidence that topical mupirocin and topical fusidic acid are equally, or more, effective than oral treatment. Due to the lack of studies in people with extensive impetigo, it is unclear if oral antibiotics are superior to topical antibiotics in this group. Fusidic acid and mupirocin are of similar efficacy. Penicillin was not as effective as most other antibiotics. There is a lack of evidence to support disinfection measures to manage impetigo.

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Plain language summary

Interventions for the skin infection impetigo

 

Impetigo causes blister-like sores. The sores can fill with pus and form scabs, and scratching can spread the infection. Impetigo is caused by bacteria. It is contagious and usually occurs in children. It is the most common bacterial skin infection presented by children to primary care physicians. Treatment options include topical antibiotics (antibiotic creams), oral antibiotics (antibiotics taken by mouth), and disinfectant solutions. There is no generally agreed standard treatment, and the evidence on what intervention works best is not clear.

We identified 68 randomised controlled trials comparing various treatments for impetigo. Altogether, these studies evaluated 26 oral treatments and 24 topical treatments, including placebo, and results were described for 5708 participants.

Overall, topical antibiotics showed better cure rates than topical placebo.

Two antibiotic creams, mupirocin and fusidic acid, are at least as effective as oral antibiotics where the disease is not extensive. There was no clear evidence that either of these most commonly studied topical antibiotics was more effective than the other.

Topical mupirocin was superior to the oral antibiotic, oral erythromycin.

We found that the oral antibiotic, oral penicillin, is not effective for impetigo, while other oral antibiotics (e.g. erythromycin and cloxacillin) can help.

It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo.

There is a lack of evidence to suggest that using disinfectant solutions improves impetigo. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments.

Reported side-effects for topical treatments were mild and low in frequency; the treatments sometimes resulted in itching, burning, or staining. Oral antibiotics produced gastrointestinal complaints, such as nausea and diarrhoea, in 2% to 30% of participants, depending upon the specific antibiotic.

Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.

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Background

Description of the condition

Biology and symptoms

Impetigo or impetigo contagiosa is a contagious superficial bacterial skin infection most frequently encountered in children. It is typically classified as either primary (e.g. direct bacterial invasion of previously normal skin), secondary, or common impetigo (where the infection is secondary to some other underlying skin disease that disrupts the skin barrier, such as scabies or eczema). Impetigo is also classified as bullous or non-bullous impetigo. Bullous impetigo simply means that the skin eruption is characterised by bullae (blisters). The term 'impetigo contagiosa' is sometimes used to mean non-bullous impetigo, and at other times it is used as a synonym for all impetigo.

Non-bullous impetigo is the most common form of impetigo. The initial lesion is a thin-walled vesicle on previously normal skin that rapidly ruptures. It then leaves superficial erosion covered with yellowish-brown or honey-coloured crusts. The crusts eventually dry, separate, and disappear, leaving a red mark that heals without scarring. The most frequently affected areas are the face and limbs. The lesions are sometimes painful. Usually, there are no systemic symptoms such as fever, malaise, or anorexia. Swelling of the lymph nodes draining the infected area of skin is common. It is believed that, in most cases, spontaneous resolution may be expected within two to three weeks without treatment but more prompt resolution occurs with adequate treatment. Diagnostic confusion can occur with a variety of skin disorders including shingles, cold sores, cutaneous fungal infections, and eczema (Hay 1998; Resnick 2000). Pyoderma is sometimes used as a synonym for impetigo in tropical countries. This is usually to denote streptococcal, as opposed to staphylococcal, impetigo.

Bullous impetigo is characterised by larger bullae or blisters that rupture less readily and can persist for several days. Usually there are fewer lesions and the trunk is affected more frequently than in non-bullous impetigo. Diagnostic confusion can occur with thermal burns, blistering disorders (e.g. bullous pemphigoid), and Stevens Johnson syndrome.

Causes

Staphylococcus aureus (S. aureus) is considered to be the main bacterium that causes non-bullous impetigo. However, Streptococcus pyogenes (S. pyogenes), or both S. pyogenes and S. aureus, are sometimes isolated from the skin. In moderate climates, staphylococcal impetigo is more common, whereas in warmer and more humid climates, the streptococcal form predominates. In moderate climates, the relative frequency of S. aureus infections has also changed with time (Dagan 1993). It was predominant in the 1940s and 1950s, after which Group A streptococci became more prevalent. In the past two decades, S. aureus has become more common again. Bullous impetigo is always caused by S. aureus.

Secondary impetigo may occur as a complication of many dermatological conditions (notably eczema). The eruption appears clinically similar to non-bullous impetigo. Usually S. aureus is involved. The underlying skin disease may improve with successful treatment of the impetigo, and the converse may also be true.

Complications of non-bullous impetigo are rare, but local and systemic spread of infection can occur that may result in cellulitis, lymphangitis, or septicaemia. Non-infectious complications of S. pyogenes infection include guttate psoriasis, scarlet fever, and glomerulonephritis (an inflammation of the kidney that can lead to kidney failure). It is thought that most cases of glomerulonephritis result from streptococcal impetigo rather than streptococcal throat infection, and this has always been an important rationale for antibiotic treatment. The incidence of acute glomerulonephritis has declined rapidly over the last few decades. Baltimore 1985 stated that the risk of developing glomerulonephritis is not altered by treatment of impetigo; however, certain subtypes of Group A streptococci are associated with a much greater risk (Dillon 1979b).

Epidemiology

In the Netherlands, most people with impetigo consult their general practitioner and only approximately 1% of the cases are referred to a dermatologist (Bruijnzeels 1993). Although the incidence of impetigo in general practice has been declining, recent data show an increase in consultations for impetigo (Koning 2006; Van den Bosch 2007). Impetigo is still a common disease particularly in young children. It is the third most common skin disorder in children after dermatitis/eczema and viral warts (Bruijnzeels 1993; Dagan 1993; Mohammedamin 2006). Impetigo is the most common skin infection that is presented in general practice by children aged one to four years of age (Mohammedamin 2006). In British general practice, 2.8% of children aged 0 to 4 and 1.6% aged 5 to 15 consult their GP about impetigo each year (McCormick 1995). In the Netherlands in the late 1980s, the consultation rate was 1.7% of all children under 18 years of age; this increased to 2.1% in 2001 (Koning 2006). Peak incidence occurs between the ages of one and eight years (Koning 2006). In some tropical or developing countries the incidence of impetigo seems to be higher than elsewhere (Canizares 1993; Kristensen 1991).

Description of the intervention

Management options for impetigo include the following:

  1. no pharmacological treatment, waiting for natural resolution, hygiene measures;
  2. topical disinfectants (such as saline, hexachlorophene, povidone iodine, and chlorhexidine);
  3. topical antibiotics (such as neomycin, bacitracin, polymyxin B, gentamycin, fusidic acid, mupirocin, retapamulin, or topical steroid/antibiotic combination); and
  4. systemic antibiotics (such as penicillin, (flu)cloxacillin, amoxicillin/clavulanic acid, erythromycin, and cephalexin).

The aim of treatment includes resolving the soreness caused by lesions and the disease's unsightly appearance (especially on the face), as well as preventing recurrence and spread to other people. An ideal treatment should be effective, cheap, easy to use, and accepted by people. It should be free from side-effects, and it should not contribute to bacterial resistance. For this reason, antibiotics should not have an unnecessarily broad spectrum (Espersen 1998; Smeenk 1999), and if a topical antibiotic is used, it should, preferably, not be one which may be needed for systemic use (Carruthers 1988; Smeenk 1999).

Waiting for natural resolution could be acceptable if the natural history were known and benign. Impetigo is considered to be self-limiting by many authors (Hay 1998; Resnick 2000). However, there are no robust data on the natural history of impetigo. Reported cure rates of placebo creams vary from 8% to 42% at 7 to 10 days (Eells 1986; Ruby 1973). Topical cleansing used to be advised in the 1970s as an alternative for antibiotic treatment, but this was later said to be no more effective than placebo (Dagan 1992). Guidelines and treatment advice often do not mention topical cleansing as a treatment because the main concern is preventing the spread of the infection to other children.

A choice has to be made between topical and systemic antibiotic treatment, although in some situations clinicians prescribe both topical and systemic antibiotics. An advantage of the use of topical antibiotics is that the drug can be applied where it is needed, avoiding systemic side-effects such as gastrointestinal upset. Also, compliance may be better (Britton 1990).

The disadvantages of using topical antibiotics include the risks of developing bacterial resistance and sensitisation, e.g. developing an allergic contact dermatitis to one of the constituents of the topical preparation (Carruthers 1988; Smeenk 1999). This is especially common with the older antibiotics, such as gentamycin, bacitracin, and neomycin (Smeenk 1999). Some preparations (e.g. tetracycline) can cause staining of the skin and clothes.

Staphylococcal resistance against penicillin and erythromycin is common (Dagan 1992). Bacterial resistance against the newer topical antibiotics, such as mupirocin ointment and fusidic acid ointment, is increasing (Alsterholm 2010; de Neeling 1998). Another advantage of the newer topical antibiotics is that mupirocin is never, and fusidic acid not often, used systemically.

How the intervention might work

All treatment options listed above aim to either eradicate or prevent growth of the bacteria.

Why it is important to do this review

Guidelines concerning treatment vary widely - some recommend oral antibiotic treatment, others local antibiotic treatment or even just disinfection in mild cases (Hay 1998; Resnick 2000) - so clinicians have many treatment options. The evidence on what works best is not clear. There is potential conflict between what is in the best interest of the individual and what would best benefit the community in terms of cost and the increase in antibiotic resistance.

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Objectives

To assess the effects of treatments for impetigo, including waiting for natural resolution.

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Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials.

Types of participants

We included people who have impetigo or impetigo contagiosa diagnosed by a medically trained person (and preferably confirmed by bacterial culture). We recorded whether or not bacterial culture was performed. The diagnosis could be either non-bullous or bullous impetigo. Studies using a broader diagnostic category such as 'bacterial skin infections' or 'pyoderma' were eligible if a specific subgroup with impetigo could be identified, for which the results were separately described. Studies on secondary impetigo or impetiginised dermatoses were included.

Types of interventions

We included any program of topical or systemic (oral, intramuscular, or intravenous) treatment, including antibiotics, disinfectants, or any other intervention for impetigo, such as 'awaiting natural response'. We excluded studies that only compared different dosages of the same drug.

Types of outcome measures

Primary outcomes
  1. Cure as defined by clearance of crusts, blisters, and redness as assessed by the investigator.
  2. Relief of symptoms such as pain, itching, and soreness as assessed by participants.
Secondary outcomes
  1. Recurrence rate.
  2. Adverse effects such as pain, allergic sensitisation, and complications.
  3. Development of bacterial resistance.

Search methods for identification of studies

We aimed to identify all relevant randomised controlled trials (RCTs) regardless of language or publication status (published, unpublished, in press, or in progress).

Electronic searches

We updated our searches of the following databases on 27 July 2010:

  • the Cochrane Skin Group Specialised Register using the following search terms: (impetig* or pyoderma or ((staphylococc* or streptococc*) and skin and infection*)) and (therap* or treatment* or intervention*);
  • the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library using the search strategy in Appendix 1;
  • MEDLINE (from 2005 to the present) using the search strategy in Appendix 2;
  • EMBASE (from 2007 to the present) using the search strategy in Appendix 3; and
  • LILACS (Latin American and Caribbean Health Science Information database, from 1982 to the present) using the search strategy in Appendix 4.

Please note: The UK and US Cochrane Centres have an ongoing project to systematically search MEDLINE and EMBASE for reports of trials which are then included in the CENTRAL database. Searching has currently been completed in MEDLINE, from inception to 2004 and in EMBASE, from inception to 2006. Further searches of these two databases to cover the years not searched by the UK and US Cochrane Centres for CENTRAL were undertaken for this review as described above.

A final prepublication search for this review was undertaken on 16 August 2011. Although it has not been possible to incorporate RCTs identified through this search within this review, relevant references are listed under Studies awaiting classification. They will be incorporated into the next update of the review.

Ongoing Trials

We updated our searches of the following ongoing trials databases on 3 August 2010, using the terms 'impetigo' and 'pyoderma':

Searching other resources

Handsearching

We handsearched the Yearbook of Dermatology (1938 to 1966) and the Yearbook of Drug Therapy (1949 to 1966) for the pre-PubMed era.

References from published studies

We checked references from published studies, including secondary review articles, for further studies.

Unpublished literature

We corresponded with authors and pharmaceutical companies to search for unpublished studies and grey literature.

Language

We did not apply any language restrictions.

Data collection and analysis

Selection of studies

Two authors (JCvdW and SK or RvdS) independently read all abstracts or citations of trials. If one of the authors thought the article might be relevant, a full copy of the article was acquired for further data collection. The reasons for exclusion were recorded for every excluded abstract or citation. Only full reports were included. Two authors independently screened all full-copy articles (LvSS, SK, RvdS, JCvdW). The articles were selected according to the inclusion criteria. Reasons for exclusion were recorded on a specially-designed registration form (see the 'Characteristics of excluded studies' table). In the case of doubt, the opinion of a third author was obtained. Many trials studied a range of (skin) infections including impetigo. Frequently, the results of the subgroup of impetigo participants were not reported separately. In these studies, provided they were published in the last 10 years, we contacted trial authors and asked them to provide the results of the subgroup of impetigo participants. We obtained data in this way in only two instances (Blaszcyk 1998; Claudy 2001).

Data extraction and management

Two authors (ADM and CCB), using a pre-piloted data abstraction form, carried out the full data extraction. The form contained key elements such as time and setting of the study, participant characteristics, bacterial characteristics, type of interventions, outcomes, and side-effects. We resolved disagreements with the help of a third author (SK).

For this update, RvdS and JCvdW carried out data extraction from newly included papers. When studies assessed outcome measures more than once, we included the assessment that was nearest to one week after the start of therapy. When studies had more than two arms and two of these arms were different dosages of the same drug, we combined these arms.

Assessment of risk of bias in included studies

Assessment of methodological quality

Two independent authors (JCvdW, RvdS and/or AV) assessed the methodological quality of all trials according to the updated guidelines (Higgins 2008). Because we could not read the Japanese study by Ishii 1977, this 'Risk of bias' table was completed by Tetsuri Matsumura. The two studies on which authors of this review were co-authors (Koning 2003; Koning 2008) were assessed by other authors. The items that were addressed are shown in the 'Risk of bias' table. For feasibility reasons, the methodological quality assessment was not performed under masked conditions. There is no consensus over whether assessment should be done blinded for authors, institutions, journal, or publication year (Jadad 1998).

Unit of analysis issues

In the case of studies with more than two treatment arms, we deemed that pooling these studies under separate comparisons, without adjustment, would result in unit-of-analysis errors (overcounting). Should this have occurred, the problem was to be solved by dividing the group size by the number of comparisons.

Assessment of heterogeneity

We used the I² statistic to assess statistical heterogeneity, with I² statistic > 50% regarded as substantial heterogeneity.

Data synthesis

Where there was no statistical evidence of heterogeneity we used the fixed-effect model to estimate effects. Otherwise, we used the random-effects model. For dichotomous outcomes we reported risk ratios with 95% confidence intervals.

Sensitivity analysis

We prespecified the following factors for sensitivity analyses:

  1. the quality of the studies;
  2. whether there was observer blinding;
  3. whether there was just a clinical diagnosis or bacterial swab confirmation;
  4. primary versus secondary impetigo;
  5. bullous versus non-bullous; and
  6. staphylococcal or streptococcal predominance.

During the update, we decided that an overall quality score per study was not useful. Furthermore, most trials were observer-blind, took bacterial swabs, studied primary impetigo, and had staphylococcal predominance. Sensitivity analyses for these items were, therefore, not possible.

When we analysed the data we decided to consider the results for bullous and non-bullous impetigo separately.

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Results

Results of the search

Our initial search identified approximately 700 papers, 221 of which were selected for full copy reading. For this update, we identified more than 1000 additional papers. Two reviewers screened titles and abstracts, after which, approximately, 60 papers were studied in full copy.

Included studies

For the first version of the review we included 56 papers describing 57 trials. This update identified 12 additional studies, of which 2 were published before 2000 (Farah 1967; Ishii 1977). One study, which was previously included, was excluded because it turned out not to be a randomised trial (Park 1993), bringing the total number of included studies to 68. The lists of ongoing studies (Ongoing studies) and studies awaiting assessment (Studies awaiting classification) show studies that might be eligible for a future update of this review. Regarding the excluded studies, we only report on the most relevant ones (Excluded studies; Characteristics of excluded studies).

Most trials were reported in the English language. Four included studies were reported in Japanese, and one paper each was reported in Thai, Portuguese, Spanish, French, and Danish (some of these had abstracts and tables in English). Trials in Russian, Chinese, German, and French were among those that were excluded (not for language reasons). In instances where none of the authors were competent in the language of the paper, translators provided assistance.

We found an appreciable number of studies from the early 1940s (e.g. MacKenna 1945). These studies were often carried out in military populations, in which impetigo was a frequent disease at the time. These study reports did not meet the inclusion criteria of our review because of inadequate randomisation. The distribution of the included studies by decade is as follows: 1960s - 1 study, 1970s - 5 studies (7%), 1980s - 31 studies (46%), 1990s - 20 studies (29%), and 2000 to 2008 - 11 studies (16%). Five included studies evaluating mupirocin were presented at an international symposium in 1984; we found no publication other than the conference proceedings for three of these (Kennedy 1985; Rojas 1985; Wainscott 1985). Two were published elsewhere as well (Eells 1986; Gould 1984).

Design

All studies were parallel group trials, but there were important design differences between the studies. As mentioned before, many trials included participants with infections other than impetigo, while some trials studied only impetigo. Ages of included participants differed widely, as some studies were carried out exclusively in either adults or children. The average age of study participants in trials that studied a range of skin infections was usually higher than in studies focusing on impetigo alone. With the exception of four studies (Faye 2007; Ishii 1977; Rice 1992; Vainer 1986), all studies performed bacteriological investigations. Although a number of studies explicitly stated that participants with a negative culture were excluded, other studies may also have excluded culture negative participants without reporting those exclusions. No study reported a predominantly streptococcal impetigo. The only studies not to report a preponderance of staphylococcal impetigo were Mertz 1989 and Ruby 1973 (carried out in Puerto Rico and Texas respectively).

Sample sizes

The 68 studies had a total of 5578 evaluable participants; this is an average of 82 participants and a median of 60.5 participants per study (see the 'Characteristics of included studies' tables). In 23 studies the number of participants with impetigo was less than 50; in 10 studies it was less than 20.

Setting

Twenty-nine of the studies were carried out in North America (in 13 Canadian/Northern states, in 8 Southern states, in 8 multicentres), 15 in Europe, 9 in Central/South America, 10 in Asia, 1 in Africa, and 4 were worldwide multicentre trials. Most studies were carried out in hospital out-patient clinics (paediatrics or dermatology, 60 studies), but some were carried out in general practice.

Participants

Only three studies exclusively addressed participants with bullous impetigo (Dillon 1983; Ishii 1977; Moraes Barbosa 1986). Seven trials included both bullous and non-bullous impetigo participants (Barton 1989; Ciftci 2002; Dagan 1992; Koning 2008; Kuniyuki 2005; Oranje 2007; Pruksachat 1993). Three studies on secondary impetigo were included (Fujita 1984; Rist 2002; Wachs 1992). Three other trials included both primary and secondary impetigo participants (Faye 2007; Gonzalez 1989; Tamayo 1991). Thirty-nine trials studied impetigo alone whereas 29 trials studied participants with a range of (usually skin) infections, impetigo being 1 of them. This was the typical study design when a new antibiotic was studied. This type of study design imposed problems in retrieving outcome data as the outcomes were often presented for all the participants together. We included these studies only if the main outcome measure was presented separately for the subgroup of impetigo participants.

Interventions

The 68 trials evaluated 50 different treatments (26 oral treatments and 24 topical treatments - both including placebo). The systemic treatments that were studied were all administered orally (tablets). A total of 74 different comparisons were made. Some comparisons were made in several studies; some studies made more than one comparison. Sixty-eight comparisons were made only once. Six different comparisons were made in more than 1 trial, especially when topical mupirocin was studied (topical mupirocin versus oral erythromycin was considered in 10 studies, mupirocin versus fusidic acid was considered in 4 studies, mupirocin versus placebo was considered in 3 studies). For each of these comparisons we pooled the outcomes of the different studies (see Data and analyses).

The most common type of comparison was between 2 different oral antibiotic treatments (29 studies including duplicates). Cephalosporins (15 studies) and macrolide antibiotics, especially erythromycin and azithromycin (9 studies), were most often involved. A topical antibiotic treatment was compared with an oral antibiotic treatment in 22 studies. Nineteen of these comparisons contained erythromycin, mupirocin, or both.

Only two trials studied antiseptic or disinfecting treatments (Christensen 1994; Ruby 1973).

Only seven placebo controlled trials were found (Eells 1986; Gould 1984; Ishii 1977; Koning 2003; Koning 2008; Rojas 1985; Ruby 1973). The latter is the only trial that compared an oral treatment with placebo.

Three studies had three arms but the treatment in two of these were different dosages of the same drug (Blaszcyk 1998; Bucko 2002a; Bucko 2002b). We combined these arms. Nine other studies had more than two arms but with different treatments: three arms (Bass 1997; Demidovich 1990; Dux 1986; Rodriguez-Solares 1993; Vainer 1986; Wachs 1976), four arms (Kuniyuki 2005; Moraes Barbosa 1986), and five arms (Ruby 1973). Only two of the comparisons in these multiple-arm studies could be pooled with other studies: erythromycin versus penicillin V from Demidovich 1990, and mupirocin versus erythromycin from Dux 1986. For this reason we refrained from adjusting for multiple treatment comparisons.

Outcomes

Cure as assessed by investigator was our main outcome measure. This was often not defined. Researchers sometimes combined the categories 'cured' and 'improved' and presented those participants as one group. The length of follow-up varied widely, and it was sometimes not even specified; however, we tried to retrieve the data for follow up as close as possible to seven days after the start of treatment. The development of bacterial resistance to the study drug was reported in only 10 studies.

Excluded studies

One hundred and sixty-five of the studies did not meet the inclusion criteria for the first version of the review, and 33 more were excluded when updating the review (see the 'Characteristics of excluded studies' tables). The most common reasons included the following: the study was not about impetigo, the outcomes of impetigo participants were not reported separately, or studies were not randomised.

Studies awaiting classification

In the previous version of this review, four studies were awaiting classification. For this update two of these studies were included (Ciftci 2002; Claudy 2001) and two were excluded (Liu 1986; Parish 2000).

Ten studies that were found during the update process are listed in the 'Characteristics of studies awaiting classification' tables, as are a further 6 studies that were identified at the prepublication search. We are currently unable to include or exclude these due to insufficient information about them. We hope to fully incorporate them into future updates of this review.

Ongoing studies

Seven studies that were found during the update process are listed in the 'Characteristics of ongoing studies' tables. These will be fully incorporated into future updates of this review when they are completed.

Risk of bias in included studies

For many of the items that were assessed, the studies did not provide enough information (Figure 1; Figure 2).

Sequence generation

Fourteen of the studies reported an adequate generation of the randomisation scheme. All other papers did not report on this item.

Allocation (selection bias)

All but two of the included studies were described as randomised as this was a selection criterion. For two papers in Japanese, this was unclear, and these papers were given the benefit of the doubt (see Figure 1). Most papers did not describe the method of randomisation in detail, so the method could not be judged as appropriate. Only 19 of the 68 studies provided information on allocation concealment. In most cases (18 of 19), treatment allocation was considered to be concealed.

Blinding (performance bias and detection bias)

In many cases it was not clear whether the participant, the caregiver, or the outcome assessor were blinded. A total of 15 studies were considered to be adequately blinded (see Figure 1). In 24 studies, at least 1 party was considered not to be blinded. In 29 papers, the information was insufficient to judge blinding.

Inclusion and exclusion criteria of the trials

In 10 of our included studies, the inclusion and exclusion criteria of the trial were not specified in more detail than saying 'patients with impetigo' (see Figure 1).

Incomplete outcome data (attrition bias)

In some studies, high numbers lost to follow up were recorded. Thirty-four studies either included an intention-to-treat analysis or had fewer than 10% dropouts balanced between groups. For some other studies, an intention-to-treat analysis could be calculated from the data presented in the study.

Effects of interventions

Primary outcomes: 1) clinical cure

The first primary outcome was clinical cure (or improvement) as assessed by the investigator. When this was assessed more than once, we only included the assessment that was nearest one week from commencement of treatment.

Under the following two main headings ('non-bullous impetigo' and 'bullous impetigo') we have grouped all studies that either included only primary impetigo, combined primary and secondary impetigo, or did not specify whether participants had primary or secondary impetigo. The third heading 'secondary impetigo' addresses all studies that focused exclusively on secondary impetigo (see Background for an explanation).

(a) Non-bullous impetigo

(i) Topical antibiotics
Topical antibiotics versus placebo (six studies, four comparisons)

Overall topical antibiotics showed better cure rates or more improvement than placebo (pooled risk ratio (RR) 2.24, 95% CI 1.16 to 3.13 using a random-effects model, I² = 53%) (see Analysis 1.1). This result was consistent for mupirocin (RR 2.21, 95% CI 1.59 to 3.05; 3 studies - Eells 1986; Gould 1984; Rojas 1985) (see Analysis 1.1), fusidic acid (RR 4.42, 95% CI 2.39 to 8.17; 1 study - Koning 2003) (see Analysis 1.1), and retapamulin (RR 1.64, 95% CI 1.30 to 2.07; 1 study - Koning 2008) (see Analysis 1.1). In one small study (Ruby 1973), bacitracin did not show a significant difference in cure rate compared with placebo (RR 3.71, 95% CI 0.16 to 85.29) (see Analysis 1.1).

Topical antibiotic versus another topical antibiotic (14 studies, 15 comparisons)

Only one topical antibiotic showed superiority over another topical antibiotic - in a single study: gentamycin over neomycin (RR 1.43, 95% CI 1.03 to 1.98; Farah 1967) (see Analysis 2.1). Also from a single study, the difference between retapamulin over fusidic acid was not statistically significant (RR 1.05, 95% CI 1.00 to 1.11; Oranje 2007) (see Analysis 2.1). There were 12 different comparisons: 4 studies (Gilbert 1989; Morley 1988; Sutton 1992; White 1989) compared mupirocin with fusidic acid (RR 1.03, 95% CI 0.95 to 1.11) (see Analysis 2.1), and the remaining 11 were all only represented by a single study.

Topical antibiotics versus oral (systemic) antibiotics (16 studies, 17 comparisons)

Pooling 10 studies which compared mupirocin with oral erythromycin showed significantly better cure rates, or more improvement, with mupirocin (RR 1.07, 95% CI 1.01 to 1.13) (see Analysis 3.1). However, no significant differences were seen between mupirocin and dicloxacillin (Arredondo 1987), cephalexin (Bass 1997), or ampicillin (Welsh 1987). Bacitracin was significantly worse than oral cephalexin in one small study (Bass 1997), but no difference was seen between bacitracin and erythromycin (Koranyi 1976), or penicillin (Ruby 1973).

A sensitivity analysis on the influence of blinding the outcome assessor on the comparison of mupirocin versus erythromycin (10 studies) revealed that there was no clear relationship between blinding of the outcome assessor and the outcome.

Pooling the 2 studies with observer blinding (Britton 1990; Dagan 1992) showed high heterogeneity (I² statistic = 79%) and resulted in a non-significant difference between the 2 drugs (random-effects model, RR 1.12, 95% CI 0.86 to 1.46) (see Analysis 3.2).

Topical antibiotics versus disinfecting treatment (two studies)

In one study (Ruby 1973), no statistically significant difference in cure/improvement was seen when bacitracin was compared to hexachlorophene (RR 3.71, 95% CI 0.16 to 85.29) (see Analysis 4.1). In another study (Christensen 1994), there was a tendency for fusidic acid cream to be more effective than hydrogen peroxide, but this just failed to reach statistical significance (RR 1.14, 95% CI 1.00 to 1.31) (see Analysis 4.1). When the 2 studies were pooled, topical antibiotics were significantly better than disinfecting treatments (fixed-effect model, RR 1.15, 95% 1.01 to 1.32, I² statistic 0%) (see Analysis 4.1).

Topical antibiotic versus antifungal (one study)

Only one study compared a topical antibiotic to an antifungal, comparing topical mupirocin to topical terbinafine (Ciftci 2002). No statistical difference was seen (RR 1.39, 95% CI 0.98 to 1.96) (see Analysis 5.1).

Topical antibiotic + oral antibiotic vs topical antibiotic + oral antibiotic (one study, three comparisons)

In a four-armed study, three arms addressed the following combinations of a topical antibiotic and an oral antibiotic: topical tetracycline combined with oral cefdinir compared to topical tetracycline combined with oral minomycin, topical tetracycline combined with oral cefdinir compared to topical tetracycline combined with oral fosfomycin, and topical tetracycline combined with oral minomycin compared to topical tetracycline combined with oral fosfomycin (Kuniyuki 2005). None of the three comparisons showed a statistically significant difference (see Analysis 6.1).

Topical antibiotic versus topical antibiotic + oral antibiotic (one study, three comparisons)

The fourth arm of the study described under the previous heading (Kuniyuki 2005) was tetracycline. None of the comparisons with the other three treatments (see above) showed a statistically significant difference (see Analysis 7.1).

(ii) Oral antibiotics
Oral antibiotics versus placebo (one study)

A single study (Ruby 1973) found no significant difference between oral penicillin and placebo (RR 7.74, 95% CI 0.43 to 140.26) (see Analysis 8.1).

Oral antibiotic versus another oral antibiotic: cephalosporin versus another antibiotic (six studies)

All comparisons consisted of single studies (or arms of a single study); only one comparison - cephalexin versus penicillin - showed a significant difference (Demidovich 1990) (see Analysis 9.1).

Oral antibiotic versus another oral antibiotic: one cephalosporin versus another cephalosporin (seven studies)

No significant differences were seen between cephalexin and cefadroxil (Hains 1989), cefdinir (Giordano 2006; Tack 1997; Tack 1998); cefaclor and cefdinir (Arata 1989a), or cefditoren and cefadroxil (Bucko 2002b). Cefditoren turned out to be less effective than cefuroxime (Bucko 2002a) (see Analysis 10.1).

Oral antibiotic versus another oral antibiotic: macrolides (erythromycin, azithromycin, clindamycin) versus penicillins (penicillin V, dicloxacillin, amoxacillin, cloxacillin, flucloxacillin) (seven studies)

In two studies (Barton 1987; Demidovich 1990), erythromycin showed a better cure rate or more improvement than penicillin (pooled fixed-effect model, RR 1.29, 95% CI 1.07 to 1.56, I² statistic 0%) (see Analysis 11.1). The other five comparisons consisted of single studies, and they did not show significant differences between macrolides and penicillins.

Oral antibiotic versus another oral antibiotic: macrolide versus another macrolide (one study)

In a single study (Daniel 1991a), no difference in cure rate or improvement was seen between azithromycin and erythromycin (RR 1.18, 95% CI 0.88 to 1.58) (see Analysis 12.1).

Oral antibiotic versus another oral antibiotic: penicillin versus other oral antibiotics (including other penicillins) (four studies)

In 1 study (Dagan 1989), amoxicillin plus clavulanic acid showed a better cure rate than amoxicillin alone (RR 1.40, 95% CI 1.04 to 1.89) (see Analysis 13.1), but when amoxicillin plus clavulanic acid was compared with fleroxacin in another study (Tassler 1993), no significant difference was seen (RR 1.14, 95% CI 0.80 to 1.62) (see Analysis 13.1). Cloxacillin was significantly superior to penicillin in 2 studies (Gonzalez 1989; Pruksachat 1993) although these studies were statistically heterogeneous (I² statistic 57%) (pooled RR 1.59, 95% CI 1.21 to 2.08) (see Analysis 13.1).

Other comparisons of oral antibiotics (two studies)

In two studies (Arata 1989b; Claudy 2001), no difference in cure rates/improvement could be detected between lomefloxacin and norfloxacin nor between (oral) fusidic acid and pristinamycin (see Analysis 14.1).

Oral antibiotics versus disinfecting treatments (one study)

In a single small study (Ruby 1973), no difference in cure rates/improvement could be detected between penicillin and hexachlorophene (RR 7.74, 95% CI 0.43 to 140.26) (see Analysis 15.1).

(iii) Disinfecting treatments
Disinfecting treatments versus placebo (one study)

In a single small study (Ruby 1973), no participants in either the hexachlorophene (n = 11) or placebo group (n = 13) showed cure or improvement. Comparisons of disinfecting treatments with antibiotics are given above.

(b) Bullous impetigo
(i) Topical antibiotics
Topical antimicrobial versus placebo (one study)

In one study (Ishii 1977), topical Eksalbe simplex (a drug containing killed Eschelichia, Staphylococcus, Streptococcus, and Pseudomonas) was compared to placebo. The active drug turned out to be superior (cure/improvement RR 2.30, 95% CI 1.10 to 4.79) (see Analysis 16.1).

Topical antibiotics versus other topical antibiotics (one study, three comparisons)

In a small study (Moraes Barbosa 1986), fusidic acid was significantly more effective than both neomycin/bacitracin (RR 10.00, 95% CI 1.51 to 66.43) (see Analysis 17.1) and chloramphenicol (RR 5.00, 95% CI 1.38 to 18.17) (see Analysis 17.1). In the same study, no difference was detected between chloramphenicol and neomycin/bacitracin (RR 2.00, 95% CI 0.21 to 19.23) (see Analysis 17.1).

Topical antibiotics versus oral antibiotics (one study, three comparisons)

The same study (Moraes Barbosa 1986) showed that neomycin/bacitracin was significantly less effective than oral erythromycin (RR 0.14 95% CI 0.02 to 0.99) (see Analysis 18.1). There was no significant difference between either erythromycin and fusidic acid (RR 1.43, 95% CI 0.83 to 2.45) (see Analysis 18.1) or chloramphenicol (RR 0.29, 95% CI 0.07 to 1.10) (see Analysis 18.1).

(ii) Oral antibiotics
Oral antibiotic versus another oral antibiotic (one study)

No significant difference was seen between cephalexin and dicloxacillin (Dillon 1983; RR 1.17, 95% CI 0.95 to 1.45) (see Analysis 19.1).

(c) Secondary impetigo
(i) Topical antibiotics
Topical antibiotic versus oral antibiotic (one study)

No significant difference was seen between mupirocin and cephalexin (Rist 2002) (see Analysis 20.1).

Antibiotic versus steroid versus antibiotic plus steroid (one study)

In a three-armed study (Wachs 1976), the comparisons of betamethasone with gentamycin alone or with betamethasone plus gentamycin did not show significant differences (see Analysis 21.1 and Analysis 22.1). The combination of betamethasone and gentamycin cream was significantly more effective than gentamycin alone (RR 2.43, 95% CI 1.29 to 4.57) (see Analysis 23.1).

(ii) Oral antibiotics

In a very small study, no significant difference was detected between cephalexin and enoxacin (Fujita 1984) (see Analysis 24.1).

Primary outcomes: 2) relief of symptoms

The second primary outcome was relief of symptoms, such as pain, itching, and soreness, as assessed by study participants. Although some studies asked about overall satisfaction, acceptability, or treatment preference (McLinn 1988; Rice 1992; Rist 2002; Sutton 1992; White 1989), only one study asked participants to rate their symptoms at follow-up (Giordano 2006). However, this was a study addressing not only impetigo but other skin infections as well, and results for this outcome were not reported for impetigo separately.

Secondary outcomes: 1) recurrence rate

No relevant data were provided by any study for this outcome.

Secondary outcomes: 2) adverse effects

(i) Topical antibiotics

The trials included in this review usually reported few, if any, side-effects from topical antibiotics (see Table 1). The studies comparing mupirocin, bacitracin, and placebo reported none (Eells 1986; Ruby 1973). The study that compared fusidic acid to placebo recorded more side-effects in the placebo group (Koning 2003). Three of 4 studies comparing mupirocin with fusidic acid recorded side-effects: minor skin side-effects were reported for mupirocin by 10 out of 368 participants (3%) and for fusidic acid by 4 out of 242 participants (2%). The study that compared retapamulin to placebo found more itching in the group treated with retapamulin (7% vs 1%; P = 0.17) (Koning 2008). In the other study of retapamulin, this side-effect was reported in less than 1% of cases (Oranje 2007). Most other trials comparing topical antibiotics reported no side-effects or reported minor skin side-effects in low numbers (less than 5% of participants).

Topical versus oral treatments

Of the 10 trials comparing erythromycin with mupirocin, 9 reported side-effects. All trials recorded more side-effects from erythromycin, with the exception of two trials (Britton 1990 - equally divided minor gastrointestinal side-effects - and Rice 1992 - nil reported). Gastrointestinal side-effects (nausea, stomach ache, vomiting, diarrhoea) were recorded in 80 out of 297 participants (27%) in the erythromycin groups, versus 17 out of 323 participants (5%) in the mupirocin groups. Skin side-effects (itching, burning) were recorded in 5 out of 297 participants (2%) in the erythromycin groups versus 23 out of 323 participants (7%) in the mupirocin groups. Most other trials comparing topical and oral antibiotics did not record data on side-effects (see Table 1).

(ii) Oral antibiotics

Eleven of the 31 trials comparing oral antibiotics did not report on side-effects (see Table 1). Three of the 6 trials that studied erythromycin recorded side-effects; the highest frequency was reported by Faye 2007: 11/65 participants reported gastrointestinal side-effects (mainly diarrhoea). The other trials, usually making unique comparisons, mainly reported gastrointestinal side-effects in small percentages. In five trials, a considerable difference in side-effects was reported. Gastrointestinal complaints were recorded in 1 out of 113 participants (10%) in the enoxacin group compared to 4 out of 110 participants (4%) in the cefalexin group (Fujita 1984). Fourteen out of 327 (4%) of the cefadroxil-treated participants versus 2 out of 234 (1%) flucloxacillin-treated participants had 'severe' side-effects, such as stomach ache, rash, fever, and vomiting (Beitner 1996). Cefaclor caused more diarrhoea than amoxicillin plus clavulanic acid (5 out of 16 participants (31%) vs 2 out of 18 participants (11%)) (Jaffe 1985). Pristinamycin caused more upper and lower gastrointestinal side-effects than oral fusidic acid (12% vs 7% and 17% vs 2%, respectively) (Claudy 2001). Finally, the clindamycin group of participants reported more side-effects (any side-effect) than the dicloxacillin-treated group (Blaszcyk 1998).

(¡¡¡) Disinfecting treatments

Eleven per cent of the participants using hydrogen peroxide cream reported mild side-effects (not specified) versus seven per cent in the fusidic acid group (Christensen 1994). No participant was withdrawn from the study because of side-effects. No adverse effects of scrubbing with hexachlorophene were recorded (Ruby 1973) (see Table 1).

Secondary outcomes: 3) Development of bacterial resistance

Most studies either did not report on susceptibility of isolated pathogens to the study drugs or presented only baseline data. Ten studies provided information on the development of resistance to the study drug during the study period (Barton 1988; Bucko 2002a; Bucko 2002b; Dagan 1992; Giordano 2006; Goldfarb 1988; Gould 1984; Tack 1998; Tassler 1993; White 1989). In most of these studies, none or only a few of the participants' pathogens had developed resistance. The only exception was Dagan 1992, where 14/18 (78%) of positive cultures after 3 days of follow-up showed resistance to erythromycin, compared to 27/91 (28%) at baseline. The other study that included erythromycin (Goldfarb 1988) showed only 3% (1/32) resistance at follow-up.

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Discussion

Summary of main results

Overall, topical antibiotics showed better cure rates than topical placebo. No differences were found between the two most studied topical antibiotics: mupirocin and fusidic acid. Topical mupirocin was superior to oral erythromycin. In most other comparisons, topical and oral antibiotics did not show significantly different cure rates, nor did most trials comparing oral antibiotics. Penicillin V was inferior to erythromycin and cloxacillin, and there is a lack of evidence to suggest that using disinfectant solutions improves impetigo.

The reported number of side-effects was low. Oral antibiotic treatment caused more side-effects, especially gastrointestinal ones, than topical treatment. A striking finding is that the trials comparing erythromycin with mupirocin recorded more (gastrointestinal) side-effects in the erythromycin group than the trials that compared erythromycin with other oral antibiotics.

Overall completeness and applicability of evidence

The large number of treatments evaluated (50) supports the view that there is no widely accepted standard therapy for impetigo. Most studies did not contribute clear answers about the vast choice of treatment options. Many of the studies were underpowered; this is partly due to the fact that many trials included several skin infections, impetigo being only one of them (these studies are directed at the drug rather than at the disease). In many cases, significant differences became insignificant when impetigo participants were considered after excluding participants with other sorts of infection. Another drawback of this type of study is that the age of participants is much higher than the typical age at which people contract impetigo (e.g. Blaszcyk 1998; Bucko 2002a; Bucko 2002b; Kiani 1991). The dosage of studied antibiotics may differ between studies, complicating the comparability of studies; however, the same doses were usually used (e.g. erythromycin 40 mg/kg/day). Cure rates of specific treatments can be different between studies, e.g. of fusidic acid and mupirocin (Sutton 1992; White 1989). This may be explained by the fact that investigations were done in different regions and times, and inclusion criteria differed.

Little is known about the 'natural history' of impetigo. Therefore, the paucity of placebo-controlled trials is striking, given that impetigo can be considered a minor disease. Only seven placebo-controlled studies have been conducted (Eells 1986; Gould 1984; Ishii 1977; Koning 2003; Koning 2008; Rojas 1985; Ruby 1973). The 7-day cure rates of placebo groups in these studies varied but can be considerable (0% to 42%).

The disinfectant agents, such as povidone iodine and chlorhexidine, recommended in some guidelines (Hay 1998; Resnick 2000), usually as supplementary treatment, have been inadequately studied and not compared to placebo treatment. Hydrogen peroxide cream was not significantly less effective than fusidic acid (cure rate 72% versus 82%) in a relatively large trial (Christensen 1994). We judged that blinding in this trial was inadequate.

There is a commonly accepted idea that more serious forms of impetigo (e.g. participants with extensive lesions, general illness, fever) need oral rather than topical antibiotic treatment. This principle cannot be evaluated using the data included in our review as trials that study local treatments usually exclude participants with more serious forms of impetigo.

One of our primary outcomes was relief of symptoms, such as pain, itching, and soreness, as assessed by participants (or parents). Surprisingly, only one of the studies addressed this outcome (Giordano 2006).

Resistance patterns of staphylococci - which causes impetigo - change over time. Outcomes of studies dating back more than 10 years, which form the majority of trials in this review, may not be applicable to the current prevalence of infecting agents. Also, resistance between regions and countries may vary considerably. Thus, up-to-date, local characteristics and resistance patterns of the causative bacteria should always be taken into account when choosing antibiotic treatment. In addition, health authorities and other relevant bodies may advise against prescribing certain antibiotics for impetigo, in order to restrict the development of bacterial resistance and reserve these drugs for more serious infections.

Quality of the evidence

Although the total number of randomised trials we identified was considerable, the average number of participants per study was small. In this update, the newly added studies made this average increase from 62 to 84 per study. This was partly due to studies that assessed a range of infections and randomised a large number of participants, but in which those with impetigo were only a minority. Through the years, we found an increase in the quality of the studies; the average number of items scored positively increased from less than three in the 1970s to almost five for studies published in the new millennium. This is a problem shared with many other reviews. Details of the design of the studies were often lacking in the published reports, leading to a lot of question marks in the 'Risk of bias' tables.

Potential biases in the review process

Several studies included participants with impetigo next to participants with other conditions, but they did not report results of those with impetigo separately. However, as the number of participants with impetigo was often small in these studies, we do not expect that our conclusions would be different.

Three authors on this review are authors of one included trial (Sander Koning, Lisette WA van Suijlekom-Smit, Johannes C van der Wouden; Koning 2003), Sander Koning and Johannes C van der Wouden were also involved in a second trial (Koning 2008) which was initiated by the manufacturer of the drug. These authors were not involved in the assessment of the risk of bias for both studies.

Agreements and disagreements with other studies or reviews

Topical mupirocin and fusidic acid can be considered as effective as, or more effective than, oral antibiotics, and these topical agents have fewer side-effects. This finding is in sharp contrast to the previously held view that oral treatment is superior to topical treatment (Baltimore 1985; Tack 1998). Other topical antibiotics, excluding retapamulin, were generally inferior to mupirocin, fusidic acid, and oral antibiotics. The study by Vainer is an exception: no difference was seen between tetracycline/bacitracin cream, neomycin/bacitracin cream, and fusidic acid (Vainer 1986). Fusidic acid, mupirocin, and retapamulin are the only topical antibiotics that have been compared to placebo (and shown to be more effective).

For the results of the study comparing topical fusidic acid to retapamulin (Oranje 2007), the P value computed by Review Manager (RevMan) differs from the study report (0.07 in RevMan vs 0.062 in the study report) due to different methods (94.8% vs 90.1% cure, favouring retapamulin).

None of the studies reported cases of acute (post-streptococcal) glomerulonephritis. This complication has always been an important rationale for oral antibiotic treatment. This reported absence of glomerulonephritis may reflect the reduced importance of streptococci in impetigo. It should be noted that study sizes are small and glomerulonephritis is rare.

Several of the interventions used for impetigo have also been applied in other situations where Staphylococcus aureus, the main bacterium causing impetigo, plays a role. Here we review some of these, as reported in recently published Cochrane reviews. The effect of mupirocin ointment for preventing S. aureus infections in nasal carriers was superior to that of placebo or no treatment (van Rijen 2008). Birnie 2008 assessed interventions to reduce S. aureus in the management of atopic eczema, but the review did not find clear evidence of benefit for any of these. A review of the treatment of bacteraemia due to S. aureus is under way (Cheng 2009), as is a review of antibiotics for S. aureus pneumonia in adults (Shankar 2007). Mastitis in breastfeeding women is also caused by S. aureus. A recent Cochrane review found insufficient evidence to confirm or refute the effectiveness of antibiotic therapy (Jahanfar 2009).

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Authors' conclusions

Implications for practice

Implications for topical disinfectants in clinical practice

There is a lack of evidence from RCTs for the value of disinfecting measures in the treatment of impetigo, as a sole or supplementary treatment.

Implications for topical antibiotics in clinical practice

There is good evidence that the topical antibiotics mupirocin and fusidic acid are equal to, or possibly more effective than, oral treatment for people with limited disease. Fusidic acid, mupirocin, and retapamulin are probably equally effective; other topical antibiotics seem less effective. In general, oral antibiotics have more side-effects than topical antibiotics, especially gastrointestinal side-effects.

Implications for use of systemic antibiotics in clinical practice

What is stated in the previous paragraph regarding the comparison with topical antibiotics is equally relevant here. The only oral antibiotic that has been compared to placebo is penicillin, and this was in an old study (Ruby 1973): no difference was found, and the confidence interval was large. Based on the available evidence on efficacy, no clear preference can be given for B-lactamase resistant narrow-spectrum penicillins such as cloxacillin, dicloxacillin and flucloxacillin, or for broad spectrum penicillins such as ampicillin, amoxicillin with clavulanic acid, cephalosporins or macrolides.

General considerations regarding the choice of antibiotics

Other criteria, such as price, (unnecessary) broadness of spectrum, and wish to reserve a particular antibiotic for specific conditions, can be decisive. Resistance rates against erythromycin seem to be rising. In general, oral antibiotics have more side-effects, especially gastrointestinal ones. There is insufficient evidence to say whether oral antibiotics are better than topicals for more serious and extensive forms of impetigo. From a practical standpoint, oral antibiotics might be an easier option for people with very extensive impetigo.

Implications for research

Trials should be powered to compare treatments for a specific disease entity, rather than the effectiveness of a specific antibiotic on a variety of (skin) infections, as treatment may impact differently on separate subtypes of skin and soft tissue infections. As seen in this review, trials that study one treatment for several diseases often show inconclusive results for specific diagnoses. Future research on impetigo should make a careful power calculation as most included studies included too few participants with impetigo to meaningfully assess differences in treatment effect.

Establishing the natural course of impetigo without any form of antibiotic treatment would be useful. However, although impetigo can be considered a minor ailment, studies with a non-intervention arm seem ethically impracticable. Comparator treatments may include the best identified options for non-antibiotic management.

The relative absence of data on the efficacy of topical disinfectants is a research gap that needs to be filled. These agents may not contribute to antibiotic resistance, and they are cheap. This research may be of particular importance for developing countries.

Preferably, a trial on impetigo should:

  • not include participants with a variety of skin diseases and soft tissue infections. If it does, results should be presented separately by diagnosis;
  • focus on either bullous or non-bullous impetigo and on either primary or secondary impetigo;
  • report resistance rates of causative bacteria against the studied antibiotic and against reference antibiotics such as erythromycin, mupirocin and/or fusidic acid, at baseline and at follow-up;
  • use clear and objective outcome measures for cure and improvement of impetigo, instead of subjective judgements such as 'improved', 'satisfactory', and 'good response'. Key elements defining clinical cure could be absence of crusts, dryness, intactness, and absence of redness of skin. A parameter of improvement could be 'size of affected surface'. Choosing 'standard' follow-up periods, e.g. 7, 14, or 21 days, will facilitate the comparison of studies; and
  • include a placebo group, or at least a 'gold standard' reference group. For topical treatments, mupirocin or fusidic acid could be considered 'gold standard'.

As part of the issue of antibiotic resistance, impetigo studies that establish the contribution of the studied treatment to the development of bacterial resistance are desirable.

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Acknowledgements

The authors would like to thank the following people from the editorial base for their substantial contribution to this review: Finola Delamere, Philippa Middleton, and Tina Leonard. They would also like to thank Seungsoo Sheen for his help in assessing a Korean paper, Mingming Zhang for assessing two Chinese papers, Alain Claudy for providing the outcomes for the participants with impetigo in his study, and Tetsuri Matsumura for assessing the risk of bias and extracting data from Ishii 1977.

The Cochrane Skin Group editorial base would like to thank the following people who commented on this update: our Key Editor Sue Jessop, our Statistical Editor Jo Leonardi-Bee, our Methodological Editor Philippa Middleton, Inge Axelson who was the clinical referee, and Philip Pocklington who was the consumer referee.

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Contributions of authors

Conceiving the review - SK, JCvdW, and LvSS
Designing the review - SK, JCvdW, LvSS, CCB, and AM
Co-ordinating the review - SK and JCvdW
Data collection for the review - SK, JCvdW, and RvdS
Developing the search strategy - JCvdW
Undertaking searches - JCvdW, SK, and RvdS
Screening search results - JCvdW, SK, and RvdS
Organising retrieval of papers - JCvdW, SK, and RvdS
Screening retrieved papers against inclusion criteria - LvSS, SK, and RvdS
Appraising quality of papers - JCvdW, AV, and RvdS
Abstracting data from papers - CCB, AM, RvdS, and JCvdW
Writing to trial authors of papers for additional information - SK, RvdS, and JCvdW
Obtaining and screening data on unpublished studies - JCvdW, SK, and RvdS
Data management for the review - SK, RvdS, and JCvdW
Entering data into RevMan - SK, JCvdW, and RvdS
Analysis of data - SK, RvdS, and JCvdW
Interpretation of data - all authors
Providing a methodological perspective - JCvdW
Providing a clinical perspective - SK and CCB
Providing a policy perspective - SK and CCB
Writing the review - SK, RvdS, and JCvdW
Providing general advice on the review - all authors
Securing funding for the review - JCvdW
Performing previous work that was the foundation of current study - LvSS, JCvdW, and SK

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Declarations of interest

Three authors of this review are authors of one included trial (Sander Koning, Lisette WA van Suijlekom-Smit, Johannes C van der Wouden; Koning 2003).

Sander Koning and Johannes C van der Wouden were also involved in a second trial (Koning 2008), which was initiated by the manufacturer of the drug. As employees of Erasmus MC, Rotterdam, Johannes C van der Wouden and Sander Koning received research funding from GlaxoSmithKline for participating in a study comparing retapamulin to placebo in participants with impetigo. The funding was used to pay staff involved in field work. They were also involved in publishing the results. The study was included in the update of this review.

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Differences between protocol and review

In case of studies assessing cure at more than one point in time, the protocol did not specify what time point to select for data extraction. From the start of the review, we chose the assessment that was closest to one week from the start of treatment.

For this update, the scoring of methodological quality was changed into the newly recommended 'Risk of bias' table (Higgins 2008).We also used risk ratio as recommended by the Cochrane Skin Group.

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Published notes

Sponsored research

Industry sponsorship or organisation of the trial was declared to be present in 20 trials (29%): 5 mupirocin studies (Goldfarb 1988; Mertz 1989; Rist 2002; Wainscott 1985; White 1989), 2 with cefdinir (Tack 1997; Tack 1998), 2 with cefadroxil (Beitner 1996; Hains 1989), 2 with azithromycin (Daniel 1991a; Daniel 1991b), 2 with cefditoren (Bucko 2002a; Bucko 2002b); 2 with retapamulin (Koning 2008; Oranje 2007); 1 of amoxicillin plus clavulanic acid (Jaffe 1985), cefalexin (Dillon 1983; Giordano 2006), clindamycin (Blaszcyk 1998), and fusidic acid (Sutton 1992). Five trials (9%) were supported by other organisations. In the remaining 48 (67%) trials, no statement of sponsorship or funding was made (see Table 2 'Declared sponsorship or funding').

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Characteristics of studies

Characteristics of included studies

Arata 1989a

Methods

Time NR; Japan; range of infections (impetigo 13/265)

Participants
  • Age 15 to 82 years
  • M/F 150/115 (all participants)
  • Mainly S.aureus
Interventions
  1. cefdinir 100 mg, 3 td
  2. cefaclor 250 mg, 3 td
Outcomes

Outcomes of the trial

  1. 10 days, excellent/good/poor
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available in the abstract.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available in the abstract.

Blinding (performance bias and detection bias) Unclear risk

Quote: "....double-blind."

Comment: There was unclear blinding of the outcome assessor and caregiver. The participant was probably blinded (see also Figure 2). The test drug packages also included placebo capsules.

Incomplete outcome data (attrition bias) Low risk

35/300 participants were omitted in the analysis: 16/147 in the cefdinir group (8 due to no or delayed visit to hospital, others for several reasons), 19/153 in the cefaclor group (8 due to no or delayed visit to hospital, others for several reasons) (see table 2).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance.

Randomised? Unclear risk

Insufficient information was available in the abstract.

Were both inclusion and exclusion criteria specified? Unclear risk

Insufficient information was available in the abstract.

Arata 1989b

Methods

Time NR; Japan; range of skin infections (including impetigo 18/259)

Participants
  • All ages
  • M/F 162/97
  • Mainly S.aureus (data for all participants)
Interventions
  1. lomefloxacin 200 mg, 3 td
  2. norfloxacin 200 mg, 3 td
Outcomes

Outcomes of the trial

  1. 7 days, cured/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available in the abstract.

Allocation concealment (selection bias) Unclear risk

This was unclear.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...a double-blind clinical trial." It was unclear who was blinded (and how). The outcome assessor and caregiver were probably not blinded. The participant was probably blinded (see Figure 1 Dosing schedule).

Incomplete outcome data (attrition bias) Unclear risk

33/291 participants were omitted in the analysis: 15/147 in the NY-198 group, 17/144 in the norfloxacin group. There was insufficient information in the abstract and figures.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance.

Randomised? Low risk

Quote: "...were randomly allocated to one of the two drugs."

Were both inclusion and exclusion criteria specified? Unclear risk

Inclusion (quote): "...skin and soft tissue infections, patients > 15 years". There was no exclusion criteria.

Arredondo 1987

Methods

Time NR; Mexico city, Mexico; range of skin infections (including impetigo 55/61)

Participants
  • Average age 7 years
  • M/F 30/31
  • S.aureus 67%
Interventions
  1. mupirocin ointment 2%, 3 td, 5 to 10 days
  2. dicloxacillin 250 mg, 4 td, 5 to 10 days
Outcomes

Outcomes of the trial

  1. 10 days, cure
Notes

Open trial

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

This was not mentioned in the article.

Blinding (performance bias and detection bias) High risk

Quote: "In an open trial..." Participants received capsules or ointment. Neither the participant, caregiver, nor outcome assessor were blinded.

Incomplete outcome data (attrition bias) Low risk

3/61 participants were omitted in the analysis: 2/29 in the mupirocin group, 1/32 in the dicloxacillin group. Reasons for being non-evaluable for clinical outcome were not specified (but this was a small %).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias High risk

Baseline imbalance: more severe impetigo in the mupirocin group (9/32 vs 3/29, Table 1). There was no data on compliance.

Randomised? Low risk

Quote: "After obtaining informed consent, patients were randomly divided into two treatment groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...pediatric patients with skin infections of sufficient severity to require treatment with a antibiotic." Quote: "Patients who...were excluded from the trial."

Barton 1987

Methods

June to August 1986; Missouri, USA; outpatients; only impetigo

Participants
  • Children (age NR)
  • M/F 29/32
  • S.aureus 35/65, Streptococcus 2/65, both: 30%

PE

Interventions
  1. penicillin V 50 mg/kg/day in 4 dd, 10 ds
  2. erythromycin 40 mg/kg/day in 4 dd, 10 ds

Outcomes

Outcomes of the trial

  1. 7 days, failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available about sequence generation.

Allocation concealment (selection bias) Low risk

Quote: "The patients were assigned to receive either erythromycin or penicillin in a random, double-blind fashion by a pharmacist."

Comment: Participants and investigators enrolling participants could not foresee assignment. 

Blinding (performance bias and detection bias) Unclear risk

See above - it was not specified how this was done. It is unclear whether the caregiver, participant, or outcome assessor was blinded.

Incomplete outcome data (attrition bias) High risk

42/71 participants were omitted in the analysis - reasons and numbers were not specified for each group (6 due to negative culture, 21 not evaluable for effectiveness (not further specified), 6 due to no ascertained compliance, 3 due to no growth of S. aureus alone, 6 with S. aureus alone but not available for follow-up). 14 were left for analysis in the erythromycin group and 15 in the penicillin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Compliance and baseline comparability was unclear.

Randomised? Low risk

Quote: "The patients were assigned to receive either erythromycin or penicillin in a random, double-blind fashion by a pharmacist."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "All patients examined in the outpatient department between June and August 1986 with primarily non bullous impetigo were asked to participate in the study if they were not receiving antibiotics at the time of being seen at CGH, had not taken antibiotics during the preceding week..."

Barton 1988

Methods

June to August 1987; Missouri, USA; outpatients; only impetigo

Participants
  • 2 months to 16 years
  • M/F 55/45
  • S. aureus 46/100, S. pyogenes 9/100, both 25/199

PE

Interventions
  1. erythromycin 40 mg/kg/day in 4 dd, 10 ds
  2. dicloxacillin 25 mg/kg /day in 4 dd, 10 ds
Outcomes

Outcomes of the trial

  1. 5 to 7 days, cure + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "Participants were randomly assigned in a double-blind manner by the hospital pharmacist to receive..." Hence, participants and investigators enrolling participants could not foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

See above - not specified how and who was blinded.

Incomplete outcome data (attrition bias) High risk

41/100 participants were omitted in analysis - not specified for each group (12/100 were lost to follow up, but not stated from which group). 29 were left in the erythromycin group and 30 left in the dicloxacillin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Group assignment of non-compliant participants was unclear.

Randomised? Low risk

Quote: "Participants were randomly assigned in a double-blind manner by the hospital pharmacist to receive..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "During the months of June, July and August, 1987, 100 children with impetigo, from whom informed consent was obtained, were consecutively enrolled in the study."

Quote: "Exclusion criteria included..."

Barton 1989

Methods

June to August 1988; Missouri, USA; outpatients; only impetigo

Participants
  • 3 months to 16 years
  • M/F 49/48
  • S. aureus 80%

PNE

Interventions
  1. erythromycin 40 mg/kg/day in 3 dd, 7 days
  2. mupirocin ointment 2%, 3 td, 7 days
Outcomes

Outcomes of the trial

  1. 4 to 7 days, cured + improved
Notes

14% bullous

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

This was not mentioned in the article.

Blinding (performance bias and detection bias) High risk

Participant and caregiver were not blinded because they received either capsules or ointment. It is not mentioned in the article whether the outcome assessor was blinded (probably not, because the caregiver and participant were not blinded)

Incomplete outcome data (attrition bias) Low risk

1(/97) participant was omitted in the analysis, specified: 1/48 in the erythromycin group (lost to follow up), 0/49 in the mupirocin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Compliance was not reported.

Randomised? Low risk

Quote: "Participants were randomly assigned to receive either..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children over 6 weeks of age with a clinical diagnosis of impetigo were invited to participate in the study. Exclusion criteria included..."

Bass 1997

Methods

Time NR; Honolulu, Hawaii; hospital outpatients; only impetigo

Participants
  • Average age 3.8 years
  • Sex NR
  • S. aureus 41/48

PNE

Interventions

3 arms:

  1. cephalexin 50 mg/kg/day in 3 dd + placebo ointment, 10 days
  2. mupirocin ointment 2%, 3 td + liquid oral placebo
  3. bacitracin ointment 500 units/g, 3 td + liquid oral placebo

Outcomes

Outcomes of the trial

  1. 8 to 10 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "...clinical pharmacist assigned them by a table of random numbers to one of the three treatment groups".

Allocation concealment (selection bias) Low risk

See above and the quote: "The clinician, patients and their parents were not aware of which of the three treatment regimens they were assigned."

Comment: Central allocation - participants and investigators enrolling participants could not foresee assignment. 

Blinding (performance bias and detection bias) Low risk

Quote: "The clinician, patients and their parents were not aware of which of the three treatment regimens they were assigned."

Comment: The outcome assessor, participant, and caregiver were all blinded.

Incomplete outcome data (attrition bias) High risk

6/32 participants were omitted in the analysis: 0/10 in the cephalexin group, 5/12 in the mupirocin group, 1/10 in the bacitracin group (missing Imbalance for missing data).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was a baseline imbalance for size and type of lesion. Compliance was assessed in only 17 participants.

Randomised? Low risk

Quote: "...clinical pharmacist assigned them by a table of random numbers to one of the three treatment groups."

Were both inclusion and exclusion criteria specified? Low risk

Quoted from the referred article Demidovich: "Children presenting with impetigo to our clinic were eligible for the study. Exclusion criteria were..."

Beitner 1996

Methods

December 1992 to November 1994; 25 centres, Sweden; outpatients; range of skin infections (impetigo 60/327)

Participants
  • Age range 3 to 80 years
  • S. aureus 86% of 327, Streptococcus 14% of 327
  • Included only participants with bacteria sensitive to both drugs

PE

Interventions
  1. cefadroxil 40 mg/kg/day, 10 days
  2. flucloxacillin tablets 750 mg, 2 td, or susp 30 to 50 mg/kg/day in 2 to 3 dd, 10 days
Outcomes

Outcomes of the trial

  1. 10 to 12 days, cure/improved/failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

The method of concealment was not described.

Blinding (performance bias and detection bias) High risk

Quote: "...single blinded."

Quote: "Statistical analysis was performed blinded."

Comment: The participant, outcome assessor, and caregiver were probably not blinded because participants in both groups did not receive the same administrations of study drugs daily.

Incomplete outcome data (attrition bias) High risk

334/661 participants were missing mainly due to a lack of a bacterial culture sensitive to both drugs, and 351/661 were omitted from the primary analysis. 33 impetigo participants were included in the primary analysis. Exact reasons for not being evaluable and group assignment were not reported. 19/661 were omitted in the "ITT-analysis".

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "The randomization produced two comparable groups of patients with no differences in known prognostic factors." 

Comment: There was no compliance data.

Randomised? Low risk

Quote: "In this prospective single-blind comparative and randomized multicentre trial..."

Were both inclusion and exclusion criteria specified? Low risk

Table 1: Inclusion and exclusion criteria for the subjects participating in the study.

Blaszcyk 1998

Methods

Period NR; multicentre; Europe, Latin America, Asia; range of skin infections (impetigo 42/539)

Participants
  • 16 to 70 years (all participants)

PNE

Interventions
  1. clindamycin caps 150 mg, 4 td
  2. clindamycin caps 300 mg, 2 td
  3. dicloxacillin caps 250 mg, 4 td
Outcomes

Outcomes of the trial

  1. 7 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "Drug supplies were masked."

Comment: Insufficient information was available.

Blinding (performance bias and detection bias) Low risk

Quote: "Drug supplies were masked."

Quote: "Patients in all groups received four administrations of study drugs daily."

Comment: The outcome assessor, participant, and caregiver were probably all blinded.

Incomplete outcome data (attrition bias) Low risk

48/588 were omitted in the analysis: 16/196 in the clindamycin caps 150 mg group, 19/198 in the clindamycin caps 300 mg group, 20/194 in the dicloxacillin caps group. Proportions of participants who did not complete the study medication and reasons were ~ similar (table II). There were not only impetigo participants.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Compliance data was provided (table II) and well-balanced. The distribution of baseline characteristics was not provided.

Randomised? Low risk

Quote: "This prospective, double mask, randomized study..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients were selected based on..."

Quote: "Patients were ineligible if..."

Britton 1990

Methods

October 1988 to October 1989; Portsmouth, Virginia, USA; outpatients; only impetigo

Participants
  • 2 months to 12 years
  • M/F 27/17
  • S. aureus 26/48

PNE

Interventions
  1. erythromycin 40 mg/kg/day in 4 dd + placebo cream
  2. mupirocin ointment 2%, 3 td + placebo susp
Outcomes

Outcomes of the trial

  1. 10 days, cured + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups."

Allocation concealment (selection bias) Low risk

Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups."

Comment: central allocation - pharmacy-controlled.

Blinding (performance bias and detection bias) Low risk

Quote: "The child group assignment was not known to parents or investigators."

Quote: "...assigned each patient to one of two groups: orally administered erythromycin plus topically applied placebo (erythromycin group) or orally administered placebo plus topically applied mupirocin (mupirocin group)."

Comment: The outcome assessor, participant, and caregiver were probably all blinded.

Incomplete outcome data (attrition bias) Low risk

6/54 participants were omitted in the analysis: 2/24 in the mupirocin group, 4/30 in the erythromycin group. Participants not completing the study were left out of the analysis. Reasons for not completing the study were not specified for each group. 3 were lost to follow up, 2 dropped out when misdiagnosis was suspected, and 1 was removed because of S. pyogenes pharyngitis. < 20% withdrawals and numbers were balanced.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias High risk

Baseline characteristics were imbalanced (sex, severity), and compliance was also skewed.

Randomised? Low risk

Quote: "Using a random numbers table, the hospital pharmacist randomly assigned each patient to one of the groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children aged 12 years and younger with the clinical diagnosis of impetigo..."

Quote: "We excluded..."

Bucko 2002a

Methods

Unlear, around 2000; US, multicentre; ambulatory setting; range of skin infections (including impetigo 58/857)

Participants
  • 12 to 93 years
  • M/F 427/430
  • S.aureus 525/1685, S.pyogenes 53/1685 (including Bucko 2002b)

PNE

Interventions
  1. cefditoren 200 mg, 2 td, 10 days
  2. cefditoren 400 mg, 2 td, 10 days
  3. cefuroxime 250 mg, 2 td, 10 days
Outcomes

Outcomes of the trial

  1. 7 to 14 days, cured or improved/li>
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not reported.

Allocation concealment (selection bias) Low risk

Quote: "Study-drug containers were dispensed in numeric sequence at each investigative site as patients were enrolled to ensure random assignment."

Blinding (performance bias and detection bias) Low risk

Quote: "...double-blind, double-dummy..."

Quote: "Patients' evaluability and outcomes were assessed under blinded conditions". The outcome assessor, caregiver, and participant were all blinded.

Incomplete outcome data (attrition bias) Low risk

For only impetigo: 2/58 missing impetigo participants in total - 0/19 in the cefditoren 200 mg group, 2/21 in the cefditoren 400 mg group, 0/18 in the cefuroxime 250 mg group. Reasons for missing participants were not specified (but a small % were non-evaluable)

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no compliance data and no baseline imbalance.

Randomised? Low risk

Quote: "Patients were randomized."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Eligible patients included..."

Quote: "Study exclusion criteria included..."

Bucko 2002b

Methods

Unclear, around 2000; US; multicentre; ambulatory setting; range of skin infections (including impetigo 74/828)

Participants
  • 12 to 95 years
  • M/F 428/400
  • S.aureus 525/1685, S.pyogenes 53/1685 (including Bucko 2002a)

PNE

Interventions
  1. Cefditoren 200 mg, 2 td, 10 days
  2. Cefditoren 400 mg, 2 td, 10 days
  3. Cefadroxil 500 mg, 2 td, 10 days
Outcomes

Outcomes of the trial

  1. 7 to 14 days, cured or improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not reported.

Allocation concealment (selection bias) Low risk

Quote: "Study-drug containers were dispensed in numeric sequence at each investigative site as patients were enrolled to ensure random assignment."

Blinding (performance bias and detection bias) Low risk

Quote: "...double-blind, double-dummy..."

Quote: "Patients' evaluability and outcomes were assessed under blinded conditions".

Comment: The outcome assessor, caregiver, and participant were all blinded.

Incomplete outcome data (attrition bias) Low risk

For only impetigo: 4/74 missing participants - 1/27 in the cefditoren 200 mg group, 0/25 in the cefditoren 400 mg group, 3/22 in the cefadroxil 500 mg group. Reasons for missing participants were not specified (but a small % were non-evaluable)

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no compliance data and no baseline imbalance.

Randomised? Low risk

Quote: "Patients were randomized..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Eligible patients included..."

Quote: "Study exclusion criteria included..."

Christensen 1994

Methods

Time NR; Sweden, Germany, UK; Outpatients (Germany) and GP (UK), both (Sweden); only impetigo

Participants
  • 3 + years
  • M/F 131/125
  • S.aureus 199/256, S.pyogenes 21/256, both 36/256

PE

Interventions
  1. hydrogen peroxide cream 1% (Microcid), 2 to 3 td, max 21 days
  2. fusidic acid cream gel 2%, 2 to 3 td, max 21 days
Outcomes

Outcomes of the trial

  1. evaluation time NR, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Quote: "...randomized (in blocks of four)." The process for selecting the blocks was not specified.

Allocation concealment (selection bias) Unclear risk

Quote: "The tubes were put into identical paper boxes, to keep the trials blind."

Comment: Insufficient information was available. The tubes may have been different.

Blinding (performance bias and detection bias) Unclear risk

Quote: "The tubes were put into identical paper boxes, to keep the trials blind." There was incomplete blinding - participants were probably not blinded (see above), and blinding with regard to the outcome assessor and caregiver is unclear.

Incomplete outcome data (attrition bias) Low risk

135/391 participants were omitted in the analysis because they were culture negative (not specified per group); 11/156 participants in the M-group and 3/156 in the F-group were withdrawn due to deterioration of their impetigo (statistically significant), 3/156 in the F-group and 0/156 in the M-group were withdrawn due to adverse events (irritation of the skin, burning, and blistering). All participants fulfilling the prespecified requirement of bacteriologically-verified impetigo were analysed.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no data on baseline comparability and compliance.

Randomised? Low risk

Quote: "...randomized (in blocks of four)."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were included"

Quote: "Patients were not allowed... prior to start of study..."

Ciftci 2002

Methods

1999; Turkey; hospital outpatient department; only impetigo

Participants
  • Age 10 to 132 months
  • M/F 32/16
  • S. aureus around 70%
Interventions
  1. topical mupirocin 2% 3td for 10 days
  2. topical terbinafine 1% 3td for 10 days
Outcomes

Outcomes of the trial

  1. 10 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) High risk

Quote: "...mupirocin group was instructed to use Bactroban 2% ointment and terbinafine group was instructed to use Lamisil 1% cream topically three times daily for ten days". The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) High risk

14/62 participants were not analysed: 6/31 were missing in the mupirocin group, 8/31 were missing in the terbinafine group. Quote: "At the end of the treatment, 25 participants in the mupirocin group and 23 participants in the terbinafine group were considered eligible" . > 20% missing.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias High risk

Quote: "The group had similar features except for the time from appearance of lesions to hospital admission." There was a mean of 5.44 in the mupirocin group versus 6.78 in the terbinafine group.

Randomised? Low risk

Quote: "...in a randomized fashion."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were excluded."

Quote: "....children, less than 12 years old, presenting with impetigo to..."

Claudy 2001

Methods

Time NR; France; ambulatory setting (dermatology outpatient departments); range of skin infections (including impetigo 53/334)

Participants
  • All participants: age > 18 years
  • M/F 206/128
  • S aureus: 162/334; S pyogenes 34/334
Interventions
  1. oral fusidic acid 2 x 250 mg 2 td for 7.5 days
  2. oral pristinamycin 2 x 500 mg 2 td for 10 days
Outcomes

Outcomes of the trial

  1. 11 days, cured and improved
Notes

Outcome data for impetigo participants was provided by the author (personal communication).

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Afin de garantir le double insu, chaque patient recevait le traitement dont 2.5 jours de placebo". [To ensure double blinding, each patient received a placebo for 2.5 days]. The participants were blinded, but blinding is unclear with regard to the caregiver and outcome assessor. 

Incomplete outcome data (attrition bias) Low risk

313/334 participants were analysed (< 10% not in analysis). There is no data for impetigo participants.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data and no baseline comparison.

Randomised? Low risk

Quote: "Une etude multicentrique, prospective, randomisée..." [A randomised, prospective, multicentre study...]

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Tout patient ambulatoire, âgé de plus de 18 ans, avec une pyodermite superficielle nécessitant une antibiothérapie orale et ayant donné son consentement éclairé pouvait être inclus dans l'essai à condition de ne presenter aucun des critères d'exclusion suivants." [Most ambulatory participants, older than the 18 years old, with a superficial pyoderma requiring oral antibiotics and with given informed consent could be included in the study provided there were none of the following exclusion criteria present.]

Dagan 1989

Methods

May to October 1987; Negev region, Israel; outpatients; only impetigo

Participants
  • 6 months to 9 years
  • Sex NR
  • S. aureus 37/51, S. pyogenes 14/51

PE

Interventions
  1. amoxicillin trihydrate syrup 40 mg/kg/day, in 3 dd, 10 days
  2. amoxicillin/clavulanic acid syrup 40 + 10 mg/kg/day, in 3 dd, 10 days
Outcomes

Outcomes of the trial

  1. 5 days, cure + improved
Notes

There was missing data from the first follow-up measurement for 4/26 participants in the amoxicillin trihydrate syrup group and 3/25 participants in the amoxicillin/clavulanic acid syrup group.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...in a double-blind fashion". It is unclear whether the outcome assessor, participant, or caregiver were blinded.

Incomplete outcome data (attrition bias) Low risk

7/52 (< 20%) participants were omitted in the analysis after 5 days.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias High risk

There was a baseline imbalance for lymphadenopathy > 20%. There were no compliance data.

Randomised? Low risk

Quote: "After obtaining the cultures, patients were randomized to..."

Were both inclusion and exclusion criteria specified? High risk

Quote: "We included..." Exclusion criteria was not mentioned.

Dagan 1992

Methods

July 1989 to October 1990; Negev region, Israel; outpatients; only impetigo (bullous and non-bullous)

Participants
  • < 16 years
  • M/F 56/46
  • S. aureus 90/102, streptococci 1/3 of participants

PNE

Interventions
  1. erythromycin susp 50 mg/kg/day 3 td + placebo ointment, 7 days
  2. mupirocin ointment 2% 3 td + oral placebo susp, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "The randomized code was prepared by Beecham Pharmaceutical and was not known to the investigators until after the raw data were tabulated."

Blinding (performance bias and detection bias) Low risk

Quote: "The randomized code was prepared by Beecham Pharmaceutical and was not known to the investigators until after the raw data were tabulated." The erythromycin group received a placebo ointment and the mupirocin group received an oral placebo suspension. The outcome assessor, caregiver, and participant were probably all blinded.

Incomplete outcome data (attrition bias) Low risk

13/102 participants were omitted in the analysis: 8/51 in the erythromycin group (1 due to side-effects, 7 due to refusal to continue treatment or to return for the follow-up visit), 5/51 missing in the mupirocin group (all due to refusal to continue treatment or to return for the follow-up visit).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were age and sex differences at baseline (table 1), although they were not significant. There were no compliance data.

Randomised? Low risk

Quote: "...were randomized into two groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Infants... were enrolled."

Quote: "Excluded groups were..."

Daniel 1991a

Methods

1987 to 1991; Belgium, France, FRG, Netherlands, Norway, UK; setting unclear; range of skin infections (including impetigo 69/308)

Participants
  • 16 to 80 years
  • All participants: S. aureus 195/308, streptococci 59/308

PNE

Interventions
  1. azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days
  2. erythromycin 500 mg 4 td, 7 days
Outcomes

Outcomes of the trial

  1. 11 to 16 days, cured
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were allocated to treatment with azithromycin or erythromycin in a 1:1 ratio using a randomization list."

Allocation concealment (selection bias) Unclear risk

See above - it is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor was likely to also be the caregiver, so probably all 3 were not blinded.

Incomplete outcome data (attrition bias) Low risk

The number of impetigo participants not included in analysis was small and well-balanced (1 vs 2).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data. Baseline characteristics were well-balanced.

Randomised? Low risk

Quote: "Patients were allocated to treatment with azithromycin or erythromycin in a 1:1 ratio using a randomization list."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "In order to be included..."

Quote: "Exclusion criteria were..."

Daniel 1991b

Methods

1987 to 1989; Belgium, Germany, Ireland, UK; setting unclear; range of skin infections (including impetigo 17/323)

Participants
  • Adults 17 to 90 years
  • All participants: S aureus 158/323, streptococci 41/323

PNE

Interventions
  1. azithromycin 250 mg twice (day 1),once daily (day 2 to 5), 5 days
  2. cloxacillin 500 mg, 4 td, 7 days
Outcomes

Outcomes of the trial

  1. 11 to 16 days, cured/improved/failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Using a presupplied randomization list patients were allocated to receive azithromycin or cloxacillin in the ratio of 2:1."

Allocation concealment (selection bias) Unclear risk

See above - it is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

Only 1 impetigo participant was not in the analysis.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data. Baseline characteristics were comparable.

Randomised? Low risk

Quote: "Using a presupplied randomization list patients were allocated to receive azithromycin or cloxacillin in the ratio of 2:1."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "In order to be included..."

Quote: "Exclusion criteria were..."

Demidovich 1990

Methods

Time NR; Honolulu, Hawaii; outpatients; only impetigo

Participants
  • 5 months to 15 years, average 3 years
  • S. aureus 45/73, GABHS 6/73, both 14/73

PNE

Interventions
  1. penicillin V 40 to 50 mg/kg/day in 3 dd, 10 days
  2. cephalexin 40 to 50 mg/kg/day in 3 dd, 10 days
  3. erythromycin 30 to 40 mg/kg/day in 3 dd, 10 days
Outcomes

Outcomes of the trial

  1. 8 to 10 days, failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "The pharmacist randomly assigned them to one of three treatment regimens."

Central allocation - participants could not foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Patients were reevaluated...by one of the authors, both of whom were blinded to the treatment each child was receiving."

Comment: Participants were probably not blinded. The caregiver and outcome assessor were probably blinded.

Incomplete outcome data (attrition bias) Low risk

2/75 participants were omitted in the analysis: 2 participants were lost to follow up (not further specified).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "There was not a significant difference in disease severity among treatment groups." Compliance in both groups was comparable, but low.

Randomised? Low risk

Quote: "The pharmacist randomly assigned them to one of three treatment regimens."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children presenting with impetigo to our pediatric clinic were eligible for the study. Exclusion criteria were..."

Dillon 1983

Methods

1980 summer/fall; Alabama, USA; outpatients; only impetigo (bullous impetigo 57/70)

Participants
  • Average age 3.2 years
  • MF 41/37
  • S. aureus: 64/70

PNE

Interventions
  1. cephalexin 50 mg/kg/day in 2 dd (> 20 kg: 500 mg 2 td)
  2. dicloxacillin 15 mg/kg/day in 4 dd (> 40 kg: 125 mg 4 td)
Outcomes

Outcomes of the trial

  1. Prompt cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were randomly assigned, according to a standard table, to receive..." (Referring to a standard table.)

Allocation concealment (selection bias) Unclear risk

See above - it is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

8/78 participants were omitted in the analysis: 5 vs 3 participants failed to return or, with a negative culture, were not included in the analysis (< 20% and balanced).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "Preference was given to patients with skin infections typical of staphylococcal bullous impetigo." Comment: Furthermore, there were no baseline differences, and compliance was not reported.

Randomised? Low risk

Quote: "Patients were randomly assigned, according to a standard table, to receive..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "The criterion for enrolment was..."

Quote: "...were excluded."

Dux 1986

Methods

Time NR; Toronto, Canada; setting unclear; range of skin infections (including impetigo 36/149)

Participants
  • Average age 22 years
  • M/F 81/68
  • Bacterial culture results unclear

PNE

Interventions
  1. mupirocin ointment 2%, 3 td, 7 days
  2. erythromycin 250 mg, 4 td, 7 days
  3. cloxacillin 250 mg, 4 td, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved/failure.

Clocacillin: no participants with impetigo allocated

Notes

2 cases of secondary impetigo, both in the mupirocin group, were excluded from the results presented here.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information about the sequence generation process was available, and there was unexpected distribution (78 vs 50 vs 20).

Allocation concealment (selection bias) Unclear risk

Quote: "...were randomized into two treatment groups by each investigator."

Comment: It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...single-blind".

Comment: It is not clear who was blinded and how this was done. Also, participants in both groups did not receive the same administrations of study drugs daily. Participants were probably not blinded. The blinding of outcome assessor and caregiver is unclear.

Incomplete outcome data (attrition bias) Low risk

1 (/149) participant was omitted in the analysis: 1/79 in the mupirocin group due to an infected cyst (not included in analysis), 0/50 in the erythromycin group, 0/20 in the cloxacillin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Compliance was not reported. There was a large age difference between groups (mean 22 vs 31 years), unknown for impetigo participants.

Randomised? Low risk

Quote: "In each section of the study, patients with primary or secondary skin infections were randomized into two treatment groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients with primary and secondary skin infections that were severe enough were included in three parallel-study groups."

Quote: "Patient who did not..."

Eells 1986

Methods

October to November 1983; Puerto Rico; outpatients; only impetigo

Participants
  • 7 months to 13 years
  • M/F 13/25
  • Mainly S.aureus

PE

Interventions
  1. mupirocin ointment 2%, 3 td, 7 to 9 days
  2. vehicle control, 3 td, 7 to 9 days
Outcomes

Outcomes of the trial

  1. 8 days, cure/improved/failure

1 participant with ecthyma was excluded in each group.

Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of five per group."

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Low risk

Quote: "...double-blind, vehicle-controlled." Also, participants in both groups received the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably all blinded.

Incomplete outcome data (attrition bias) High risk

14/52 participants were omitted in the analysis: 8/26 in the mupirocin group (5 were "unavailable for follow-up", 3 for several reasons (specified)), 6/26 in the vehicle group (2 were "unavailable for follow-up", 3 for several reasons (specified)). There were more than 20% withdrawals and dropouts.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. Compliance was not reported.

Randomised? Low risk

Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of five per group."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were admitted to the study."

Quote: "Patients were excluded if..."

Esterly 1991

Methods

Time NR; Milwaukee, Wisconsin, USA; outpatients; only impetigo

Participants
  • 3 months to 14 years, average 4.3 years
  • S.aureus 33%; GABHS 12%; both 41%
  • Exclusions: NR
Interventions
  1. mupirocin (dose NR)
  2. erythromycin (dose NR)
Outcomes

Outcomes of the trial

  1. Time of evaluation NR, failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Oral versus topical treatment. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

9/48 participants were omitted in the analysis: 4/25 in the mupirocin group (3 due to "fail to return for follow-up", 1 reason not mentioned), 5/23 in the erythromycin group (3 due to "fail to return for follow-up", 2 reasons not mentioned).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no baseline characteristics per group. There were no compliance data.

Randomised? Low risk

Quote: "...randomized."

Were both inclusion and exclusion criteria specified? High risk

This was not mentioned in the article.

Farah 1967

Methods

Time NR; Lebanon; outpatients; probably all impetigo ('superificial pyogenic skin infection')

Participants
  • 21 days to 60 years of age
  • M/F unknown
  • S. aureus 61%, S. pyogenes 30%
Interventions
  1. gentamycin cream 1% 3 td, duration unknown
  2. neomycin ointment 0.5% 3 td, duration unknown
Outcomes

Outcomes of the trial

  1. Cured, improved after 7 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was provided.

Allocation concealment (selection bias) Unclear risk

This was not reported.

Blinding (performance bias and detection bias) Unclear risk

This was not reported.

Incomplete outcome data (attrition bias) Unclear risk

11/139 participants were lost to follow up (it was not stated in which group).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was an unexplained imbalance of group size (88 vs. 44). There were no compliance data. There was no baseline comparison.

Randomised? Low risk

Quote: "The persons included in this study were divided into two groups at random."

Were both inclusion and exclusion criteria specified? High risk

Inclusion and exclusion criteria was not specified.

Faye 2007

Methods

2002 to 2003; Mali; hospital outpatients; only impetigo

Participants
  • Inclusion > 1 year of age
  • Mean age 8.5 years
  • M/F 74/58
  • No bacteriological investigation
Interventions
  1. oral amoxicillin 50 mg/kg/day + topical 10% povidone iodine for 7 days
  2. oral erythromycin 30 mg/kg/day + topical 10% povidone iodine for 7 days
Outcomes

Outcomes of the trial

  1. Proportion cured + improved after 7 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "...using a table of random numbers".

Comment: This was an adequate method.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) High risk

Quote: "....an open randomized trial."

Quote: "Patients and investigators were not blinded." The outcome assessor, participant, and caregiver were not blinded.

Incomplete outcome data (attrition bias) Low risk

3/132 participants were not analysed: 2/66 in the amoxicillin group (2 lost to follow up on the 7th day), 1/66 in the erythromycin group (1 lost to follow up on the 7th day).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline comparison. There were no compliance data.

Randomised? Low risk

Quote: "...an open randomized trial."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients aged more than 1 year old... were considered for inclusion."

Quote: "The following cases were excluded..."

Fujita 1984

Methods

Time NR; Japan; outpatients; range of skin infections (including impetigo 10/204)

Participants
  • Age 16 to 84 years
  • M/F 120/84 (all participants)
Interventions
  1. enoxacin 500 mg 3 td
  2. cephalexin 500 mg 2 td
(double dummy)
Outcomes

Outcomes of the trial

  1. After .... cured/improved
Notes

Secondary impetigo- it only says impetigo above

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not mentioned in the abstract.

Allocation concealment (selection bias) Unclear risk

This was not mentioned in the abstract.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...a double-blind." They used placebo capsules (see Figure 1 Dosage schedule). Participants were probably blinded. It is not clear how, and if, the caregiver and outcome assessor were blinded.

Incomplete outcome data (attrition bias) Unclear risk

22/226 participants were omitted in the analysis: 14/115 in the enoxacin group (2 due to exclusion (1 overlap administration and 1 antibiotics before treatment), 12 dropped out (11 shortage of duration, 1 no successive visit)), 8/111 in the cephalexin group (all dropped out (7 shortage of duration, 1 no successive visit). < 20% but not specified for impetigo participants.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance (table 4), and compliance was not reported.

Randomised? Unclear risk

This was not mentioned in the abstract.

Were both inclusion and exclusion criteria specified? Unclear risk

This was not mentioned in the abstract.

Gilbert 1989

Methods

Time NR; Quebec, Canada; outpatients; range of skin infections (including impetigo 19/70)

Participants
  • Age NR
  • S. aureus 41/70; Streptococci 22/70 (all participants)

PE

Interventions
  1. mupirocin ointment 2%, 3 td, 7 days
  2. fusidic acid cream 2%, 3 td, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved/failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

The abstract reported the study was double-blind, but it is not explained in the article. There is unclear blinding of the outcome assessor, caregiver, and participant.

Incomplete outcome data (attrition bias) Low risk

1 (/70) participant was omitted in the clinical analysis: 0/35 in the fusidic acid group, 1/35 in the mupirocin group. Participants were not examined if pre-treatment cultures were negative or if post-treatment evaluation was not possible.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance, and compliance was not reported.

Randomised? Low risk

Quote: "Patients were randomly divided into two treatment groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients who... were excluded from the trial."

Quote: "...in 70 patients who came to the dermatologic clinic with primary and secondary skin infections of sufficient severity to require antibiotic therapy."

Ginsburg 1978

Methods

Time NR; Dallas, Texas, USA; outpatients; only impetigo

Participants
  • 8 months to 8 years, average 3.1 years
  • Sex NR
  • S.aureus 78%, GABHS 64%, both 50%

Part excluded: unclear

Interventions
  1. penicillin G 30 mg/kg/day in 4 dd, duration NR
  2. cefadroxil 45 mg/kg/day in 3 dd, duration NR
Outcomes

Outcomes of the trial

  1. 8 days, cured + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Participants in both groups received different administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) High risk

21/71 participants were omitted in the analysis due to failure to return for both follow-up examinations. There were more than 20% withdrawals; this was not further specified for each group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "Groups were comparable with regard to age, sex, race and extent of skin lesion." Compliance was unclear.

Randomised? Low risk

Quote: "Infants and children with impetigo were assigned treatment randomly."

Were both inclusion and exclusion criteria specified? High risk

Quote: "Infants and children with impetigo were assigned..." No exclusion criteria were specified.

Giordano 2006

Methods

2005; US; hospital outpatients; skin infections (including impetigo 16/391)

Participants
  • All diagnoses: 13 to 93 years
  • M/F 206/185
  • S. aureus 44%; S. pyogenes 2%
Interventions
  1. oral cefdinir 300 mg 2 td 10 days
  2. cephalexin 200 mg 4 td 10 days
Outcomes

Outcomes of the trial

  1. Proportion cured + improved after 17 to 24 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "A computer-generated randomization schedule in a 1:1 ratio was used."

Quote: "Study drug containers were dispensed in increasing numerical sequence at each investigative site."

Allocation concealment (selection bias) Unclear risk

Quote: "To maintain investigator blinding, the study drug was dispensed by an unblinded third person who did not participate in the assessments of clinical response."

Comment: It is not clear whether this person was involved in participant contacts.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...investigator-blinded."

Quote: "To maintain investigator blinding, the study drug was dispensed by an unblinded third person who did not participate in the assessments of clinical response. Furthermore, the participant was instructed not to disclose any details about the study drug (...) to the investigator." The outcome assessor and caregiver were blinded. The participants were not blinded.

Incomplete outcome data (attrition bias) Low risk

There were 0/16 missing impetigo participants: 0/4 in the cefdinir group, 0/12 in the cephalexin group. All 391 who took at least 1 dose of the study drug were analysed.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data. There was no baseline comparison.

Randomised? Low risk

Quote: "A computer-generated randomization schedule..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were enrolled"

Quote: "Study exclusion criteria included..."

Goldfarb 1988

Methods

Time NR; Cleveland, Ohio, USA; outpatients; only impetigo

Participants
  • 5 months to 13 years, average 3.8
  • M/F 31/31
  • S.aureus 49/62, Streptococci 4/62, both 9/62

PE: NR

Interventions
  1. mupirocin ointment 2%, 3 td, 8 days
  2. erythromycin 40 mg/kg/day in 4 dd, 8 days
Outcomes

Outcomes of the trial

  1. 8 days, cured/failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Topical versus oral treatment. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

10/62 participants were lost in total: 5/30 in the mupirocin group (all lost to follow up), 5/32 in the erythromycin group (all lost to follow up).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

The severity of impetigo was not compared between the 2 groups. There was a difference in age (range vs mean). Compliance was not reported.

Randomised? Low risk

Quote: "Enrolled children were randomly assigned to groups that..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children 3 months of age and older were seen at...were eligible for our study."

Quote: "Children were excluded if..."

Gonzalez 1989

Methods

July to September 1980; Florida, USA; outpatients; only impetigo (bullous and non-bullous).

Participants
  • 6 months to 12 years

Participants were excluded if no S. aureus was present

Interventions
  1. penicillin V potassium 50 mg/kg/day, in 4 dd, 10 days
  2. cloxacillin sodium 50 mg/kg/day, in 4 dd, 10 days
Outcomes

Outcomes of the trial

  1. 10 days: cured + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "...on a randomized schedule at the following dosages". It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

Quote: "The clinical examiners were blinded to the antibiotic that the patients received until the study was concluded."

Quote: "...double-blind schedule." It is not clear how patients were blinded, and the participant was likely to be influenced in the case of lack of blinding. The outcome assessor and caregiver were blinded. 

Incomplete outcome data (attrition bias) High risk

24/101 participants were lost due to no S. aureus growth, 10 were lost in failure to return to the clinic (reasons for not attending follow-up visit were not stated). The imbalance in participants was not evaluated.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline severity comparison between groups. Participant compliance data was computed and presented no significant alterations in therapeutic outcome.

Randomised? Low risk

Quote: "...on a randomized schedule at the following dosages..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...could be enrolled on the study if the following criteria were met..."

Quote: "There were no prior histories of allergic phenomena."

Gould 1984

Methods

Time NR; Edinburgh, UK; general practice; range of skin infections (including impetigo 39/107)

Participants
  • Average age 18.7 (all participants)
  • S. aureus 90/129, streptococci 32/129 (all participants)

PNE

Interventions
  1. mupirocin ointment 2%, once daily, until cleared
  2. placebo cream, once daily, until cleared
Outcomes

Outcomes of the trial

  1. Time of evaluation NR, cure/improved/failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Quote: "Patients were allocated a trial number in the consecutive order of their entry in the study. The study was performed under double blind conditions. Medication appropriate to the trial number, either mupirocin or placebo ointment, was dispensed according to a pre-determined randomization which ensured that in each group of four patients, two received treatment with mupirocin and two with placebo ointment." The process for selecting the blocks was not specified.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "The study was performed under double-blind conditions." It is unclear whether, and how, the outcome assessor, caregiver, and participant were blinded.

Incomplete outcome data (attrition bias) Unclear risk

14/107 participants were omitted in the analysis: 10/54 in the mupirocin group (they were classified as clinically unassessable, 7 did not return for final assessment (5 were traced later and found to have clinically improved), 3 developed other diseases requiring systemic treatment), 4/53 in the placebo group (3 did not return for final assessment (2 of whom were later found to have improved and one worsened and sought alternative treatment), 1 developed other disease requiring systemic treatment). < 20%, 3 vs 1 impetigo participant not evaluable.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "...well matched". There was no compliance data.

Randomised? Low risk

Quote: "...according to a pre-determined randomization."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients with acute primary skin infections...who had not received topical or systemic antibiotics during the preceding 3 days were entered in the study."

Gratton 1987

Methods

Time NR; Montreal, Quebec, Canada; outpatients; range of skin infections (including impetigo 15/60)

Participants
  • Age/sex NR
  • S. aureus approx 50%

PE: NR

Interventions
  1. mupirocin ointment 2%, 3 td, 7 days
  2. erythromycin 250 mg, 4 td, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved/failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "...were randomly divided into two treatment groups." It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Topical versus oral treatment. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

0/60 participants were omitted in the analysis: 0/30 in the mupirocin group, 0/30 in the erythromycin group. 1 participant in the mupirocin group discontinued therapy due to intolerable side-effects. All impetigo participants were included in the analysis.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline data. There were no compliance data.

Randomised? Low risk

Quote: "...were randomly divided into two treatment groups."

Were both inclusion and exclusion criteria specified? High risk

Quote: "Sixty patients with primary and secondary skin infections were randomly divided." No exclusion criteria was specified.

Hains 1989

Methods

Summer 1986; Birmingham, Alabama, US; outpatients child hospital; only impetigo

Participants
  • 1 to 18 years
  • Sex NR
  • S. aureus 35%, GABHS 12%, both 54%

PE: NR

Interventions
  1. cefadroxil 30 mg/kg/day, max 1 g, in 1 dd, 10 days
  2. cephalexin 30 mg/kg/day, max 1 g, in 2 dd, 10 days
Outcomes

Outcomes of the trial

  1. 14 days, cured
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "Patients were randomly assigned to receive either..." It is unclear whether participants and investigators enrolling patients could foresee assignment.

Blinding (performance bias and detection bias) High risk

Participants in both groups received different administrations of study drugs daily. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

13/101 participants were omitted in the analysis in total: 4/55 in the cefadroxil group (1 failed to keep all of the appointments, 3 participants failed to take medications as prescribed), 9/54 in the cephalexin group (3 with negative cultures, 4 failed to keep all of the appointments, 2 participants failed to take medications as prescribed). < 20% and reasons described.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was baseline data. Compliance was good in both groups.

Randomised? Low risk

Quote: "Patients were randomly assigned to receive either..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...who had a clinical diagnosis of pyoderma were enrolled."

Quote: "Children were excluded if..."

Ishii 1977

Methods

Summer 1976; Tokyo, Japan; hospital outpatient clinic; bullous impetigo

Participants
  • 0 to 10 years
  • M/F 26/34
  • No bacterial investigations
  • All participants evaluable
Interventions
  1. topical Eksalbe simplex (ointment containing killed escherichia, staphylococcus, streptococcus, and pseudomonas) applied once daily under plaster or 3 times daily without plaster
  2. placebo
Outcomes

Outcomes of the trial

  1. Cured/improved after 4 days
Notes

Data extraction and risk of bias assessment done by Testuri Matsumura.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not reported.

Allocation concealment (selection bias) Low risk

Allocation was concealed (assessed by Tetsuru Matsumura).

Blinding (performance bias and detection bias) Low risk

The participant, outcome assessor, and caregiver were blinded.

Incomplete outcome data (attrition bias) Low risk

2/40 participants were dropouts and excluded from the analysis.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data.

Randomised? Low risk

This trial was randomised (assessed by Tetsuru Matsumura).

Were both inclusion and exclusion criteria specified? High risk

Exclusion criteria were not specified.

Jaffe 1985

Methods

Time NR; Cleveland, Ohio, USA; outpatients child clinic; range of skin infections (including impetigo 32/42)

Participants
  • 6 months to 12 years, average 4.8 years
  • S. aureus 33/36, S. pyogenes 8/36

PNE

Interventions
  1. amoxicillin/clavulanic (125/30) acid, dose equivalent to 20 mg amoxicillin/kg/day in 3 dd, 10 days
  2. cefaclor 20 mg/kg/day in 3 dd
Outcomes

Outcomes of the trial

  1. 10 days, cured/failed
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "Prescription were filled by the hospital pharmacist using double-blind labels." Personnel or participants could, probably, not foresee assignment.

Blinding (performance bias and detection bias) Low risk

Quote: "Prescription were filled by the hospital pharmacist using double-blind labels." The outcome assessor, caregiver, and participant were probably all blinded.

Incomplete outcome data (attrition bias) Low risk

0/43 participants were omitted in the analysis: 0/21 in the amoxicillin/clavulanic acid group, 0/22 in the cefaclor group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Low risk

Quote: "The two treatment groups were generally comparable." Compliance was good in 75% of participants.

Randomised? Low risk

Quote: "Children were randomly assigned to one of the two treatment regimens."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children 6 months to...were eligible for inclusion in the study."

Quote: "Exclusion criteria included..."

Jaffe 1986

Methods

Time NR; multicentre, Wessex, UK; general practice; range of skin infections (including impetigo 43/119)

Participants
  • 2.5 years to 83 years, median 14 to 16 years
  • M/F 23/20
  • S. aureus 16/34, S. pyogenes 5/34

PNE

Interventions
  1. 1% hydrocortisone + 0.5% potassium hydroxyquinoline sulphate cream, 2 td, 14 days
  2. 1% hydrocortisone + 2% miconazole nitrate cream, 2 td, 14 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "The trial was double-blind, patients being allocated at random to receive..."

Quote: "The randomization was balanced for each centre, with separate randomizations for each of the two indications." It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) Low risk

Quote: "Unmarked plain tubes of the marketed formulation of each product were packed in plain sealed cartons, neither doctors nor patients being aware of the identity of the products until the end of the study."

Comment: The outcome assessor, caregiver, and participant were probably blinded.

Incomplete outcome data (attrition bias) Low risk

0/119 participants were omitted in the analysis: 0/65 in group 1, 0/54 in group 2.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Details of age, duration of condition, and total symptom severity score were recorded and were similar. There were no compliance data.

Randomised? Low risk

Quote: "The trial was double-blind, patients being allocated at random to receive..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...who presented... were included in the study." Exclusion criteria was not specified.

Kennedy 1985

Methods

Time NR; Bristol, UK; general practice; only impetigo

Participants
  • Average age 11 years (mupirocin), 17 years (neomycin)
  • M/F 2/1
  • S. aureus 23/34, S. pyogenes 10/34

PNE

Interventions
  1. mupirocin ointment 2%, 2 td, 10 to 11 days
  2. neomycin ointment 1%, 2 td, 10 to 11 days
Outcomes

Outcomes of the trial

  1. Time of evaluation NR, cure/improved/failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Quote: "Allocation of treatment was on a randomized basis. In each consecutive group of four patients, two received Bactroban ointment and two received neomycin."

Comment: They probably used blocked randomisation, but the process of selecting the blocks was not specified.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

Quote: "The 15-g tubes differed only in their code numbers and in both cases the content was a white ointment." It is unclear how investigators were blinded. The caregiver and participant were probably blinded.

Incomplete outcome data (attrition bias) Low risk

9/41 participants were omitted in the analysis: 8 were excluded due to a "stated diagnosis other than uncomplicated impetigo" (not stated which group), 1 missing from the mupirocin group due to "failure to attend to follow-up".

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was baseline imbalance for age (mean 11 vs 17 years). There were no compliance data.

Randomised? Low risk

Quote: "Allocation of treatment was on a randomized basis."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients were selected from those presenting with typical impetigo."

Quote: "Patients were excluded if..."

Kiani 1991

Methods

Time NR; multicentre USA (Southern States); admitted + outpatients; range of skin infections (including impetigo 18/179)

Participants
  • Age > 16, 211/154 (all participants)
  • S. aureus 152/179, S. pyogenes 29/179 (all participants)

PE

Interventions
  1. azithromycin 500 mg day 1, 250 mg, day 2 to 5, 5 days
  2. cephalexin 500 mg twice daily, 10 days
Outcomes

Outcomes of the trial

  1. 11 days, cured/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "In this double blind..."

Quote: "Using a double-dummy technique, each patient received placebo capsules which were visually identical to the active drugs."

Comment: The caregiver and participant were probably blinded. There was unclear blinding of the outcome assessor.

Incomplete outcome data (attrition bias) High risk

187/366 participants were omitted in the analysis: 99/182 in the azithromycin group (58 due to "no baseline pathogen", 15 due to "no end of therapy assessment", 15 due to "the presence of a resistant pathogen" (only main reasons mentioned)), 88/184 in the cephalexin group (55 due to "no baseline pathogen", 6 due to "no end of therapy assessment", 6 due to "the presence of a resistant pathogen" (main reasons mentioned)). > 20% no end of therapy assessment (not specified for impetigo only).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was a baseline comparison for sex, race, and primary diagnosis. There was no baseline imbalance. There were no compliance data.

Randomised? Low risk

Quote: "Patients were randomly assigned in a double-blind fashion to one of the two treatment groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients were entered in the study based on..."

Quote: "...were excluded by the protocol."

Koning 2003

Methods

February 1999 to November 2000; Rotterdam, Netherlands; general practice; only impetigo

Participants
  • < 12, average age 5.0 years
  • M/F 98/62
  • S. aureus 127/160, S. pyogenes 5/160, both 8/160, none 20/160

PNE

Interventions
  1. fusidic acid cream 2%, 3 td + povidone iodine shampoo, 2 td
  2. placebo cream, 3 td + povidone iodine shampoo, 2 td
Outcomes

Outcomes of the trial

  1. 7 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "An independent statistician provided a computer-generated list of random set numbers in permuted blocks of six. The hospital pharmacist packed the study medication in identical blank tubes with a number according to the randomisation list."

Allocation concealment (selection bias) Low risk

See above - probably done: central allocation.

Blinding (performance bias and detection bias) Low risk

Quote: "Unblinding took place after the primary statistical analysis had been done."

Quote: "....research nurse was unaware of treatment allocation."

Quote: "...placebo cream did not differ."

Quote: "Unblinding took place after the primary statistical analysis had been done."

Comment: The outcome assessor, caregiver, and participant were probably all blinded.

Incomplete outcome data (attrition bias) Low risk

4/160 participants were omitted in the analysis (after 1 week): 2/78 in the fusidic acid cream group (both did not want to follow up), 2/82 in the placebo cream group (both did not want to follow up).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. There was more non-compliance in the placebo group.

Randomised? Low risk

Quote: "Patients were randomised blockwise."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "General practitioners (GP's) in the Greater Rotterdam were asked to report patients aged 0-12 years with nonbullous impetigo presenting at their surgery."

Quote: "Exclusion criteria were..."

Koning 2008

Methods

April to December 2005; India, Mexico, Netherlands, Peru; hospital outpatients and general practice patients; only impetigo

Participants
  • 0 to 73 years of age, mean age around 11 years
  • M/F 107/103
  • S. aureus 146/210, S. pyogenes 42/210
Interventions
  1. topical retapamulin 1% 2 td for 5 days
  2. topical placebo 2 td for 5 days
Outcomes

Outcomes of the trial

  1. Cured or improved after 7 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "Randomization was centre based and performed using an automated telephone system."

Blinding (performance bias and detection bias) Low risk

Quote: "The packaging and labelling of study medication was identical for the active medication and its placebo counterpart. All efforts were made to make the study medication and placebo identical with respect to appearance and smell." The outcome assessor, caregiver, and participant were all blinded.

Incomplete outcome data (attrition bias) High risk

50/213 participants missing in total: 18/140 in the retapamulin group (1 did not receive intervention, 17 withdrawals (5 lack of efficacy, 3 disease progression, 2 decided to withdraw, 1 adverse event, 5 lost to follow up)), 33/73 in the placebo group (2 did not receive intervention, 31 withdrawals (18 lack of efficacy, 9 disease progression, 1 adverse event, 3 lost to follow up)). > 20% missing data.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "The mean total lesion area at baseline was larger in the retapamulin group compared with the placebo group." There was an imbalance for age. There were no compliance data.

Randomised? Low risk

Quote: "We carried out a randomized..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Inclusion criteria were..."

Quote: "...were excluded."

Koranyi 1976

Methods

1974; Columbus, Ohio, USA; outpatients; only impetigo

Participants
  • 2 months to 15 years
  • M/F 14/16
  • S. aureus 22/30, S. pyogenes 10/30

PNE

Interventions
  1. bacitracin ointment 500 units/g, 4 td + oral placebo 6 days
  2. erythromycin 250 mg 4 td + placebo cream, 6 days
Outcomes

Outcomes of the trial

  1. 6 days, cured/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Drug assignment was based on a random distribution table, without the knowledge of the authors."

Allocation concealment (selection bias) Low risk

See above.

Blinding (performance bias and detection bias) Low risk

See above. Also double dummy design. The outcome assessor, caregiver, and participant were all blinded.

Incomplete outcome data (attrition bias) Low risk

0/30 participants were omitted in the analysis: 0/15 in the bacitracin group, 0/15 in the erythromycin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline comparison for the most important prognostic factors. There were no compliance data.

Randomised? Low risk

Quote: "Drug assignment was based on a random distribution table, without the knowledge of the authors."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were enrolled in the study."

Quote: "...were excluded."

Kuniyuki 2005

Methods

2002 to 2003; Japan; hospital outpatients; only impetigo

Participants
  • 2 months to 13 years
  • M/F 27/22
  • S. aureus 49/49 (inclusion criterion)
Interventions
  1. topical tetracycline 3% 3 td + oral cefdinir 9 mg/kg/day for 7 days
  2. topical tetracycline 3% 3 td + oral minomycin 4 mg/kg/day for 7 days
  3. topical tetracycline 3% 3 td + oral fosfomycin 40 mg/kg/day for 7 days
  4. topical tetracycline 3% 3 td for 7 days
Outcomes

Outcomes of the trial

  1. Cured, improved after 7 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not reported.

Allocation concealment (selection bias) Unclear risk

This was not reported.

Blinding (performance bias and detection bias) High risk

Quote: "...open-label." The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) Unclear risk

Only participants who were culture positive were analysed. The number of dropouts and withdrawals was not mentioned.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no compliance data. There was a baseline comparison for age and sex - no imbalance.

Randomised? Low risk

Quote: "...randomized".

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were admitted to the study."

Quote: "We excluded patients..."

McLinn 1988

Methods

February to May 1986 ; Scottsdale, Arizona, USA; outpatients; only impetigo

Participants
  • > 6 months, average 5.5 years
  • S.aureus 43/60, S.pyogenes 17/60

PE

Interventions
  1. mupirocin ointment 2%, 3 td, 7 to 9 days
  2. erythromycin 30 to 40/mg/kg/day in 3 to 4 doses, 7 to 9 days
Outcomes

Outcomes of the trial

  1. 8 to 12 days, very much improved/ improved/no change
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of four."

Allocation concealment (selection bias) Low risk

Quote: "...investigator was blinded to the treatment the patient was to receive at the time of patient entry."

Blinding (performance bias and detection bias) High risk

Quote: "The investigator was blinded to the treatment the patient was to receive at the time of patient entry and was unblinded only in those cases where lesions persisted requiring additional culturing." Quote: "...open-label". This was not blinded for all participants. Also topical versus oral treatment. The outcome assessor and caregiver were not blinded.

Incomplete outcome data (attrition bias) Low risk

0/60 participants were omitted in the analysis for clinical efficacy: 0/30 in the mupirocin group, 0/30 in the erythromycin group (2 participants in the erythromycin group discontinued therapy because of severe adverse experiences).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was a severe baseline imbalance, more fever in erythromycin group (12 versus 3), but they seem to have adjusted for this in the analysis. There were no compliance data.

Randomised? Low risk

Quote: "Patients were randomized between the two treatment groups by a computer-generated set of random numbers in blocks of four."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...were enrolled in the study."

Quote: "Patients with...were excluded."

Mertz 1989

Methods

Time NR; San Juan, Puerto Rico; outpatients; only impetigo

Participants
  • 6 months to 32 years, average 5.4 years
  • M/F 27/26; S.aureus 44/53, GABHS 37/53

PE

Interventions
  1. mupirocin ointment 2%, 3 td, 7 to 9 days
  2. erythromycin 30 to 50 mg/kg/day in 2 doses, 7 to 9 days
Outcomes

Outcomes of the trial

  1. 7 to 9 days, cured/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were randomized between the two treatment groups according to a computer-generated schedule having a block size of four."

Allocation concealment (selection bias) Low risk

See above, and Quote: "The randomization was predetermined by the sponsor and the schedule for distribution of medications was entrusted to a team member whose assignment was to dispense medication."

Blinding (performance bias and detection bias) Unclear risk

Quote: "...were examined in a investigator-blinded study."

Quote: "The randomization was predetermined by the sponsor and the schedule for distribution of medications was entrusted to a team member whose assignment was to dispense medication." Also, there was treatment with ointment versus capsules. The outcome assessor was blinded. The caregiver and the participant were not blinded.

Incomplete outcome data (attrition bias) High risk

22/75 participants were omitted in the analysis: 9 were missing in the mupirocin group (unclear why), 13 were missing in the in the erythromycin group (unclear why).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was an imbalance for sex: 17/28 versus 10/25 boys (assessable participants) = 61% vs 40%. There was no compliance data.

Randomised? Low risk

Quote: "Patients were randomized between the two treatment groups according to a computer-generated schedule having a block size of four."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients 3 months of age and older of either sex who had no more than seven lesions of impetigo, cellulitis, abscesses, or furunculosis were admitted to the study."

Montero 1996

Methods

Time NR; multicentre; Columbia Guatemala, Panama, South Africa; outpatients; range of skin infections (including impetigo 95/200)

Participants
  • 6 months to 12 years
  • M/F 101/94 (all participants)
  • S.aureus 109/200, S.pyogenes 39/200

PNE

Interventions
  1. azithromycin susp 10 mg/kg/day once daily, 3 days
  2. cefaclor susp 20 mg/kg/day in 3 doses, 10 days
Outcomes

Outcomes of the trial

  1. 10 to 14 days, cured + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Quote: "Patients were randomly assigned in a 1:1 ratio to receive either..." It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Quote: "This open, comparative study..." Participants in both groups did not receive the same administrations of study drugs daily.

Comment: The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

4/100 participants were omitted in the analysis (all attritions): 2/100 in the azithromycin group (due to loss of follow up), 2/100 in the cefaclor group (due to loss of follow up).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance for gender, age, weight, height, and ethnic origin. There were no compliance data.

Randomised? Low risk

Quote: "Patients were randomly assigned in a 1:1 ratio to receive either..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Two hundred children...entered this multicentre..."

Quote: "Patients were excluded from the study if...shown in Table I."

Moraes Barbosa 1986

Methods

Time NR; Rio de Janeiro, Brasil; hospital outpatients; only impetigo

Participants
  • Newborns, age 3 to 14 days, average 11 days
  • M/F 25/23
  • S.aureus 100% (required for inclusion)
Interventions

4 arms:

  1. sodium fusidate ointment 2%, 3 td, 10 days
  2. chloramphenicol ointment, 3 td, 10 days
  3. neomycin/bacitracin ointment, 3 td, 10 days
  4. erythromycin oral 50 mg/kg/day, in 4 dd, 10 days
Outcomes

Outcomes of the trial

  1. 7 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) High risk

Oral versus topical treatment. The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) Low risk

All 48 participants were analysed (see table 2).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no differences for sex. No other characteristics were reported. There were no compliance data.

Randomised? Low risk

Quote: "Estes foram divididos aleatoriamente em quatro grupos de 12." [They were randomly divided in 4 groups of 12.]

Were both inclusion and exclusion criteria specified? High risk

Quote: "Quarenta e oito recem-nascidos entre tres e 14 dias de idade, portadores de impetigo estafilococico sem tratamento topica ou oral anterior, foram incluidos neste estudo." [40 and 8 neonates between 3 and 14 days old, who were carriers of impetigo stafylococcus without previous topical or oral treatment, had been enclosed in this study.] No exclusion criteria was specified.

Morley 1988

Methods

Time NR; Plymouth/Bristol, UK; general practice; range of skin infections (including impetigo 89/354)

Participants
  • 1 to 92 years, average 33 years (all participants)
  • M/F 162/192 (all participants)
  • S.aureus 119/344, S.pyogenes 15/344, both 25/344 (all participants)

PNE

Interventions
  1. fusidic acid ointment 2%, 3 td, up to 7 days
  2. mupirocin ointment 2%, 3 td, up to 7 days
Outcomes

Outcomes of the trial

  1. 6 to 8 days, excellent/good
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "On entry, patients were allocated at random to receive one or other treatment, tubes of the ointment being provided in plain sealed numbered containers so that the investigator was unaware of the treatment given."

Comment: This was probably done.

Blinding (performance bias and detection bias) Unclear risk

Quote: "On entry, patients were allocated at random to receive one or the other treatment, tubes of the ointment being provided in plain sealed numbered containers so that the investigator was unaware of the treatment given."

Comment: The participants were probably blinded because the tubes were plain sealed. The outcome assessor was blinded. It is unclear whether the caregiver was blinded (it is unclear if the outcome assessor was also the caregiver).

Incomplete outcome data (attrition bias) Low risk

0/354 participants were omitted in the analysis: 0/191 in the sodium fusidate group, 0/163 in the mupirocin group. Therapy was withdrawn in only 2 cases - 1 in each treatment group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was baseline comparison for sex, age, and severity. There were no compliance data.

Randomised? Low risk

Quote: "On entry, patients were allocated at random to receive one or other treatment."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "The study involved 354 patients with acute superficial skin sepsis amenable to therapy with a topical antibiotic."

Quote: "Patients who...were excluded."  

Quote: "...were also exclusion factors."

Nolting 1988

Methods

Time NR; Münster, Germany; outpatients; range of skin infections (including impetigo 66/80)

Participants
  • 1 to 65 years, average 24 years
  • M/F 35/31
  • S.aureus 41/66, GABHS 8/66, both 17/66

PE

Interventions
  1. sulconazole nitrate cream 1%, 2 td, 14 days
  2. miconazole nitrate cream 2%, 2 td, 14 days
Outcomes

Outcomes of the trial

  1. 7 days/14 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "When patients enrolled in the trial, they were allocated, according to a computer-generated randomization code, to receive either..."

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...double-blind, parallel comparative study". It is unclear if, and how, the outcome assessor, caregiver, and participant were blinded.

Incomplete outcome data (attrition bias) Low risk

0/80 participants were omitted in the analysis: 0/40 in the sulconazole group, 0/40 in the miconazole group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

The proportion of micro-organisms isolated at admission differs between groups (19 vs 6 for streptococcus, 53 vs 71 for S. aureus). There were no compliance data.

Randomised? Low risk

Quote: "...according to a computer-generated randomization code..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients...were admitted to the trial."

Quote: "...were excluded from the trial."

Oranje 2007

Methods

2005; Canada, Costa Rica, France, Germany, India, The Netherlands, Peru, Poland, South Africa; outpatients; only impetigo

Participants
  • 9 months to 84 years
  • M/F 278/239
  • S. aureus 341/517, S. pyogenes 137/517
Interventions
  1. topical retapamulin 1% 2 td for 5 days
  2. topical sodium fusidate 2% 3 td for 7 days
Outcomes

Outcomes of the trial

  1. Cure or improvement after 7 (retapamulin) or 9 days (sodium fusidate)
Notes

Randomisation was 2:1.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

This was not reported.

Allocation concealment (selection bias) Low risk

Quote: "...predetermined, center-based 2:1 schedule using the telephone-based interactive, central Registration and Medication Ordering System."

Blinding (performance bias and detection bias) Unclear risk

Quote: "...observer-blinded..."

Quote: "...helped protect investigator blinding."

Quote: "To maintain observer blinding..." Participants in both groups did not receive the same administrations of study drugs daily. Participants were not blinded, the outcome assessor was blinded, and the blinding of the caregiver is unclear

Incomplete outcome data (attrition bias) Low risk

41/519 participants were missing data in both groups: 26/346 in the retapamulin group (26 prematurely discontinued, of which 8 had disease progression, 8 were lost to follow up, 1 had adverse events, 1 through lack of efficacy, 1 through protocol violation, 1 through potential conflicts of interest, 3 through 'other'), 15/172 in the sodium fusidate group (15 prematurely discontinued, of which 6 had disease progression, 1 was lost to follow up, 1 through subject decision [participant decision?], 3 had adverse events, 1 through lack of efficacy, 3 through 'other'), 1/519 were not included in the analysis.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. Compliance was comparable.

Randomised? Low risk

Quote: "This was a randomised..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Subjects were included if..."

Quote: "Subjects were excluded if..."

Pruksachat 1993

Methods

December 1988 to November 1990; Chiang Mai, Thailand; outpatients; only impetigo

Participants
  • 1 months to 8 years, median 3.5 years
  • M/F 64/46 (all participants)
  • S. aureus 77/110

PE

Interventions
  1. penicillin V potassium 50 mg/kg/day in 4 doses, 7 days
  2. cloxacillin sodium 50 mg/kg/day in 4 doses, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure
Notes

Bullous and non-bullous impetigo.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

This was not mentioned in the article: If the outcome assessor, caregiver, or participant was not blinded, he or she is likely to cause bias. All 3 were probably not blinded.

Incomplete outcome data (attrition bias) High risk

20/110 participants were omitted in the analysis: 45 were treated in the penicillin group and 45 were in the cloxacillin group (9 were unavailable for follow-up and 11 were negative to culture - not specified per group).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no baseline characteristics per group. There were no compliance data.

Randomised? Low risk

Quote: "Participants were randomly assigned to receive either..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children... were invited to participate in the study."

Quote: "Inclusion criteria included..."

Rice 1992

Methods

April to November 1989; Baltimore, USA; outpatients and general practice; only impetigo

Participants
  • 3 months to 16 years
  • MF 53/30
  • Culture only in case of therapy failure

PNE

Interventions
  1. erythromycin ethynyl succinate 40 mg/kg/day in 4 doses, 10 days
  2. mupirocin ointment 2%, 3 td, 10 days
Outcomes

Outcomes of the trial

  1. 9 to 11 days, cure/improved/failure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) High risk

Quote: "In any clinical trial that is not blinded..." Also, oral versus topical treatment. The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) Low risk

10/93 participants were omitted in the analysis. The following were specified: 4/46 in the erythromycin group (4 did not return for follow-up), 6/47 in the mupirocin group (4 did not return for follow-up, 2 were excluded from completing the protocol, 1 had cellulites develop within a few hours after entry into the study, 1 whose primary provider added an oral antibiotic to the treatment regimen on day 3 of therapy even though the participant's condition was improving).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Low risk

The baseline characteristics were comparable. Compliance was good and comparable (table 6).

Randomised? Low risk

Quote: "Children were randomly assigned to the two study groups."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "All children... were invited to participate."

Quote: "Exclusion criteria included..."

Rist 2002

Methods

Time NR; USA; outpatients; secondary impetigo (all eczema)

Participants
  • 9 to 87 years
  • M/F 87/72
  • S. aureus 74/159, S. pyogenes 0/159
Interventions
  1. topical mupirocin 2% 3 td + oral placebo for 10 days
  2. oral cephalexin 250 mg 4 td + topical placebo for 10 days
Outcomes

Outcomes of the trial

  1. Cured or improved after 12 to 13 days
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Low risk

Quote: "...double-blind, double-dummy, parallel-group trial..." The outcome assessor, caregiver, and participant were all blinded.

Incomplete outcome data (attrition bias) High risk

33/159 (> 20%) participants did not complete the study (not specified per group). All 159 were in the ITT analysis. Participants whose outcome was indeterminable were considered failures. This may have introduced bias.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "Compliance was similar for both groups."

Quote: "The mean SIRS scores were 20.5 for the mupirocin group and 19,1 for the cephalexin group (P = 0.09)." There was an imbalance for sex.

Randomised? Low risk

Quote: "In this randomized..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Patients were eligible for entry into the trial if..."

Quote: "Patients were excluded from the study if..."

Rodriguez-Solares 1993

Methods

Time NR; multicentre; Costa Rica, Guatemala, Panama, Venezuela; outpatients; range of skin infections (including impetigo 39/118)

Participants
  • 2 to 12 years, mean 5 years
  • M/F NR
  • S. aureus 69/118, S. pyogenes 9/118 (all participants)

PNE

Interventions

3 arms:

  1. azithromycin 10 mg/kg/day (max. 500), once daily, 3 days
  2. dicloxacillin12.5 to 25 mg/kg/day in 4 doses, 7 days (see notes)
  3. flucloxacillin 500 to 2000 mg/day in 4 doses (see notes)
Outcomes

Outcomes of the trial

  1. 7 to 10 days, cure/improved/failure
Notes

Randomisation was between azithromycin and, either, dicloxacillin or flucloxacillin; the treatment groups dicloxacillin and flucloxacillin are combined in the results

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was provided.

Allocation concealment (selection bias) Unclear risk

Insufficient information was provided.

Blinding (performance bias and detection bias) High risk

Quote: "An open, randomized..." The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) Low risk

Only 1 participant was missing (in which group was not specified).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline comparison (or compliance data) for the subgroup of impetigo participants.

Randomised? Low risk

Quote: "An open, randomized..."

Quote: "60 were randomized to receive..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Children...were eligible to enter this study."

Quote: "Concurrent treatment with...was not permitted."

Quote: "The principal exclusion criteria were..."

Quote: "Persons were also excluded if..."

Rojas 1985

Methods

Time NR; Dominican Republic; hospital outpatients; only impetigo

Participants
  • Age and M/F ratio NR
  • Bacterial results NR

PE

Interventions
  1. mupirocin ointment 2%, 3 td, 10 to 12 days
  2. placebo/vehicle, 3 td, 10 to 12 days
Outcomes

Outcomes of the trial

  1. 7 to 12 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "The medication was numerically labelled; the protocol ensured double-blind comparisons." Bactroban ointment versus vehicle ointment. It is not clear whether the caregiver and outcome assessor are the same person. There was unclear blinding of the outcome assessor. The participant and the caregiver were probably blinded.

Incomplete outcome data (attrition bias) High risk

Quote: "Fifty patients completed the study." The number of participants that entered into the study was not specified.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline data. There were no compliance data.

Randomised? Low risk

Bactroban ointment versus vehicle ointment - so, probably randomised but not clearly described.

Were both inclusion and exclusion criteria specified? High risk

Quote: "Patients with...entered in the study sequentially." No exclusion criteria was specified.

Ruby 1973

Methods

Summer 1972; Dallas, USA; outpatients; only impetigo

Participants
  • Children, age NR
  • M/F 43/59
  • Only GABHS 33/102, both S. aureus and GABHS 57/102

PNE

Interventions

5 arms:

  1. phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses + HS
  2. phenoxymethyl penicillin 40 to 60,000 units/kg/day in 3 doses
  3. HS + placebo
  4. placebo, 3 td
  5. bacitracin ointment, 2 td
Outcomes

Outcomes of the trial

  1. 5 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk

Quote: "Patients were assigned to one of five treatment groups by a random numbers list."

Quote: "When more than one child from an household was entered in the study, all those children received the same treatment."

Comment: This was probably done.

Allocation concealment (selection bias) High risk

Quote: "Patients were assigned to one of five treatment groups by a random numbers list."

Quote: "When more than one child from an household was entered in the study, all those children received the same treatment." Investigators knew that children in the same household got the same treatment.

Blinding (performance bias and detection bias) High risk

Quote: "Phenoxymethyl penicillin suspension and placebo were coded as 'impecillin' and 'tigocillin'". Also, ointment versus suspension. The bacitracin was not placebo-controlled.

Comment: The outcome assessor, caregiver, and participant were probably not blinded.

Incomplete outcome data (attrition bias) High risk

24/102 participants were omitted in the analysis: 0/20 in group A (penicillin + hexachlorophene), 2/20 in group B (penicillin) (2 not streptococcal positive), 12/23 in group C (placebo) (6 not streptococcal positive, 6 failed to return for first follow-up), 4/17 in group D (placebo+hexachlorophene) (2 not streptococcal positive, 2 failed to return for first follow-up;), 6/22 in group E (bacitracin) (2 not streptococcal positive, 4 failed to return for first follow-up).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. Compliance was good for penicillin (based on urine test) but not reported for other therapy.

Randomised? Low risk

Quote: "Patients were assigned to one of five treatment groups by a random numbers list."

Were both inclusion and exclusion criteria specified? High risk

Quote: "Children with... were excluded."

Quote: "All patients were seen".

Sutton 1992

Methods

Time NR; UK; general practice (n = 20); only impetigo (only facial)

Participants
  • 1 months to 77 years, average 22 years
  • M/F 84/93
  • S. aureus 68/177

PNE

Interventions
  1. fusidic acid cream 3 td, 6 to 8 days
  2. mupirocin ointment 3 td, 6 to 8 days
Outcomes

Outcomes of the trial

  1. 8 days, cure + improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was provided.

Allocation concealment (selection bias) Unclear risk

Insufficient information was provided.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Investigators were not aware of the treatment given until the study was completed."

Quote: "Treatment was allocated randomly in a double-blind manner, medication [was] dispensed in numbered, sealed containers." There was unclear blinding of the caregivers because it is unclear whether this is the same person as the outcome assessor. The participants were blinded.

Incomplete outcome data (attrition bias) High risk

24/201 were omitted in the analysis: 93 were left in the fusidic acid group, 84 were left in the mupirocin group (not further specified). 177/201 were in the analysis. Of the 24 participants who were not analysed for efficacy, 20 returned for follow-up after more than 8 days, 2 defaulted, and 2 violated the study protocol.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. There were no compliance data.

Randomised? Low risk

Quote: "Treatment was allocated randomly in a double-blind manner."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "A total of 201 patients requiring topical antibiotic treatment for facial impetigo were enrolled".

Quote: "Exclusion criteria were..."

Tack 1997

Methods

1992 July to 1993 August; multicentre; US; outpatients; range of skin infections (including impetigo 225/394)

Participants
  • 0 to 13 years (median 5.4)
  • M/F 217/197
  • S. aureus 284/394 (all participants)

PE

Interventions
  1. cefdinir 7 mg/kg/day , 2 td, 10 days
  2. cephalexin 10 mg/kg/day, 4 td, 10 days
Outcomes

Outcomes of the trial

  1. 7 to 14 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was provided.

Allocation concealment (selection bias) Unclear risk

It is unclear whether participants and investigators enrolling participants could foresee assignment.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...a multicenter, randomized, controlled, investigator-blind..." Also, participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor was blinded. The caregiver and participant were not blinded.

Incomplete outcome data (attrition bias) Unclear risk

Quote: "...number of patients excluded for each reason comparable among groups." The proportion of participants not evaluable for reasons of non-compliance was unclear.

Quote: "An intention-to-treat analysis was also performed. This analysis counted as failures all patients who had negative admission cultures or for whom follow-up information was not available."

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance (sex, age, race, infection type). There were no compliance data.

Randomised? Low risk

Quote: "...a multicenter, randomized, controlled, investigator-blind..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Pediatric patients...were eligible for study entry."

Quote: "Patients were prohibited from entering the study if..."

Tack 1998

Methods

January to December 1992; multicentre; USA; outpatients, range of skin infections (including impetigo 62/952)

Participants
  • 13 to 88 years
  • M/F 564/388 (all participants)
  • S. aureus 308/382 (all participants)

PE

Interventions
  1. cefdinir caps 300 mg, 2 td, 10 days
  2. cephalexin caps 500 mg, 4 td, 10 days
Outcomes

Outcomes of the trial

  1. 7 to 16 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was provided.

Allocation concealment (selection bias) Unclear risk

Insufficient information was provided.

Blinding (performance bias and detection bias) Unclear risk

Quote: "This was a double-mask, comparative, multicenter study."

Quote: "Matched placebo capsules were dispensed appropriately to maintain study masking." It is not clear who was blinded (and how). It is unclear whether the outcome assessor and caregiver were blinded. The participants were blinded. 

Incomplete outcome data (attrition bias) High risk

952 randomised participants.

Quote: "Of these, 178 cefdinir patients and 204 cephalexin patients were considered microbiologically assessable and were included in the efficacy analyses." > 20% not included in efficacy analysis because they were not assessed or the study drug was not taken as prescribed (table III). There was no intention-to-treat analysis.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Groups were similar at baseline (table II), though not specified for impetigo participants. There were no compliance data.

Randomised? Low risk

Quote: "Patients were randomized 1:1 to receive..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Eligible patients were..."

Quote: "Exclusion criteria included..."

Tamayo 1991

Methods

Time NR; Mexico; outpatients; only impetigo

Participants
  • 6 months to 12 years, average 4 years 8 months
  • M/F 14/16
  • S. aureus 18/30, S. pyogenes 4/30, both 1/30

PE: not clear

Interventions
  1. rifamycin spray, 2 td, 7 days
  2. mupirocin ointment 2%, 2 td, 7 days
Outcomes

Outcomes of the trial

  1. 1 week, cure/improved
Notes

Both primary (n = 17) and secondary (n = 13) impetigo participants were studied.

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) High risk

Quote: "...open trial". Also, spray versus ointment. The caregiver, outcome assessor, and participant were not blinded.

Incomplete outcome data (attrition bias) Low risk

0/30 participants were omitted in the analysis: 0/15 in the rifamycin group, 0/15 in the mupirocin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance. There were no compliance data.

Randomised? Low risk

Quote: "...fueron asignados al azar." [...were assigned at random.]

Were both inclusion and exclusion criteria specified? Low risk

Quote: "En este estudio únicamente se incluyeron pacientes con lesiones localizades, con área no mayor de 10 cm² Los criterios de exclusión fueron niños con lesiones con un tiempo de evolución mayor de un mes." [In this study, patients were only included if the lesions were smaller than 10 cm². Exclusion criteria were children with lesions present longer than 1 month].

Tassler 1993

Methods

Time NR; multicentre; Europe and South America; hospital-admitted and outpatients; range of skin infections (including impetigo 42/172)

Participants
  • Age 18 to 99 years
  • M/F 159/125 (all part)
  • S. aureus 58% (all participants)

PE

Interventions
  1. fleroxacin 400 mg, 1 td, 7 to 21 days
  2. amoxicillin/clavulanic acid tablets 500/125 mg, 3 td, 7 to 21 days
Outcomes

Outcomes of the trial

  1. 7 days, cure
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available

Blinding (performance bias and detection bias) High risk

Quote: "...open-label". Participants in both groups did not receive the same administrations of study drugs daily. Also, investigators enrolling participants could possibly foresee assignment. The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) High risk

Not only impetigo - it was not specified how many impetigo participants were randomised and included. 27 were analysed in the fleroxacin group, 15 were analysed in the amoxicillin/clavulanic group. Further data was not specified for impetigo participants. Not all participants were assessable for the efficacy analysis, but it was not stated how many.

Selective reporting (reporting bias) Unclear risk

This was not unclear.

Other bias Unclear risk

There was no baseline imbalance. There were no compliance data.

Randomised? Low risk

Quote: "This study was designed as a prospective, randomized, open label..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Inpatients or outpatients of either sex were eligible for inclusion in the study if..."

Quote: "Exclusion criteria were..."

Vainer 1986

Methods

March 1982 to January 1984; Denmark; general practice; only impetigo

Participants
  • Age 1 to 77, average 11 years
  • M/F 71/57
  • No bacterial culture done

PNE

Interventions

3 arms:

  1. fusidic acid cream 2%
  2. tetracycline/polymyxin B ointment
  3. neomycin/bacitracin ointment
Outcomes

Outcomes of the trial

  1. 1 week, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Undersøgelsen var således blindet for lægen, men ikke for patienten." [The study was blinded for the doctor, but not for the patient.] The outcome assessor and caregiver were blinded. Participants were not blinded.

Incomplete outcome data (attrition bias) Low risk

6/134 participants were not included in the analysis: unknown group assignment, reasons were given.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was no baseline imbalance for severity. The used medication is in table 2. There were no compliance data.

Randomised? Low risk

Quote: "...randomiseringsnummer." [...randomisation number.]

Were both inclusion and exclusion criteria specified? Low risk

Quote: "For at indgå i study skulle patienterne have klinisk verificeret impetigo"; "Udelukket var patienter med impetigeniserede eksemer, patienter med..." [Patients were eligible if they had clinical verified impetigo; Excluded were patients with impetiginised eczema and patients with...]

Wachs 1976

Methods

1974; multicentre; USA; outpatients; only impetigo (secondary)

Participants
  • Age/sex NR
  • S. aureus 62/79

PNE

Interventions

3 arms:

  1. betamethasone valerate cream, 3 td
  2. gentamycin cream, 3 td
  3. betamethasone + gentamycin cream, 3 td
Outcomes

Outcomes of the trial

  1. 3 weeks, excellent result
Notes

Secondary impetigo (impetiginised atopic dermatitis)

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available

Blinding (performance bias and detection bias) Low risk

Quote: "...precautions being observed to preserve the blinding of both patients and therapists." Also, participants in both groups received the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were blinded.

Incomplete outcome data (attrition bias) Low risk

4/83 participants were omitted in the analysis (not further specified).

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was a baseline comparison for severity and no imbalance. There were no compliance data.

Randomised? Low risk

Quote: "Patients under the care of an individual investigator were randomly assigned."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "All patients enrolled were clinically judged to have moderate to severe impetiginized..."

Quote: "In order to be accepted for the study..."

Quote: " ...were excluded."

Wainscott 1985

Methods

Time NR; London, UK; outpatients and general practice; range of skin infections (including impetigo 16/39)

Participants
  • Age NR
  • M/F 25/14 (all participants)
  • S. aureus 31/48 (all participants)

PE: not clear

Interventions
  1. mupirocin ointment 2%, 2 td, 7 to 14 days
  2. chlortetracycline cream 3%, 2 td, 7 to 14 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Thirty-nine patients were entered in a randomized, observer-blind trail."

Quote: "...but the medications were packaged identically and not opened in the presence of the physician." The outcome assessor and caregiver were blinded. Participants were not blinded.

Incomplete outcome data (attrition bias) Low risk

3/39 participants were omitted in the analysis: 2/22 in the mupirocin group, 1/17 in the chlortetracycline group. These 3 were excluded from the analysis of results as they received systemic antibiotics for other infections while in the study.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There was a baseline imbalance for age (all infants were in the Bactroban group). This was not specified for impetigo. There were no compliance data.

Randomised? Low risk

Quote: "Thirty-nine patients were entered in a randomized, observer-blind trail."

Were both inclusion and exclusion criteria specified? High risk

Quote: "Patients with lesions suitable for treatment with a topical antibiotic were entered in the study." No exclusion criteria was specified.

Welsh 1987

Methods

Time NR; Monterrey, Mexico; outpatients; range of skin infections (including impetigo 15/60)

Participants
  • Age NR
  • M/F 32/28
  • S. aureus 47/50

PNE

Interventions
  1. mupirocin ointment 2%, 3 td, 5 to 10 days
  2. ampicillin 50 mg, 4 td, 5 to 10 days
Outcomes

Outcomes of the trial

  1. 10 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) High risk

Quote: "...in an open trial." Thereby, the participants in both groups did not receive the same administrations of study drugs daily. The outcome assessor, caregiver, and participant were not blinded.

Incomplete outcome data (attrition bias) Low risk

10/60 participants were omitted in the analysis: 5/32 in the mupirocin group were lost to follow up, 5/28 in the ampicillin group were lost to follow up. These 10 participants were not analysed.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "Patient characteristics were similar in both treatment group in terms of sex, age, and weight." Table I shows no baseline imbalance for severity. There were no compliance data.

Randomised? Low risk

Quote: "A randomized clinical trial..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "...outpatients with primary and secondary skin infections."

Quote: "Patients were excluded from entry into the trial on the basis of..."

White 1989

Methods

1985 to 1987; UK; general practice; range of skin infections (including impetigo 155/390)

Participants
  • Age 11 months to 84 years
  • M/F NR
  • S. aureus 43% (all participants)

PNE

Interventions
  1. mupirocin ointment 2%, 2 td, 7 days
  2. fusidic acid ointment 2%, 3 td, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Low risk

Quote: "...and patients were randomised to receive treatment with either..."

Quote: "For this purpose, a code was designed in blocks of six..."

Quote: "The tubes were supplied in a sealed box labelled with the patient's number. Thereby the observer did not know which antibiotic a patient was receiving."

Comment: This was probably done.

Blinding (performance bias and detection bias) Unclear risk

Quote: "Four plain tubes containing the preparations were supplied for each patient. These were labelled with instructions for use but the name of the antibiotic was omitted. Mupirocin was to be applied twice daily and sodium fusidate thrice daily."

Quote: "The tubes were supplied in a sealed box labelled with the patient's number. Thereby the observer did not know which antibiotic a patient was receiving." The outcome assessor was blinded. The caregiver and participant were probably not blinded because they did not receive the same administrations of study drugs daily.

Incomplete outcome data (attrition bias) High risk

23/413 participants were omitted in the analysis: 12/275 in the mupirocin group (8 failed to attend for assessment, 1 withdrew due to revised diagnosis, 3 were prescribed antibiotics for reasons other than lack of efficacy), 11/138 in the sodium fusidate group (3 failed to attend for assessment, 1 withdrew due to revised diagnosis, 2 were prescribed antibiotics for reasons other than lack of efficacy, 4 due to non-compliance, 1 due to inadequate data). < 20% dropouts, but reasons were not balanced between the groups.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

Quote: "There was a similar distribution of type and severity of infection between the two treatment groups". There were no compliance data.

Randomised? Low risk

Quote: "...observer-blind randomised multi-centre clinical trial."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Any patient with primary or secondary skin infection, other than...was eligible for entry."

Quote: "Patients were excluded if..."

Wilkinson 1988

Methods

Time NR; Quebec, Canada; outpatients; range of skin infections (including impetigo 10/50)

Participants
  • Age/sex NR
  • S. aureus 18/50 (all participants)

PE: not clear

Interventions
  1. mupirocin 2%, 3 td, 7 days
  2. polymyxin B-neomycin (Neosporin), 3 td, 7 days
Outcomes

Outcomes of the trial

  1. 7 days, cure/improved
Notes

-

Risk of bias table
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk

Insufficient information was available.

Allocation concealment (selection bias) Unclear risk

Insufficient information was available.

Blinding (performance bias and detection bias) Unclear risk

Quote: "...double-blind fashion." It was unclear how, and if, the outcome assessor, caregiver, and participant were blinded.

Incomplete outcome data (attrition bias) Low risk

There were 0/10 missing impetigo participants: 0/4 missing in the mupirocin group, 0/6 missing in the neosporin group.

Selective reporting (reporting bias) Unclear risk

This was unclear.

Other bias Unclear risk

There were no baseline characteristics. There were no compliance data.

Randomised? Low risk

Quote: "...were randomly divided into..."

Were both inclusion and exclusion criteria specified? Low risk

Quote: "Fifty patients who appeared at the dermatologic clinic with primary and secondary skin infections of...were randomly divided..."

Quote: "...were excluded from the trial."

Footnotes

all participants = data from all participants in the study, not just the impetigo participants

Abbreviations:
approx = approximately
GABHS = Group A beta Hemolytic Streptococcus
HS = hexachlorophene scrubs
M/F = male/female
NR = not reported
PE = participants excluded from study when culture negative
PNE = participants not excluded
SE = side-effects
susp = suspension
td = times daily
m = months
dd = daily doses
ds = days

Characteristics of excluded studies

Alavena 1987

Reason for exclusion

Randomisation was inadequate.

Anonymous 1998

Reason for exclusion

Results were not separately described for impetigo participants: no randomisation.

Arata 1983

Reason for exclusion

Randomisation was inadequate (serial allocation).

Arata 1994

Reason for exclusion

The results were not separately described for impetigo participants.

Arosemena 1977

Reason for exclusion

The results were not separately described for impetigo participants: only 6/343 participants had impetigo.

Azimi 1999

Reason for exclusion

The results were not separately described for impetigo participants.

Baldwin 1981

Reason for exclusion

The same drug was compared.

Ballantyne 1982

Reason for exclusion

The results were not separately described for impetigo participants: no randomisation.

Bastin 1982

Reason for exclusion

The results were not separately described for impetigo participants.

Bernard 1997

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

Bin Jaafar 1987

Reason for exclusion

No participants had impetigo ( "pyoderma").

Burnett 1963

Reason for exclusion

There was no randomisation.

Cassels-Brown 1981

Reason for exclusion

The design was unacceptable (no RCT).

Colin 1988

Reason for exclusion

The results were not separately described for impetigo participants.

Cordero 1976

Reason for exclusion

There was only 1 impetigo participant.

De Waard 1967

Reason for exclusion

There was no randomisation: 2 arms with the same active drug (though different mode of administration).

Dillon 1970

Reason for exclusion

There was no randomisation.

Dillon 1979a

Reason for exclusion

The results were not separately described for impetigo participants.

Drehobl 1997

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

el Mofty 1990

Reason for exclusion

The results were not separately described for impetigo participants.

Esterly 1970

Reason for exclusion

There was no randomisation.

Faingezicht 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Fedorovskaia 1989

Reason for exclusion

Randomisation was inadequate.

Fleisher 1983

Reason for exclusion

The results were not separately described for impetigo participants.

Forbes 1952

Reason for exclusion

The same drug was compared.

Free 2006

Reason for exclusion

No participants had impetigo (communication: Nicole E. Scangarella).

Gentry 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Gibbs 1987

Reason for exclusion

All impetigo participants received the same treatment.

Golcman 1997

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

Goldfarb 1987

Reason for exclusion

The results were not separately described for impetigo participants.

Gooch 1991

Reason for exclusion

The results were not separately described for impetigo participants.

Hanfling 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Harding 1970

Reason for exclusion

There was 1 drug (flucloxacillin) in 2 doses: the results for impetigo participants were not separately described.

Heskel 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Jacobs 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Jennings 1999

Reason for exclusion

There was only 1 impetigo participant.

Jennings 2003

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

Keeny 1979

Reason for exclusion

The results were not separately described for impetigo participants.

Kotrajaras 1973

Reason for exclusion

The results were not separately described for impetigo participants.

Kumakiri 1988

Reason for exclusion

There was only 1 impetigo participant.

Kumar 1988

Reason for exclusion

No participants had impetigo: 2 forms of the same drug.

Lassus 1990

Reason for exclusion

The results were not separately described for impetigo participants.

Lentino 1984

Reason for exclusion

There was only 1 impetigo participant.

Levenstein 1982

Reason for exclusion

The results were not separately described for impetigo participants.

Lewis-Jones 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Linder 1978

Reason for exclusion

The results were not separately described for impetigo participants.

Linder 1993

Reason for exclusion

The results were not separately described for impetigo participants.

Lipets 1987

Reason for exclusion

No comparison was made.

Liu 1986

Reason for exclusion

No participants had impetigo (impetigo herpetiformis).

MacKenna 1945

Reason for exclusion

Randomisation (serial allocation) was inadequate.

Macotela-Ruiz 1988

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

Mallory 1991

Reason for exclusion

The results were not separately described for impetigo participants.

Manaktala 2009

Reason for exclusion

The results were not separately described for impetigo participants.

McCarty 1992

Reason for exclusion

The results were not separately described for impetigo participants.

McMillan 1969

Reason for exclusion

The results were not separately described for impetigo participants.

Milidiú d Silva 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Nakayama 1983

Reason for exclusion

The results were not separately described for impetigo participants, and it was not an RCT.

Neldner 1991

Reason for exclusion

The results were not separately described for impetigo participants.

Nichols 1997

Reason for exclusion

The results were not separately described for impetigo participants.

Nicolle 1990

Reason for exclusion

The results were not separately described for impetigo participants.

Nolting 1992

Reason for exclusion

No participants had impetigo (pyoderma).

Orecchio 1986

Reason for exclusion

The results were not separately described for impetigo participants.

Pakrooh 1978

Reason for exclusion

No participants had impetigo.

Palazzini 1993

Reason for exclusion

The results were not separately described for impetigo participants.

Parish 1984

Reason for exclusion

The results were not separately described for impetigo participants.

Parish 1991

Reason for exclusion

The results were not separately described for impetigo participants.

Parish 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Parish 1997

Reason for exclusion

The results were not separately described for impetigo participants.

Parish 2000

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no data available).

Parish 2006

Reason for exclusion

No participants had impetigo (communication: Nicole E. Scangarella).

Park 1993

Reason for exclusion

There was no randomisation (personal communication: Seungsoo Sheen).

Pien 1983

Reason for exclusion

The results were not separately described for impetigo participants.

Powers 1991

Reason for exclusion

There were no separate results for clinical cure.

Powers 1993

Reason for exclusion

There were only 2 impetigo participants.

Pusponegoro 1990

Reason for exclusion

There was only 1 impetigo participant,

Risser 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Saenz 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Salzberg 1972

Reason for exclusion

There was only 1 impetigo participant.

Schupbach 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Schwartz 1996

Reason for exclusion

There was only 1 impetigo participant.

Smith 1985

Reason for exclusion

The results were not separately described for impetigo participants.

Smith 1993

Reason for exclusion

There was only 1 impetigo participant.

Sobye 1966

Reason for exclusion

The results were not separately described for impetigo participants.

Stevens 1993

Reason for exclusion

There were 5 participants with "pyoderma".

Tack 1991

Reason for exclusion

The results were not separately described for impetigo participants, and the same drug was compared.

Török 2004

Reason for exclusion

The same drug was compared.

Urbach 1966

Reason for exclusion

No randomisation was described.

Van der Auwera 1985

Reason for exclusion

No participants had impetigo.

Villiger 1986

Reason for exclusion

The results were not separately described for impetigo participants.

Wachs 1992

Reason for exclusion

The results were not separately described for impetigo participants.

Wible 2003

Reason for exclusion

The results were not separately described for impetigo participants (requested, but no reply).

Wolbling 1987

Reason for exclusion

2 doses of 1 drug were compared.

Wong 1989

Reason for exclusion

The results were not separately described for impetigo participants.

Yura 1988

Reason for exclusion

The results were not separately described for impetigo participants.


Characteristics of studies awaiting classification

Chen 2011

Methods

This is an RCT.

Participants
  • Age 6 months to 18 years with uncomplicated skin and soft tissue infections
Interventions

Intervention

  1. clindamycin

Control intervention

  1. cephalexin
Outcomes

Primary outcomes of the trial

  1. Improvement

Secondary outcomes of the trial

  1. Complete resolution
Notes

This is a result of the CSG searches that were run in August 2011.
It is not known how many participants were impetigo patients.

Chosidow 2005

Methods

This is an RCT.

Participants
  • Various skin infections (including impetigo)
Interventions

Intervention

  1. cloxacillin

Control intervention

  1. pristinamycin
Outcomes

Outcomes of the trial

  1. Cure
Notes

This will be included when data on impetigo participants is provided.

Davies 1945

Methods

Please see the 'notes' cell below.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

This is a result of the CSG searches that were run in August 2011.

We were unable to obtain a copy of this trial.

Ghosh 1995

Methods

This is possibly an RCT.

Participants
  • 70 participants of different ages suffering from pyoderma, including infective dermatitis of which 30 participants had impetigo
Interventions

Intervention

  1. neem, haldi, sajina, and garlic oil (Nutriderm oil)

Control intervention

  1. gentian violet
Outcomes

Primary outcomes of the trial

  1. Cure

Secondary outcomes of the trial

  1. Side-effects
Notes

-

Gubelin 1993

Methods

Please see the 'notes' cell below.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

This paper was published in Spanish, and we were unable to obtain a copy.

Kar 1988

Methods

This is possibly an RCT.

Participants
  • 200 children suffering from various types of pyoderma, 94 of which had impetigo
Interventions

Intervention

  1. injection benzathine penicillin

Control intervention

  1. oral sulphamoxole
Outcomes

Outcomes of the trial

  1. Cure after 1 and 2 weeks
Notes

There did not appear to be separate results for impetigo.

Kar 1996

Methods

This is possibly an RCT.

Participants
  • 200 children aged 10 months to 12 years suffering from pyoderma
Interventions

Intervention

  1. 125 mg amoxicilin plus 30 mg clavulanate per 5 ml of suspension, equivalent to 20 mg amoxicillin/kg/day in 3 divided doses

Control interventions

  1. amoxicillin 20 mg/kg/day in 3 divided doses
  2. erythromycin 30 mg/kg/day in 4 divided doses
  3. co-trimoxazole (8 mg trimethoprim + 40 mg sulfamethoxazole/kg/day) in 2 divided dosis
Outcomes

Primary outcomes of the trial

  1. Presence of S. aureus

Secondary outcomes of the trial

  1. Cure
  2. Adverse events
Notes

It was not clear if pyoderma equated to impetigo.

Luby 2002

Methods

This is an RCT.

Participants
  • 162 households in Pakistan
Interventions

Intervention

  1. 1.2% triclocarban-containing soap

Control intervention

  1. an identically appearing placebo
Outcomes

Outcomes of the trial

  1. Impetigo incidence
Notes

This is a result of the CSG searches that were run in August 2011.

Menendez 2007

Methods

This is possibly an RCT.

Participants
  • 136 children (1 day to 14 years) with impetigo
Interventions

Intervention

  1. sunflower oil

Control intervention

  1. mupirocin
Outcomes

Primary outcomes of the trial

  1. Clinical cure after possibly 6 days
Notes

This paper was written in Spanish.

Motohiro 1992

Methods

This is an RCT.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

This is a result of the CSG searches that were run in August 2011.
We were unable to obtain a copy of this trial.

Pierard-Franchimont 2008

Methods

This is an RCT.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

This is a result of the CSG searches that were run in August 2011.

We were unable to obtain a copy of this trial.

Sharquie 2000

Methods

This is possibly an RCT.

Participants
  • 104 participants with impetigo
Interventions

Intervention

  1. tea lotion
  2. tea ointment
  3. soframycin
  4. oral cephalexin
Outcomes

Primary outcomes of the trial

  1. Cure after 7 to 10 days
Notes

-

Suchmacher 2010

Methods

This is an RCT.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

This is a result of the CSG searches that were run in August 2011.

We were unable to obtain a copy of this trial.

Tong 2010

Methods

This is a pilot study.

Participants
  • 13 participants with skin sores
Interventions

Intervention

  1. oral cotrimoxazole
  2. intramuscular benzathine penicillin
Outcomes

Primary outcomes of the trial

  1. Resolution of skin sores
Notes

Australian Trial Register: Is cotrimoxazole safe and efficacious for treatment of skin sores in Aboriginal children: a pilot study

Published in the Journal of Pediatrics and Child Health 2010;46:131-133

Wang 1988

Methods

This is possibly an RCT.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

We were unable to obtain a copy of this trial.

Wang 1995

Methods

This is possibly an RCT.

Participants

Please see the 'notes' cell below.

Interventions

Please see the 'notes' cell below.

Outcomes

Please see the 'notes' cell below.

Notes

We were unable to obtain a copy of this trial.

Characteristics of ongoing studies

ACTRN12609000858291

Study name

An open label randomised controlled trial to determine if 5 days of once-daily oral trimethoprim-sulfamethoxazole or three days of twice-daily oral trimethoprim-sulfamethoxazole will lead to non-inferior cure rates of impetigo compared to a single dose of intramuscular benzathine penicillin G (the current gold standard treatment) in children living in remote Aboriginal communities between the age of 12 weeks to less than 13 years

Methods

See title.

Participants

Inclusion criteria of the trial

  1. Age 12 weeks to less than 13 years at the time written consent is obtained
  2. Diagnosis of purulent or crusted impetigo by criteria outlined in the Booklet "Recognising and Treating Skin Conditions" (East Arnhem Healthy Skin Program (EAHSP), Menzies School of Health Research 2006)
  3. A resident in 1 of the participating (Aboriginal) communities at the time of enrolment and intending to stay in that community for the duration of the study (7 days post-randomisation)
Interventions

Group 1: single dose intramuscular benzathine penicillin G - weight band-based dosing up to 900 mg (> 3 and < 6 kg = 225 mg; > 6 and < 10 kg = 337.5 mg; > 10 and < 15 kg = 450 mg; > 15 and < 20 kg = 675 mg; > 20 kg = 900 mg)

Group 2: trimethoprim-sulfamethoxazole oral suspension 8 + 40 mg/kg (max 320 + 1600 mg) daily for 5 days

Group 3: trimethoprim-sulfamethoxazole oral suspension 4 + 20 mg/kg (max 160 + 800 mg) twice daily for 3 days

Outcomes

Primary outcomes of the trial

  1. The proportion of children successfully treated on day 7 after the commencement of treatment within each of the respective groups. Successfully treated is defined as a child with impetigo which has been clinically classified as sore either healed or improved by a person blinded to the allocated randomisation

Secondary outcomes of the trial

  1. The proportion of children within each of the respective groups who are defined as being successfully treated on day 2 
  2. Prevalence of Staphylococcus aureus (methicillin susceptible and methicillin resistant) and Group A Streptococci per child at day 0, day 2, and day 7 within each treatment group as determined from impetigo swabs collected at the respective time points 
  3. Effect of each treatment on the bacterial resolution of sores at days 2 and 7 as determined by impetigo swabs collected at the respective time points 
  4. Prevalence of nasal carriage of Staphylococcus aureus at baseline and day 7 (including a comparison of the prevalence of methicillin-resistant S. aureus at baseline and day 7)
  5. Evidence of allergy or other reaction to the medication within 7 days of first administration as determined by clinical observation and questioning of caregivers 
Starting date

1st December 2009

Contact information

Ross Andrews (ross.andrews@menzies.edu.au)
Menzies School of Health Research
PO Box 41096 Casuarina, 0811, NT, Australia

Notes

Australian New Zealand Clinical Trial Registry: ACTRN12609000858291

CTRI/2008/091/000060

Study name

An Open Labelled, Double Arm, Randomized, Multicentric, Prospective And Comparative, Phase-III Trial To Evaluate The Safety And Efficacy Of Fixed Dose Combination Of Ceftriaxone And Vancomycin Injection Vs. Vancomycin Injection In Subjects With Various Bacterial Infections

Methods

See above.

Participants

Inclusion criteria of the trial

  • All subjects aged between 18 and 70 years
  • Diagnosed subjects of infectious disease (on clinical evaluation).
  • Subjects willing to give informed consent
  • Subject suffering from any of the following infections - lower respiratory tract infections, skin and skin structure infections, endocarditic, bacterial meningitis and bone infection
Interventions

See above.

Outcomes

Primary outcomes of the trial

  1. Compare the efficacy of a 3.0 g FDC of ceftriaxone and vancomycin injection vs 1.0 g vancomycin injection in subjects with mild to severe bacterial infections

Secondary outcomes of the trial

  1. Evaluate the safety of the test and comparative product
Starting date

8th April 2008

Contact information

kundan.k@nexuscro.com

Notes

It is unclear whether impetigo participants will be included.

NCT00202891

Study name

Sisomicin Cream Vs Nadifloxacin Cream in Primary Pyodermas

Methods

This was to be a randomised, active-control trial.

End point classification - safety/efficacy study

Intervention model - parallel assignment

Masking - open-label

Primary purpose - treatment

Participants

Inclusion criteria of the trial

  • Participants of either sex, suffering from primary pyodermas requiring topical antibiotic therapy without occlusive dressing, > = 6 years of age
  • Written informed consent
Interventions

See title.

Outcomes

None were stated.

Starting date

May 2007

Contact information

Ragunandan Torsekar, MD, FCPS (Principal Investigator)

Rajiv Gandhi Medical College

Notes

The current status of the trial is withdrawn (NCT00202891).

NCT00626795

Study name

Efficacy, Safety, and Tolerability of TD1414 2% Cream in Impetigo and Secondarily Infected Traumatic Lesions (SITL)

Methods

Quote: "This is an international, multicentre, prospective 3-arm parallel-group, phase II proof of concept study comparing the efficacy and safety of 2 dosage regimens (BID 7 days and TID 7 days) of TD1414 2% cream and 1 dosage regimen (BID 7 days) of Bactroban® (mupirocin) 2% cream in adults and children down to 2 years of age with impetigo or SITL. Furthermore, an evaluation of the pharmacokinetics of TD1414 2% cream TID for 7 days will be performed. A total of 664 patients will be enrolled in a stepwise manner according to age groups starting with the oldest age group."

Participants

See above.

Interventions

See above.

Outcomes

Primary outcomes of the trial

  1. Clinical cure at end of treatment according to investigator's assessment

Secondary outcomes of the trial

  1. Clinical cure at follow-up according to investigator's assessment
  2. Clinical cure at end of treatment and follow-up according to investigator's assessment
  3. Bacteriological cure at end of treatment and follow-up
Starting date

February 2008

Contact information

Almena L Free, MD (Principal Investigator)

Anniston Medical Clinic

Anniston, Alabama, United States 36207

Notes

www.clinicaltrials.gov

NCT00852540

Study name

A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Oral Linezolid in the Treatment of Secondarily-Infected Traumatic Lesions and Impetigo Due to Methicillin-Resistant Staphylococcus Aureus

Methods

See above.

Participants

See above.

Interventions

See above.

Outcomes

Primary outcomes of the trial

  1. Number of participants achieving clinical response at follow-up who had methicillin-resistant Staphylococcus aureus (MRSA) as a baseline pathogen

Secondary outcomes of the trial

  1. Number of participants achieving microbiological response at follow-up who had MRSA as a baseline pathogen
  2. Number of participants with clinical response at follow-up
  3. Number of participants who achieved microbiological response at follow-up who had a baseline pathogen
  4. Number of participants with the indicated clinical outcome at the end of therapy who had MRSA as a baseline pathogen
  5. Number of participants with the indicated microbiological outcome at the end of therapy who had MRSA as a baseline pathogen
  6. Number of participants with the indicated clinical outcome at the end of therapy
  7. Number of baseline pathogens with the indicated microbiological outcome at the end of therapy
  8. Number of participants with therapeutic response at follow-up
  9. Mean scores on the skin infection rating scale at visits 1, 2, 3, 4, and 5
  10. Mean wound size at visits 1, 2, 3, 4, and 5
Starting date

April 2009

Contact information

Study Director

GSK Clinical Trials

GlaxoSmithKline

Notes

-

NCT00986856

Study name

A Phase IV Study Comparing Clinical and Bacteriological Efficacy of Fucidin® Cream With Fucidin® Cream Vehicle in the Treatment of Impetigo in Paediatric Patients

Methods

This is a randomised, placebo-controlled trial.

End point classification - safety/efficacy Study

Intervention model: parallel assignment

Masking - double-blind (subject, investigator)

Primary purpose - treatment

Participants

Inclusion criteria of the trial

  • Participants with a clinical diagnosis of impetigo
  • Participants aged 2 to 11 years
  • Participants of either sex
  • Participants whose parent(s) has/have provided written consent
  • Participants with a severity score of 1 for at least 1 of the following signs: pustules/infected bullae, erythema, or infiltration/induration
Interventions
  1. Fucidin® cream versus Fucidin® cream vehicle
Outcomes

Primary outcomes of the trial

  1. The proportion of participants with clinical success (marked improvement or completely cleared) and bacteriological success (eradication) at end of treatment (EOT)

Secondary outcomes of the trial

  1. The proportion of participants with clinical and bacteriological success at visit 2 and 3, and at EOT
  2. The actual change in Total Severity Score from baseline to end of treatment
  3. The distribution of individual sign scores at end of treatment
Starting date

May 2004

Contact information

Inga Odenholt (Principal Investigator)

Malmö University Hospital

Notes

Infomation was obtained from clinicaltrials.gov. Information was requested in August 2010.

NCT01171326

Study name

A Randomized, Parallel-group, Double Blind, Clinical Trial, to Asses the Safety and Efficacy of Topically Applied FXFM244 Antibiotic Foam in the Treatment of Impetigo

Methods

This is a randomised, parallel-group, double (Investigator, participant)-blind, comparative dose range-finding clinical trial.

Participants

Inclusion criteria of the trial

  • Participants with clinical diagnosis of pure impetigo, impetigo contagiosa, or uncomplicated blistering impetigo
  • Participants 2 years of age or older and in general good health
  • Participants with no less than 2 lesions and no more than 7 lesions (area 0.5 x 0.5 cm)
  • No known medical conditions that, in the Investigator's opinion, could interfere with study participation
  • Participant/participant's guardian (in the case of children) willing and able to comply with all requirements of the protocol
  • Participant/participant's guardian willing and able to give written informed consent prior to participation in the study
Interventions

The study will involve 2 treatment groups.

  1. Eligible participants will be randomised to receive either FXFM244 - 1% or FXFM244 - 4% in a blinded fashion. Participants will be treated twice daily for 7 days. Following the screening period and baseline visit, study subjects will return at days 3, 7 and 14. At each visit, participants will be evaluated via lesion count, global assessment tolerability, and safety.
Outcomes

Primary outcomes of the trial

  1. Decrease in lesion count 7 days

Secondary outcomes of the trial

  1. The severity of the overall impetigo condition will be measured at baseline and at all follow-up visits. The severity will be assessed and graded based on the scales for Investigator's Global Assessment and bacteriological testing (days 3, 7, and 14)
Starting date

August 2010

Contact information

Foamix Ltd.

Lev Yasmin Clinic
Natanya, Israel

Notes

This study is probably not eligible for inclusion as 2 dosages of the same drug are used.

[top]

Additional tables

1 Adverse events

Study

Adverse events: nature and number or percentage by treatment group

Arata 1989a; Arata 1989b

mainly gastrointestinal: cefdinir 9/142, cefaclor 4/145

Arredondo 1987

mupirocin: nil reported
dicloxacillin: abdominal pain 1/ 31, vomiting 2/31

Barton 1987

not reported

Barton 1988

abdominal pain: erythromycin 1/ 49, dicloxacillin 1/51
vomiting + rash: dicloxacillin 1/51

Barton 1989

gastrointestinal: erythromycin 8/48, mupirocin 4/49

Bass 1997

not reported

Beitner 1996

diarrhoea: cefadroxil 14/327, flucloxacillin 87/324 (all participants)
severe (stomach ache/rash/fever/vomiting): cefadroxil 14/327, flucloxacillin 2/234 (all participants)

Blaszcyk 1998

mainly gastro-intestinal (half of which were considered treatment-related): clindamycin 150 mg (19%), clindamycin 300 mg (17%), dicloxacillin 10% (all participants)

Britton 1990

minor gastrointestinal: 11 total, equally divided

Bucko 2002a; Bucko 2002b

unclear and not specified for impetigo participants

Christensen 1994

led to withdrawal: skin irritation 1, burning 1, blistering 1 (all fusidic acid - hydrogen peroxide: 0)

mild SE: fusidic acid 9, hydrogen peroxide 13

Ciftci 2002

burning, stinging, itching: 1 in each group

rash: 1 in terbinafine group

Claudy 2001

upper gastrointestinal: fusidic acid 6.8% vs pristinamycin 11.6%

lower gastrointestinal: 2.5% vs 16.7%

hypersensibility: 1.9% vs 5.8%

Dagan 1989

vomiting: amoxicillin 1, amoxicillin and clavulanic acid (augmentin) 0

diarrhoea: amoxicillin 1, amoxicillin and clavulanic acid (augmentin) 0

Dagan 1992

gastrointestinal: erythromycin 11/47, mupirocin 4/51

Daniel 1991a; Daniel 1991b

no subgroup data

Demidovich 1990

nil reported

Dillon 1983

not reported

Dux 1986

pruritus: mupirocin 1/78

nausea and abdominal pain: erythromycin 1/50, cloxacillin 0/20 (all participants)

Eells 1986

not reported

Esterly 1991

mupirocin: nil reported

erythromycin: stomach pain and nausea 1/20, vomiting and irritability 1/20, hysterical attacks 1/20

Farah 1967

not reported

Faye 2007

diarrhoea: amoxicillin 2/64 vs erythromycin 11/65

Fujita 1984

mainly gastrointestinal: enoxacin 11/113, cephalexin 4/110 (all participants)

Gilbert 1989

nil reported

Ginsburg 1978

1 child removed from cefadroxil group because of vomiting; no other SE reported

Giordano 2006

diarrhoea: cefdinir 10% vs cephalexin 4%

nausea: cefdinir 3% vs cephalexin 6%

vaginal mycose of females: cefdinir 3% vs cephalexin 6%

Goldfarb 1988

mild diarrhoea: amupirocin 0/30, erythromycin 5/30

Gonzalez 1989

not reported

Gould 1984

not reported

Gratton 1987

mostly gastrointestinal: erythromycin 8/29

mupirocin: nil reported

Hains 1989

nil reported

Ishii 1977

nil reported

Jaffe 1985

mild diarrhoea: Augmentin® 2/18, cefaclor 5/16 (all participants)

Jaffe 1986

mild staining: hydrocortisone + potassium hydroxyquinoline sulphate cream 2/24, 1% hydrocortisone + 2% miconazole nitrate cream 0/24

Kennedy 1985

nil reported

Kiani 1991

mainly gastrointestinal: azithromycin 30/182, cephalexin: 20/184

Withdrawn: azithromycin 5 (4 gastrointestinal; 1 dizziness and somnolence), cephalexin 1(euphoria) (all participants)

Koning 2003

mainly pain and burning due to povidone iodine: fusidic acid 7/76, placebo 19/80

Koning 2008

any: retapamulin 15/139 vs placebo 2/71

application site pruritis: 9 vs 1

Koranyi 1976

mild abdominal cramps: erythromycin 2/15, bacitracin 0/15

Kuniyuki 2005

not reported

McLinn 1988

gastrointestinal: mupirocin 0/30, erythromycin 6/30

Mertz 1989

nil reported

Montero 1996

mild skin side-effects: azythromycin 3/100, cefaclor 2/100

Moraes Barbosa 1986

not reported

Morley 1988

all local skin reactions: sodium fusidate 2/191, mupirocin 12/163 (all participants)

Nolting 1988

mild burning: sulconazole 0/32, miconazole 1/34

Oranje 2007

local irritation: retapamulin 6/346 vs sodium fusidate 0/173

Pruksachat 1993

not reported

Rice 1992

stomach ache/diarrhoea/vomiting/itching/burning (%): erythromycin 24/10/7/5/0, mupirocin 2/2/0/12/10

Rist 2002

diarrhoea: mupirocin 2/82 vs cephalexin 3/77

Rodriguez-Solares 1993

gastrointestinal: azithromycin 2/25, dicloxacillin/flucloxacillin 2/14

Rojas 1985

nausea/vomiting: mupirocin 0/52, vehicle 1/52

Ruby 1973

not reported

Sutton 1992

local: fusidic acid 2/104, mupirocin 4/97

Tack 1997

mainly gastrointestinal: cefdinir 16%, cephalexin 11% (all participants)

Tack 1998

no subgroup data was available; it included only participants that had pathogens susceptible to both study drugs

Tamayo 1991

nil reported

Tassler 1993

mainly gastrointestinal: fleroxacin 17%, amoxicillin/clavunalate 21% (all participants)

Vainer 1986

total 3%

skin rash: fusidic acid 1/43

burning and itching: tetracycline/polymyxin B ointment and neomycin/bacitracin ointment both 1/44 and 1/41 respectively

Wachs 1976

not reported

Wainscott 1985

nil reported

Welsh 1987

nil reported

White 1989

minor itching or burning: mupirocin 6/263, fusidic acid 2/127 (all participants)

Wilkinson 1988

rash: mupirocin 0/24, neomycin 1/26 (all participants)

Footnotes

None noted.

2 Declared sponsorship or funding

Study

Sponsor (product)

Barton 1987

Fleur de Lis Foundation

Barton 1988

Warner-Lambert Corporation

Barton 1989

Warner- Lambert Corporation

Beitner 1996

Bristol-Myers Squibb (cefadroxil)

Blaszcyk 1998

Pharmacia & Upjohn Asia (clindamycin)

Britton 1990

US Navy Bureau of Medicine and Surgery Clinical Investigation Program

Bucko 2002a, Bucko 2002b

TAF Pharmaceutical Products (cefditoren)

Daniel 1991a; Daniel 1991b

Pfizer Central Research (azithromycin)

Dillon 1983

Eli Lilly Research (cephalexin)

Giordano 2006

Abott Laboratories (cefdinir)

Goldfarb 1988

Beecham Laboratories (mupirocin)

Hains 1989

Bristol-Myers Squibb (cefadroxil)

Jaffe 1985

Beecham Laboratories (amoxicillin+clavulanic acid)

Koning 2003

Dutch College of General Practitioners

Koning 2008

GlaxoSmithKline (retapamulin)

Mertz 1989

Beecham Laboratories (mupirocin)

Oranje 2007

GlaxoSmithKline (retapamulin)

Rist 2002

GlaxoSmithKline (mupirocin)

Sutton 1992

Leo Laboratories (fusidic acid)

Tack 1997

Parke-Davis pharmaceutical research (cefdinir)

Tack 1998

Parke-Davis pharmaceutical research (cefdinir)

Wainscott 1985

Beecham Pharmaceuticals (mupirocin)

White 1989

Beecham Pharmaceuticals (mupirocin)

[top]

References to studies

Included studies

Arata 1989a

Arata J, Kanzaki H, Kanamoto A, Okawara A, Kato N, Kumakiri M. Double-blind comparative study of cefdinir and cefaclor in skin and skin structure infections. Chemotherapy 1989;37:1016-42.

Arata 1989b

Arata J, Yamamoto Y, Tamaki H, Okawara A, Fukaya T, Ishibashi Y. Double-blind study of lomefloxacin versus norfloxacin in the treatment of skin and soft tissue infections. Chemotherapy 1989;37:482-503.

Arredondo 1987

Arredondo JL. Efficacy and tolerance of topical mupirocin compared with oral dicloxacillin in the treatment of primary skin infections. Current Therapeutic Research 1987;41(1):121-7.

Barton 1987

Barton LL, Friedman AD. Impetigo: a reassessment of etiology and therapy. Pediatric Dermatology 1987;4(3):185-8.

Barton 1988

Barton LL, Friedman AD, Portilla MG. Impetigo contagiosa: a comparison of erythromycin and dicloxacillin therapy. Pediatric Dermatology 1988;5(2):88-91.

Barton 1989

Barton LL, Friedman AD, Sharkey AM, Schneller DJ, Swierkosz EM. Impetigo contagiosa III. Comparative efficacy of oral erythromycin and topical mupirocin. Pediatric Dermatology 1989;6(2):134-8.

Bass 1997

Bass JW, Chan DS, Creamer KM, Thompson MW, Malone FJ, Becker TM, et al. Comparison of oral cephalexin, topical mupirocin, and topical bacitracin for treatment of impetigo. Pediatric Infectious Disease Journal 1997;16(7):708-10.

Beitner 1996

Beitner H. Cefadroxil compared with flucloxacillin for skin and soft tissue infection. Journal of Dermatological Treatment 1996;7(3):143-6.

Blaszcyk 1998

Published and unpublished data

Blaszczyk-Kostanecka M, Dobozy A, Dominguez-Soto L, Guerrero R, Hunyadi J, Lopera J, et al. Comparison of two regimens of oral clindamycin versus dicloxacillin in the treatment of mild to moderate skin and soft-tissue infections. Current Therapeutic Research 1998;59(6):341-53.

Britton 1990

Britton JW, Fajardo JE, Krafte-Jacobs B. Comparison of mupirocin and erythromycin in the treatment of impetigo. Journal of Pediatrics 1990;117(5):827-9.

Bucko 2002a

Bucko AD, Hunt BJ, Kidd SL, Hom R. Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections. Clinical Therapeutics 2002;24(7):1134-47.

Bucko 2002b

Bucko AD, Hunt BJ, Kidd SL, Hom R. Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections. Clinical Therapeutics 2002;24(7):1134-47.

Christensen 1994

Christensen OB, Anehus S. Hydrogen peroxide cream: an alternative to topical antibiotics in the treatment of impetigo contagiosa. Acta Dermato-Venerologica 1994;74(6):460-2.

Ciftci 2002

Ciftci E, Guriz H, Aysev AD. Mupirocin vs terbinafine in impetigo. Indian Journal of Pediatrics 2002;69(8):679-82. [MEDLINE: 12356219]

Claudy 2001

Published and unpublished data

Claudy A, Groupe Francais d'Etude. Superficial pyoderma requiring oral antibiotic therapy: fusidic acid versus pristinamycin [Pyodermites superficielles necessitant une antibiotitherapie orale. Acide fusidique versus pristinamycine]. Presse Medicale 2001;30(8):364-8.

Dagan 1989

Dagan R, Bar-David Y. Comparison of amoxicillin and clavulanic acid (augmentin) for the treatment of nonbullous impetigo. American Journal of Diseases of Children 1989;143(8):916-8.

Dagan 1992

Dagan R, Barr-David Y. Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains. Antimicrobial Agents & Chemotherapy 1992;36(2):287-90.

Daniel 1991a

Daniel R. Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. European Azithromycin Study Group. Journal of International Medical Research 1991;19(6):433-45.

Daniel 1991b

Daniel R. Azithromycin, erythromycin and cloxacillin in the treatment of infections of skin and associated soft tissues. European Azithromycin Study Group. Journal of International Medical Research 1991;19(6):433-45.

Demidovich 1990

Demidovich CW, Wittler RR, Ruff ME, Bass JW, Browning WC. Impetigo: current etiology and comparison of penicillin, erythromycin, and cephalexin therapies. American Journal of Diseases of Children 1990;144(12):1313-5.

Dillon 1983

Dillon HC Jr. Treatment of staphylococcal skin infections: a comparison of cephalexin and dicloxacillin. Journal of the American Academy of Dermatology 1983;8(2):177-81.

Dux 1986

Dux PH, Fields L, Pollock D. 2% topical mupirocin versus systemic erythromycin and cloxacillin in primary and secondary skin infections. Current Therapeutic Research 1986;40(5):933-40.

Eells 1986

Eells LD, Mertz PM, Piovanetti Y, Pekoe GM, Eaglstein WH. Topical antibiotic treatment of impetigo with mupirocin. Archives of Dermatology 1986;122(11):1273-6.

Esterly 1991

Esterly NB, Nelson DB, Dunne WM Jr. Impetigo. American Journal of Diseases of Children 1991;145(2):125-6.

Farah 1967

Farah FS, Kurban AK, Malak JA, Shehadeh NH. The treatment of pyoderma with gentamicin. British Journal of Dermatology 1967;79(2):85-8.

Faye 2007

Faye O, Hay RJ, Diawara I, Mahé A. Oral amoxicillin vs. oral erythromycin in the treatment of pyoderma in Bamako, Mali: an open randomized trial. International Journal of Dermatology 2007;46(Suppl 2):19-22.

Fujita 1984

Fujita K, Takahashi H, Hoshino M, Nonami E, Katsumata M, Miura Y. Clinical evaluation of AT-2266 in the treatment of superficial suppurative skin and soft tissue infections. A double blind study in comparison with cephalexin compound granules (L-Keflex). Chemotherapy 1984;32:728-53.

Gilbert 1989

Gilbert M. Topical 2% mupirocin versus 2% fusidic acid ointment in the treatment of primary and secondary skin infections. Journal of the American Academy of Dermatology 1989;20(6):1083-7.

Ginsburg 1978

Ginsburg CM, McCracken GH Jr, Clahsen JC, Thomas ML. Clinical pharmacology of cefadroxil in infants and children. Antimicrobial Agents & Chemotherapy 1978;13(5):845-8.

Giordano 2006

Giordano PA, Elston D, Akinlade BK, Weber K, Notario GF, Busman TA, et al. Cefdinir vs. cephalexin for mild to moderate uncomplicated skin and skin structure infections in adolescents and adults. Current Medical Research & Opinion 2006;22(12):2419-28.

Goldfarb 1988

Goldfarb J, Crenshaw D, O'Horo J, Lemon E, Blumer JL. Randomized clinical trial of topical mupirocin versus oral erythromycin for impetigo. Antimicrobial Agents & Chemotherapy 1988;32(12):1780-3.

Gonzalez 1989

Gonzalez A. Schachner LA, Cleary T, Scott G, Taplin D, Lambert W. Pyoderma in childhood. Advances in Dermatology 1989;4:127-41.

Gould 1984

Gould JC, Smith JH, Moncur H. Mupirocin in general practice: a placebo-controlled trial. Royal Society of Medicine: International Congress and Symposium Series 1984;80:85-93.

Gratton 1987

Gratton D. Topical mupirocin versus oral erythromycin in the treatment of primary and secondary skin infections. International Journal of Dermatology 1987;26(7):472-3.

Hains 1989

Hains CS, Johnson SE, Nelson KG. Once daily cefadroxil therapy for pyoderma. Pediatric Infectious Disease Journal 1989;8(9):648-9.

Ishii 1977

Ishii T et al. Therapetic potential of eksalb simplex against impetigo bullosa [Ekizarube Shimpurekkusu no Suihosei Nokashin ni Taisuru Chiryo Koka]. Kiso to Rinsho (The Clinical Report) 1977;11(2):751-5.

Jaffe 1985

Jaffe AC, O'Brien CA, Reed MD, Blumer, JL. Randomized comparative evaluation of Augmentin® and cefaclor in pediatric skin and soft-tissue infections. Current Therapeutic Research 1985;38(1):160-8.

Jaffe 1986

Jaffe GV, Grimshaw JJ. A clinical trial of hydrocortisone/potassium hydroxyquinoline sulphate ('Quinocort') in the treatment of infected eczema and impetigo in general practice. Pharmatherapeutica 1986;4(10):628-36.

Kennedy 1985

Kennedy CTC, Watts JA, Speller DCE. Bactroban ointment in the treatment of impetigo: a controlled trial against neomycin. In: Proceedings of an International Symposium, Nassau Bahama Islands. 1985:125-129.

Kennedy CTC, Watts JA, Speller DCE. Mupirocin in the treatment of impetigo: a controlled trial against neomycin. In: Mupirocin - a novel topical antibiotic for the treatment of skin infection. Vol. 80. London: Royal Society of Medicine International Congress and Symposium Series, 1984:79-83.

Kiani 1991

Kiani R. Double-blind, double-dummy comparison of azithromycin and cephalexin in the treatment of skin and skin structure infections. European Journal of Clinical Microbiology & Infectious Diseases 1991;10(10):880-4.

Koning 2003

Koning S, van Belkum A, Snijders S, van Leeuwen W, Verbrugh H, Nouwen J, et al. Severity of nonbullous Staphylococcus aureus impetigo in children is associated with strains harboring genetic markers for exfoliative toxin B, Panton-Valentine leukocidin, and the multidrug resistance plasmid pSK41. Journal of Clinical Microbiology 2003;41(7):3017-3021.

* Koning S, van Suijlekom-Smit LWA, Nouwen JL, Verduin CM, Bernsen RMD, Oranje AP, et al. Fusidic acid cream in the treatment of impetigo in general practice: a double blind randomised placebo controlled trial. BMJ 2002;324(7331):203-06.

Koning 2008

Koning S, van der Wouden JC, Chosidow O, Twynholm M, Singh KP, Scangarella N, et al. Efficacy and safety of retapamulin ointment as treatment of impetigo: randomized double-blind multicentre placebo-controlled trial. British Journal of Dermatology 2008;158(5):1077-82.

Koranyi 1976

Koranyi KI, Burech DL, Haynes RE. Evaluation of bacitracin ointment in the treatment of impetigo. Ohio State Medical Journal 1976;72(6):368-70.

Kuniyuki 2005

Kuniyuki S, Nakano K, Maekawa N, Suzuki S. Topical antibiotic treatment of impetigo with tetracycline. Journal of Dermatology 2005;32(10):788-92.

McLinn 1988

McLinn S. A bacteriologically controlled, randomized study comparing the efficacy of 2% mupirocin ointment (Bactroban) with oral erythromycin in the treatment of patients with impetigo. Journal of the American Academy of Dermatology 1990;22(5 Pt 1):883-5.

* McLinn S. Topical mupirocin vs. systemic erythromycin treatment for pyoderma. Pediatric Infectious Disease Journal 1988;7(11):785-90.

Mertz 1989

* Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo J. Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy. Archives of Dermatology 1989;125(8):1069-73.

Mertz, PM. Comparison of the effects of topical mupirocin ointment to orally administered erythromycin in the treatment of impetigo in children. Journal of Investigative Dermatology 1987;88(4):1069-73.

Montero 1996

Montero L. A comparative study of the efficacy, safety and tolerability of azithromycin and cefaclor in the treatment of children with acute skin and/or soft tissue infections. Journal of Antimicrobial Chemotherapy 1996;37(Suppl C):125-31.

Moraes Barbosa 1986

Moraes Barbosa AD. Comparative study between topical 2% sodium fusidate and oral association of chloramphenicol/neomycin/bacitracin in the treatment of staphylococcic impetigo in newborn [Estudo comparativo entre o uso topico de fusidato de sodio a 2%, cloranfenicol, associacao neomicina/bacitracina e eritromicina (oral) no tratamento do impetigo estafilococico do recem-nascido]. Arquivos Brasileiros de Medicina 1986;60(6):509-11.

Morley 1988

Morley PA, Munot LD. A comparison of sodium fusidate ointment and mupirocin ointment in superficial skin sepsis. Current Medical Research Opinion 1988;11(2):142-8.

Nolting 1988

Nolting S, Strauss WB. Treatment of impetigo and ecthyma. A comparison of sulconazole with miconazole. International Journal of Dermatology 1988;27(10):716-9.

Oranje 2007

Oranje AP, Chosidow O, Sacchidanand S, Todd G, Singh K, Scangarella N, et al. Topical retapamulin ointment, 1%, versus sodium fusidate ointment, 2%, for impetigo: a randomized, observer-blinded, noninferiority study. Dermatology 2007;215(4):331-40.

Pruksachat 1993

Pruksachatkunakorn C, Vaniyapongs T, Pruksakorn S. Impetigo: an assessment of etiology and appropriate therapy in infants and children. Journal of the Medical Association of Thailand 1993;76(4):222-9.

Rice 1992

Rice TD, Duggan AK, DeAngelis C. Cost-effectiveness of erythromycin versus mupirocin for the treatment of impetigo in children. Pediatrics 1992;89(2):210-4.

Rist 2002

Rist T, Parish LC, Capin LR, Sulica V, Bushnell WD, Cupo MA. A comparison of the efficacy and safety of mupirocin cream and cephalexin in the treatment of secondarily infected eczema. Clinical & Experimental Dermatology 2002;27(1):14-20.

Rodriguez-Solares 1993

Rodriguez-Solares A, Pérez-Gutiérrez F, Prosperi J, Milgram E, Martin A. A comparative study of the efficacy, safety and tolerance of azithromycin, dicloxacillin and flucloxacillin in the treatment of children with acute skin and skin-structure infections. Journal of Antimicrobial Chemotherapy 1993;31(Suppl E):103-9.

Rojas 1985

* Rojas R, Eells L, Eaglestein W, Provanetti Y, Mertz PM, Mehlisch DR. The efficacy of Bactroban ointment and its vehicle in the treatment of impetigo: a double-blind comparative study. In: Bactroban. Proceedings of an International Symposium; 1984 May 21-22; Nassau, Bahama Islands. 1985:96-102.

Rojas R, Zaias N. The efficacy of Bactroban ointment in the treatment of impetigo as compared to its vehicle: a double-blind comparative study. In: Bactroban. Proceedings of an International Symposium; 1984 May 21-22; Nassau, Bahama Islands. 1985:150-4.

Ruby 1973

Ruby RJ, Nelson JD. The influence of hexachlorophene scrubs on the response to placebo or penicillin therapy in impetigo. Pediatrics 1973;52(6):854-9.

Sutton 1992

Sutton JB. Efficacy and acceptability of fusidic acid cream and mupirocin ointment in facial impetigo. Current Therapeutic Research 1992;51(5):673-8.

Tack 1997

Tack KJ, Keyserling CH, McCarty J, Hedrick JA. Study of use of cefdinir versus cephalexin for treatment of skin infections in pediatric patients. The Cefdinir Pediatric Skin Infection Study Group. Antimicrobial Agents & Chemotherapy 1997;41(4):739-42.

Tack 1998

Tack KJ, Littlejohn TW, Mailloux G, Wolf MM, Keyserling CH. Cefdinir versus cephalexin for the treatment of skin and skin-structure infections. Cefdinir Adult Skin Infection Study Group. Clinical Therapeutics 1998;20(2):244-56.

Tamayo 1991

Tamayo L, Orozco MI, Sosa de Martinez MC. Topical rifamycin and mupirocin in the treatment of impetigo [Rifamycina SV y mupirocín tópicos en el tratamiento del impétigo]. Dermatología Revista Mexicana 1991;55:99-103.

Tassler 1993

Tassler H. Comparative efficacy and safety of oral fleroxacin and amoxicillin/clavunalate potassium in skin and soft-tissue infections. American Journal of Medicine 1993;94(3A):159s-165s.

Vainer 1986

Vainer G, Torbensen E. Treatment of impetigo in general practice. Comparison of 3 locally administered antibiotics [Behandling af impetigo i almen praksis]. Ugeskrift for Laeger 1986;148(20):1202-6.

Wachs 1976

* Wachs GN, Maibach HI. Co-operative double-blind trial of an antibiotic/corticoid combination in impetiginized atopic dermatitis. British Journal of Dermatology 1976;95(3):323-8.

Wainscott 1985

Wainscott G, Huskisson SC. A comparative study of Bactroban ointment and chlortetracycline cream. In: Bactroban. Proceedings of an International Symposium; 1984 May 21-22; Nassau, Bahama Islands. 1985:137-140.

Welsh 1987

Welsh O, Saenz C. Topical mupirocin compared with oral ampicillin in the treatment of primary and secondary skin infections. Current Therapeutic Research 1987;41(1):114-20.

White 1989

White DG, Collins PO, Rowsell RB. Topical antibiotics in the treatment of superficial skin infections in general practice – a comparison of mupirocin with sodium fusidate. Journal of Infection 1989;18(3):221-9.

Wilkinson 1988

Wilkinson RD, Carey WD. Topical mupirocin versus topical neosporin in the treatment of cutaneous infections. International Journal of Dermatology 1988;27(7):514-5.

Excluded studies

Alavena 1987

Alavena R, Roitman J, Cuadros C. Contagious impetigo [Impetigo contagioso. Evulacion de siete esquemas de tratamiento]. Revista de la Sanida de las Fuerzas Policialis 1987;48(1):20-2.

Anonymous 1998

Anonymous. Cefdinir - A new oral Cephalosporin. The Medical Letter 1998;40(1034):85-7.

Arata 1983

Arata J, Nohara N, Suwaki M, Umemura S, Nakagawa S, Miyoshi K, et al. Double-blind comparison of cefadroxil and cephalexin granules in the treatment of impetigo. Japanese Journal of Antibiotics 1983;1443(36):1443-60.

Arata 1994

Arata J, Kanzaki H, Abe Y, Torigoe R, Ohkawara A, Yamanaka K, et al. A multicenter, double-blind, double-placebo comparative study of SY 5555 versus cefaclor in the treatment of skin and skin structure infections. Chemotherapy 1994;42(6):740-60.

Arosemena 1977

* Arosemena R, Bogaert H, Bonilla Dib E, Close de León J, Corrales H, Delgado Mayorga S, et al. Double blind study comparing preparations for topical application [Ensayo doble ciego entre preparaciones combinadas para aplicación tópica]. Investigación Médica Internacional 1977;4:502-8.

Azimi 1999

Azimi PH, Barson WJ, Janner D, Swanson R. Efficacy and safety of ampicillin/subactam and cefuroxime in the treatment of serious skin and skin structure infections in paediatric patients. Unasyn Pediatric Study Group. Pediatric Infectious Disease Journal 1999;18(7):609-13.

Baldwin 1981

Baldwin RJT, Cranfield R. A multi-centre general practice trial comparing fucidin ointment and fucidin cream. British Journal of Clinical Practice 1981;35(4):157-60.

Ballantyne 1982

Ballantyne F. Cefadroxil in the treatment of skin and soft-tissue infections. Journal of Antimicobial Chemotherapy 1982;10 Suppl B:143-7.

Bastin 1982

Bastin R, Rapin M, Kernbaum S. Controlled study of pristinamycin versus oxacillin in staphylococcal infections [Etude clinique de l'activite anti-staphylococcique de la pristinamycine et de l'oxacilline]. Pathologie et Biologie 1982;30(6 part 2):473-5.

Bernard 1997

Published data only (unpublished sought but not used)

Bernard P, Vaillant L, Martin C, Beylot C, Quentin R, Touron D. Pristinamycin versus oxacillin in the treatment of superficial pyoderma [Pristinamycine (Pyostacine 500) versus Oxacilline (Bristopen) dans le traitement des pyodermites superficielles]. Annales de Dermatologie et de Venereologie 1997;124:394-9.

Bin Jaafar 1987

Jaafar RB, Pettit JHS, Gibson JR, Harvey SG, Marks P, Webster A. Trimethoprim-polymyxin B sulfate cream versus fusidic acid cream in the treatment of pyodermas. International Journal of Dermatology 1987;26(1):60-3.

Burnett 1963

Burnett WJ. The route of antibiotic administration in superficial impetigo. New England Journal of Medicine 1963;268:72-5.

Cassels-Brown 1981

Cassels-Brown G. A comparative study of fucidin ointment and cicatrin cream in the treatment of impetigo. British Journal of Clinical Practice 1981;35(4):153-5.

Colin 1988

Colin M, Avon P. Comparative double-blind evaluation of a new topical antibacterial agent, mupirocin, compared with placebo in the treatment of skin and soft tissue infections [Evaluation comparative double aveugle du nouvel agent antibactérien topique, la mupirocine, par rapport à un placebo dans le traitement des infections de la peau et des tussus mous]. Pharmatherapeutica 1988;5(3):198-203.

Cordero 1976

Cordero A. Treatment of skin and soft-tissue infections with cefadroxil, a new oral cephalosporin. Journal of International Medical Research 1976;4(3):176-8.

De Waard 1967

De Waard F, Nelemand FA. The treatment of impetigo with a very long-acting sulpha drug [De behandeling van impetigo met een zeer lang werkend sulfapreparaat]. Huisarts en Wetenschap 1967;10:383-387.

Dillon 1970

Dillon HC. The treatment of streptococcal skin infections. Journal of Pediatrics 1970;76(5):676-84.

Dillon 1979a

Dillon HC, Gray BM, Ware JC. Clinical and laboratory studies with cefaclor: efficacy in skin and soft-tissue infections. Postgraduate Medical Journal 1979;55 Suppl 4:77-81.

Drehobl 1997

Published data only (unpublished sought but not used)

Drehobl M, Koenig L, Barker M, St-Clair P, Maladorno D. Fleroxacin 400 mg once daily versus ofloxacin 400 mg twice daily in skin and soft-tissue infections. Chemotherapy 1997;43(5):378-84.

el Mofty 1990

el Mofty M, Harvey SG, Gibson JR, Calthrop JG, Marks P. Trimethoprim-polymyxin B sulphate cream compared with fusidic acid cream in the treatment of superficial bacterial infection of the skin. Journal of International Medical Research 1990;18(2):89-93.

Esterly 1970

Esterly NB, Markowitz M. The Treatment of Pyoderma in Children. JAMA 1970;212(10):1667-70.

Faingezicht 1992

Faingezicht I, Bolanos HJ, Arias G, Guevara J, Ruiz M. Comparative study of cefprozil and cefaclor in children with bacterial infections of skin and skin structures. Pediatric Infectious Diseases Journal 1992;11(11):976-8.

Fedorovskaia 1989

Federovskaia RF, Bukharovich AM, Danilova TN, Masyukova SA, Blinova MY. Tomicide paste in combined therapy of pyoderma [Opyt primeneniia tomitsidovoi pasty v kompleksnoi terapii bol'nykh piodermiiami]. Vestnik Dermatologii i Venerologii 1989;9:63-6.

Fleisher 1983

Fleisher GR, Wilmott CM, Campos JM. Amoxicillin combined with clavulanic acid for the treatment of soft-tissue infections in children. Antimicrobial Agents & Chemotherapy 1983;24(5):679-81.

Forbes 1952

Forbes MA. A clinical evaluation of neomycin in different bases. Southern Medical Journal 1952;45(3):235-9.

Free 2006

Free A, Roth E, Dalessandro M, Hiram J, Scangarella N, Shawar R, et al. Retapamulin ointment twice daily for 5 days vs oral cephalexin twice daily for 10 days for empiric treatment of secondarily infected traumatic lesions of the skin. Skinmed 2006;5(5):224-32.

Gentry 1985

Gentry LO. Treatment of skin, skin structure, bone, and joint infections with ceftazidime. American Journal of Medicine 1985;79(Suppl 2a):67-74.

Gibbs 1987

Gibbs DL, Kashin P, Jevons S. Comparative and non-comparative studies of the efficacy and tolerance of tioconazole cream 1% versus another imidazole and/or placebo in neonates and infants with candidal diaper rash and/or impetigo. Journal of International Medical Research 1987;15(1):23-31.

Golcman 1997

Published data only (unpublished sought but not used)

Golcman B, Tuma SR, Golcman R, Schalka S, Gonzalez MA. Efficacy and safety of cefprozil and cefaclor on cutaneous infections. Anais Brasileiros de Dermatologia 1997;72(1):79-82.

Goldfarb 1987

Goldfarb J, Aronoff SC, Jaffe A, Reed MD,Blumer JL. Sultamicillin in the treatment of superficial skin and soft tissue infections in children. Antimicrobial Agents & Chemotherapy 1987;31(4):663-4.

Gooch 1991

Gooch WM, Kaminester L, Cole GW, Binder R, Morman MR, Swinehart JM, et al. Clinical comparison of cefuroxime axetil, cephalexin and cefadroxil in the treatment of patients with primary infections of the skin or skin structures. Dermatologica 1991;183(1):336-43.

Hanfling 1992

Hanfling MJ, Hausinger SA, Squires J. Loracarbef versus cefaclor in pediatric skin and skin structure infections. Pediatric Infectious Disease Journal 1992;11 Suppl 8:27-30.

Harding 1970

Harding JW, Path MRC. General practitioners' forum. Flucloxacillin in the treatment of skin and soft-tissue infections. Practioner 1970;205(230):801-6.

Heskel 1992

Heskel NS, Siepman NC, Pichotta PJ, Green E M, Stoll RW. Erythromycin versus cefadroxil in the treatment of skin infections. International Journal of Dermatology 1992;31(2):131-3.

Jacobs 1992

Jacobs RF, Brown WD, Chartrand S, Darden P, Drehobl MA, Yetman R, et al. Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections. Antimicrobial Agents & Chemotherapy 1992;36(8):1614-8.

Jennings 1999

Jennings MB, Alfieri D, Kosinski M, Weinberg JM. An investigator-blind study of the efficacy and safety of azithromycin versus cefadroxil in the treatment of skin and skin structure infections of the foot. The Foot: International Journal of Clinical Foot Science 1999;9(2):68-72.

Jennings 2003

Jennings MB, McCarty JM, Scheffler NM, Puopolo AD, Rothermel CD. Comparison of azithromycin and cefadroxil for the treatment of uncomplicated skin and skin structure infections. Cutis 2003;72(3):240-4.

Keeny 1979

Keeney RE, Seamans ML, Russo RM, Gururaj VJ, Alle JE. The comparative efficacy of minocycline and penicillin-V in Staphylococcus aureus skin and soft-tissue infections. Cutis 1979;23(5):711-8.

Kotrajaras 1973

Kotrajaras, R. Studies of bacterial infections of skin in Bangkok. International Journal of Dermatology 1973;12(3):163-5.

Kumakiri 1988

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Macotela-Ruiz 1988

Published data only (unpublished sought but not used)

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Parish 1991

Parish LC, Jungkind DL. Systemic antimicrobial therapy in skin and skin structure infections: comparison of temafloxacin and ciprofloxacin. American Journal of Medicine 1991;91 Suppl 6A:115-9.

Parish 1992

Parish LC, Doyle CA, Durham SJ, Wilber RB. Cefprozil versus cefaclor in the treatment of mild to moderate skin and skin-structure infections. Clinical Therapeutics 1992;14(3):458-69.

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Studies awaiting classification

Chen 2011

Chen AE, Carroll KC, Diener-West M, Ross T, Ordun J, Goldstein MA, et al. Randomized controlled trial of cephalexin versus clindamycin for uncomplicated pediatric skin infections. Pediatrics 2011;127(3):e573-80.

Chosidow 2005

Chosidow O, Bernard P, Berbis P, Humbert P, Crickx B, Jarlier V, et al. Cloxacillin versus pristinamycin for superficial pyodermas: A randomized, open-label, non-inferiority study. Dermatology 2005;210(4):370-4.

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Ghosh SK. A study on the role of neem, haldi, sajina and garlic oil (Nutriderm Oil) in pyoderma and infective dermatitis. Indian Journal of Dermatology 1995;40(2):73-5.

Gubelin 1993

Gübelin HW, Zegpi E, Oroz MJ, Del Canto ETM, Pérez J, Grandi P et al. Comparative clinique study of topical mupirocine and oral cloxacillin in the treatment of skin infections [Estudio clínico comparativo de mupirocine tópico y cloxacilina oral en el tratamiento de infecciones cutáneas]. Dermatología (Santiago de Chile) 1993;9(2):78-83.

Kar 1988

Kar PK. A study of treatment of pyoderma with injection benzathine penicillin. Journal of the Indian Medical Association 1988;86(1):8-11.

Kar 1996

Kar PK. A combination of amoxicillin and clavulanic acid in the treatment of pyoderma in children. Indian Journal of Dermatology Venereology & Leprology 1996;62(2):91-4.

Luby 2002

Luby S, Agboatwalla M, Schnell BM, Hoekstra RM, Rahbar MH, Keswick BH. The effect of antibacterial soap on impetigo incidence, Karachi, Pakistan. American Journal of Tropical Medicine & Hygiene 2002;67(4):430-5.

Menendez 2007

Menéndez S, Fernández M, Amoroto M, Uranga R, Acuña P, Elisa Benítez J, et al. Efficacy and security of topical OLEOZON in the treatment of patients with impetigo [Eficacia y seguridad del OLEOZON tópico en el tratamiento de pacientes con impétigo]. Revista Panamericana de Infectología 2007;9(2):23-9.

Motohiro 1992

Motohiro T, Aramaki M, Oda, K, Kawakami A, Koga T, Tomita S, et al. Clinical studies on cefprozil granules in pediatric skin soft tissues infections [[unknown]]. Japanese Journal of Antibiotics 1992;45(12):1684-99.

Pierard-Franchimont 2008

Pierard-Franchimont CHF, Szepetiuk G, Devillers C, Pierard GE. Comparative randomized intraindividual assessment of the efficacy of fusidic acid and povidone iodine in impetigo. Current Topics in Pharmacology 2008;12(2):113-7.

Sharquie 2000

Sharquie KE, al-Turfi IA, al-Salloum SM. The antibacterial activity of tea in vitro and in vivo (in patients with impetigo contagiosa). Journal of Dermatology 2000;27(11):706-10.

Suchmacher 2010

Suchmacher Neto M, Geller M, Ribeiro MG, Guimarães OR, Oliveira L, Cunha KSG, et al. Clinical assessment of azithromycin dihydrate in the treatment of pediatric impetigo [Avaliação clínica de azitromicina di-hidratada no tratamento de impetigo pediátrico]. Pediatr Mod 2010 2010;46(5):unknown.

Tong 2010

Tong SYC, Andrews RM, Kearns T, Gundjirryirr R, McDonald MI, Currie BJ, et al. Trimethoprim-sulfamethoxazole compared with benzathine penicillin for treatment of impetigo in Aboriginal children: A pilot randomised controlled trial. Journal of Paedatrics & Child Health 2010;46(3):131-3. [Other: ACTRN12607000592448]

Wang 1988

Wang YM. Treating impetigo by traditional chinese medicine decoction lotion [In Chinese]. Journal of Integrated Traditional and Western Medicine [Zhong Xi Yi Jie He Za Zhi] 1988;8(7):442.

Wang 1995

Wang ZB. Shen Qi Tang in treating impetigo in palm and toe in 168 cases [In Chinese]. Shandong Journal of Traditional Chinese Medicine [Shan Dong Zhong Yi Za Zhi] 1995;14(11):500-501.

Ongoing studies

ACTRN12609000858291

ACTRN12609000858291. An open label randomised controlled trial to determine if 5 days of once-daily oral trimethoprim-sulfamethoxazole or three days of twice-daily oral trimethoprim-sulfamethoxazole will lead to non-inferior cure rates of impetigo compared to a single dose of intramuscular benzathine penicillin G (the current gold standard treatment) in children living in remote Aboriginal communities between the age of 12 weeks to less than 13 years. www.anzctr.org.au/trial_view.aspx?id=83543 (accessed 3 August 2010).

CTRI/2008/091/000060

CTRI/2008/091/000060. A clinical trial to study the safety and efficacy of combination drug, vancomycin and ceftriaxone compared to vancomycin in mild to severe bacterial infections. apps.who.int/trialsearch/trial.aspx?TrialID=CTRI/2008/091/000060 (accessed 3 August 2010).

NCT00202891

NCT00202891. Sisomicin Cream Vs Nadifloxacin Cream in Primary Pyodermas (Study P04460)(TERMINATED). clinicaltrials.gov/ct2/results?term=NCT00202891 (accessed 3 August 2010).

NCT00626795

NCT00626795. Efficacy, Safety, and Tolerability of TD1414 2% Cream in Impetigo and Secondarily Infected Traumatic Lesions (SITL). clinicaltrials.gov/ct2/show/NCT00626795?term=NCT00626795 (accessed 3 August 2010).

NCT00852540

Unpublished data only [Other: ]

110978. A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, versus Oral Linezolid in the Treatment of Secondarily-Infected Traumatic Lesions and Impetigo Due to Methicillin-Resistant Staphylococcus aureus. www.gsk-clinicalstudyregister.com/protocol_detail.jsp?protocolId=110978&studyId=4EDB3886-9DE1-4A2F-8245-226DEC1B7BEF&compound=retapamulin&type=Compound&letterrange=Q-U (accessed 3 August 2010).

NCT00986856

NCT00986856. Fucidin® Cream in the Treatment of Impetigo. clinicaltrials.gov/ct2/results?term=NCT00986856 (accessed 3 August 2010).

NCT01171326

Unpublished data only

NCT01171326. Study to evaluate the safety and efficacy of topical minocycline FXFM244 in impetigo patients. clinicaltrials.gov/ct2/results?term=NCT01171326 (accessed 11 July 2011).

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Other references

Additional references

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Other published versions of this review

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Koning S, Verhagen AP, van Suijlekom-Smit LWA, Morris AD, Butler C, van der Wouden JC. Interventions for impetigo. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD003261. DOI: 10.1002/14651858.CD003261.

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Data and analyses

1 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs placebo (P)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
1.1 Cure/improvement 6 575 Risk Ratio (M-H, Random, 95% CI) 2.24 [1.61, 3.13]
  1.1.1 Mupirocin 3 173 Risk Ratio (M-H, Random, 95% CI) 2.18 [1.58, 3.00]
  1.1.2 Fusidic acid 1 156 Risk Ratio (M-H, Random, 95% CI) 4.42 [2.39, 8.17]
  1.1.3 Bacitracin 1 36 Risk Ratio (M-H, Random, 95% CI) 3.71 [0.16, 85.29]
  1.1.4 Retapamulin 1 210 Risk Ratio (M-H, Random, 95% CI) 1.64 [1.30, 2.07]
 

2 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs another topical (Top) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
2.1 Cure/improvement 14 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
  2.1.1 Mupirocin vs rifamycin 1 17 Risk Ratio (M-H, Fixed, 95% CI) 1.72 [0.96, 3.07]
  2.1.2 Mupirocin vs neomycin 1 32 Risk Ratio (M-H, Fixed, 95% CI) 1.29 [0.98, 1.71]
  2.1.3 Mupirocin vs bacitracin 1 16 Risk Ratio (M-H, Fixed, 95% CI) 2.57 [0.97, 6.80]
  2.1.4 Mupirocin vs chlortetracycline 1 14 Risk Ratio (M-H, Fixed, 95% CI) 1.11 [0.78, 1.59]
  2.1.5 Mupirocin vs polymyxin B/neomycin 1 8 Risk Ratio (M-H, Fixed, 95% CI) 1.06 [0.56, 2.01]
  2.1.6 Fusidic acid vs neomycin/bacitracin 1 84 Risk Ratio (M-H, Fixed, 95% CI) 0.92 [0.66, 1.27]
  2.1.7 Fusidic acid vs tetracycline/polymyxin B 1 87 Risk Ratio (M-H, Fixed, 95% CI) 1.06 [0.75, 1.52]
  2.1.8 Retapamulin vs fusidic acid 1 517 Risk Ratio (M-H, Fixed, 95% CI) 1.05 [1.00, 1.11]
  2.1.9 Sulcanozol vs miconazole 1 66 Risk Ratio (M-H, Fixed, 95% CI) 5.31 [0.66, 43.04]
  2.1.10 Hydrocortisone + hydroxyquinoline vs hydrocortisone + miconazole 1 43 Risk Ratio (M-H, Fixed, 95% CI) 2.06 [0.89, 4.76]
  2.1.11 Gentamycin vs neomycin 1 128 Risk Ratio (M-H, Fixed, 95% CI) 1.43 [1.03, 1.98]
  2.1.12 Mupirocin vs fusidic acid 4 440 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.95, 1.11]
 

3 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
3.1 Cure/improvement 15 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
  3.1.1 Mupirocin vs erythromycin 10 581 Risk Ratio (M-H, Fixed, 95% CI) 1.07 [1.01, 1.13]
  3.1.2 Mupirocin vs dicloxacillin 1 53 Risk Ratio (M-H, Fixed, 95% CI) 1.04 [0.94, 1.15]
  3.1.3 Mupirocin vs cephalexin 1 17 Risk Ratio (M-H, Fixed, 95% CI) 0.95 [0.66, 1.37]
  3.1.4 Mupirocin vs ampicillin 1 13 Risk Ratio (M-H, Fixed, 95% CI) 1.78 [0.65, 4.87]
  3.1.5 Bacitracin vs erythromycin 1 30 Risk Ratio (M-H, Fixed, 95% CI) 0.50 [0.22, 1.11]
  3.1.6 Bacitracin vs penicillin 1 34 Risk Ratio (M-H, Fixed, 95% CI) 0.38 [0.04, 3.25]
  3.1.7 Bacitracin vs cephalexin 1 19 Risk Ratio (M-H, Fixed, 95% CI) 0.37 [0.14, 0.95]
3.2 Cure/improvement 2 137 Risk Ratio (M-H, Random, 95% CI) 1.12 [0.86, 1.46]
  3.2.1 Mupirocin vs erythromycin: observer blinded studies 2 137 Risk Ratio (M-H, Random, 95% CI) 1.12 [0.86, 1.46]
 

4 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs disinfecting treatments (Dt)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
4.1 Cure/improvement 2 292 Risk Ratio (M-H, Fixed, 95% CI) 1.15 [1.01, 1.32]
  4.1.1 Bacitracin vs hexachlorophene 1 36 Risk Ratio (M-H, Fixed, 95% CI) 3.71 [0.16, 85.29]
  4.1.2 Fusidic acid vs hydrogen peroxide 1 256 Risk Ratio (M-H, Fixed, 95% CI) 1.14 [1.00, 1.31]
 

5 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs antifungal (Af)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
5.1 Cure 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  5.1.1 Mupirocin vs terbinafine 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

6 Non-bullous impetigo: topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab) vs topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
6.1 Cure 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  6.1.1 Tetracyclin + cefdinir vs tetracyclin + minomycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  6.1.2 Tetracyclin + cefdinir vs tetracyclin + fosfomycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  6.1.3 Tetracyclin + minomycin vs tetracyclin + fosfomycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

7 Non-bullous impetigo: topical (Top) antibiotic (Ab) vs topical (Top) antibiotic (Ab) + oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
7.1 Cure 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
  7.1.1 Tetracyclin vs tetracyclin + cefdinir 1 34 Risk Ratio (M-H, Fixed, 95% CI) 1.57 [0.69, 3.58]
  7.1.2 Tetracyclin vs tetracyclin + minomycin 1 33 Risk Ratio (M-H, Fixed, 95% CI) 0.85 [0.62, 1.15]
  7.1.3 Tetracyclin vs tetracyclin + fosfomycin 1 38 Risk Ratio (M-H, Fixed, 95% CI) 1.31 [0.76, 2.25]
 

8 Non-bullous impetigo: oral (Or) antibiotics (Ab) vs placebo (P)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
8.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  8.1.1 Penicillin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

9 Non-bullous impetigo: oral (Or) antibiotic (Ab) (cephalosporin) vs another oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
9.1 Cure/improvement 6 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.1 Cephalexin vs penicillin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.2 Cephalexin vs erythromycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.3 Cephalexin vs azithromycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.4 Cefaclor vs azithromycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.5 Cefaclor vs amoxicillin/clavulanic acid 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.6 Cefadroxil vs penicillin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  9.1.7 Cefadroxil vs flucloxacillin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

10 Non-bullous impetigo: oral (Or) cephalosporin vs other oral (Or) cephalosporin

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
10.1 Cure/improvement 7 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
  10.1.1 Cephalexin vs cefadroxil 1 96 Risk Ratio (M-H, Fixed, 95% CI) 0.99 [0.88, 1.12]
  10.1.2 Cephalexin vs cefdinir 3 201 Risk Ratio (M-H, Fixed, 95% CI) 0.95 [0.88, 1.03]
  10.1.3 Cefaclor vs cefdinir 1 13 Risk Ratio (M-H, Fixed, 95% CI) 0.64 [0.23, 1.82]
  10.1.4 Cefditoren vs cefuroxime 1 58 Risk Ratio (M-H, Fixed, 95% CI) 0.73 [0.55, 0.97]
  10.1.5 Cefditoren vs cefadroxil 1 74 Risk Ratio (M-H, Fixed, 95% CI) 1.02 [0.78, 1.33]
 

11 Non-bullous impetigo: oral (Or) macrolide vs penicillin

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
11.1 Cure/improvement 7 363 Risk Ratio (M-H, Fixed, 95% CI) 1.06 [0.98, 1.15]
  11.1.1 Erythromycin vs penicillin V 2 79 Risk Ratio (M-H, Fixed, 95% CI) 1.29 [1.07, 1.56]
  11.1.2 Erythromycin vs dicloxacillin 1 58 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.94, 1.13]
  11.1.3 Erythromycin vs amoxicillin 1 129 Risk Ratio (M-H, Fixed, 95% CI) 1.00 [0.89, 1.13]
  11.1.4 Azithromycin vs cloxacillin 1 16 Risk Ratio (M-H, Fixed, 95% CI) 1.40 [0.57, 3.43]
  11.1.5 Azithromycin vs flucloxacillin/dicloxacillin 1 39 Risk Ratio (M-H, Fixed, 95% CI) 0.84 [0.61, 1.16]
  11.1.6 Clindamycin vs dicloxacillin 1 42 Risk Ratio (M-H, Fixed, 95% CI) 1.01 [0.80, 1.27]
 

12 Non-bullous impetigo: oral (Or) macrolide vs another oral (Or) macrolide

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
12.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  12.1.1 Azithromycin vs erythromycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

13 Non-bullous impetigo: oral (Or) penicillin vs other oral (Or) antibiotic (Ab) (including penicillin)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
13.1 Cure/improvement 4 Risk Ratio (M-H, Random, 95% CI) Subtotals only
  13.1.1 Amoxicillin + clavulanic acid vs amoxicillin 1 44 Risk Ratio (M-H, Random, 95% CI) 1.40 [1.04, 1.89]
  13.1.2 Amoxicillin + clavulanic acid vs fleroxacin 1 42 Risk Ratio (M-H, Random, 95% CI) 1.14 [0.80, 1.62]
  13.1.3 Cloxacillin vs penicillin 2 166 Risk Ratio (M-H, Random, 95% CI) 1.59 [1.21, 2.08]
 

14 Non-bullous impetigo: other comparisons of oral (Or) antibiotics (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
14.1 Cure/improvement 2 Risk Ratio (M-H, Fixed, 95% CI) No totals
  14.1.1 Lomefloxacin vs norfloxacin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  14.1.2 Fusidic acid vs pristinamycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

15 Non-bullous impetigo: oral (Or) antibiotics (Ab) vs disinfecting treatments (Dt)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
15.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  15.1.1 Penicillin vs hexachlorophene 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

16 Bullous impetigo: topical (Top) antimicrobial vs placebo (P)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
16.1 Cured/improved after 3 to 4 days 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  16.1.1 Eksalb vs placebo 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

17 Bullous impetigo: topical (Top) antibiotic (Ab) vs another topical (Top) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
17.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  17.1.1 Fusidic acid vs neomycin/bacitracin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  17.1.2 Fusidic acid vs chloramphenicol 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  17.1.3 Chloramphenicol vs neomycin/bacitracin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

18 Bullous impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
18.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) Subtotals only
  18.1.1 Fusidic acid vs erythromycin 1 24 Risk Ratio (M-H, Fixed, 95% CI) 1.43 [0.83, 2.45]
  18.1.2 Neomycin/bacitracin vs erythromycin 1 24 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.02, 0.99]
  18.1.3 Chloramphenicol vs erythromycin 1 24 Risk Ratio (M-H, Fixed, 95% CI) 0.29 [0.07, 1.10]
 

19 Bullous impetigo: oral (Or) antibiotic (Ab) vs another oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
19.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  19.1.1 Cephalexin vs dicloxacillin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

20 Secondary impetigo: topical (Top) antibiotic (Ab) vs oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
20.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  20.1.1 Mupirocin calcium vs cephalexin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

21 Secondary impetigo: steroid (S) vs antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
21.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  21.1.1 Betamethasone vs gentamycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

22 Secondary impetigo: steroid (S) + antibiotic (Ab) vs steroid (S)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
22.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  22.1.1 Betamethasone + gentamycin vs betamethasone 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

23 Secondary impetigo: steroid (S) + antibiotic (Ab) vs antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
23.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  23.1.1 Betamethasone + gentamycin vs gentamycin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

24 Secondary impetigo: oral (Or) antibiotic (Ab) vs another oral (Or) antibiotic (Ab)

Outcome or Subgroup Studies Participants Statistical Method Effect Estimate
24.1 Cure/improvement 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
  24.1.1 Cephalexin vs enoxacin 1 Risk Ratio (M-H, Fixed, 95% CI) No totals
 

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Figures

Figure 1

Refer to figure 1 caption below.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study (Figure 1).

Figure 2

Refer to figure 2 caption below.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies (Figure 2).

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Sources of support

Internal sources

  • Department of General Practice, Erasmus MC - University Medical Center Rotterdam, Netherlands

External sources

  • No sources of support provided

[top]

Feedback

[top]

Appendices

1 CENTRAL search strategy

#1(impetig* or pyoderma ):ti
#2MeSH descriptor Impetigo explode all trees in MeSH products
#3(#1 OR #2)
#4SR-SKIN in All Fields in all products
#5(#3 AND NOT #4)

2 MEDLINE (OVID) search strategy

1. randomized controlled trial.pt.
2. controlled clinical trial.pt.
3. randomized.ab.
4. placebo.ab.
5. clinical trials as topic.sh.
6. randomly.ab.
7. trial.ti.
8. 1 or 2 or 3 or 4 or 5 or 6 or 7
9. (animals not (human and animals)).sh.
10. 8 not 9
11. exp Staphylococcal Infections/ or stapylococcal skin infections.mp.
12. impetigo.mp. or exp Impetigo/
13. exp Pyoderma/ or pyoderma.mp.
14. 11 or 13 or 12
15. 10 and 14

3 EMBASE (OVID) search strategy

1. random$.mp.
2. factorial$.mp.
3. (crossover$ or cross-over$).mp.
4. placebo$.mp. or PLACEBO/
5. (doubl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
6. (singl$ adj blind$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
7. (assign$ or allocat$).mp.
8. volunteer$.mp. or VOLUNTEER/
9. Crossover Procedure/
10. Double Blind Procedure/
11. Randomized Controlled Trial/
12. Single Blind Procedure/
13. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12
14. impetigo.mp. or exp IMPETIGO/
15. exp PYODERMA/ or pyoderma.mp.
16. exp Staphylococcus Aureus/ or stapylococcus aureus.mp.
17. 16 or 15 or 14
18. 13 and 17

4 LILACS search strategy

((Pt RANDOMIZED CONTROLLED TRIAL OR Pt CONTROLLED CLINICAL TRIAL OR Mh RANDOMIZED CONTROLLED TRIALS OR Mh RANDOM ALLOCATION OR Mh DOUBLE-BLIND METHOD OR Mh SINGLE-BLIND METHOD OR Pt MULTICENTER STUDY) OR ((tw ensaio or tw ensayo or tw trial) and (tw azar or tw acaso or tw placebo or tw control$ or tw aleat$ or tw random$ or (tw duplo and tw cego) or (tw doble and tw ciego) or (tw double and tw blind)) and tw clinic$)) AND NOT ((CT ANIMALS OR MH ANIMALS OR CT RABBITS OR CT MICE OR MH RATS OR MH PRIMATES OR MH DOGS OR MH RABBITS OR MH SWINE) AND NOT (CT HUMAN AND CT ANIMALS)) [Palavras] and (impetigo or pyoderma or piodermia or piodermitis or (staphyloccus aureus) or estafilococo) [Palavras]


This review is published as a Cochrane review in The Cochrane Library, Issue 6, 2015 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as new evidence emerges and in response to feedback. The Cochrane Library should be consulted for the most recent recent version of the review.