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Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units

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Authors

Mohan Pammi1, Oya Eddama2, Leonard E Weisman3

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


1Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA [top]
2National Perinatal Epidemiology Unit, NPEU, Institute of Health Sciences, Oxford, UK [top]
3Dept of Pediatrics, Section of Neonatology, Baylor College of Medicine, Houston, Texas, USA [top]

Citation example: Pammi M, Eddama O, Weisman LE. Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD006068. DOI: 10.1002/14651858.CD006068.pub3.

Contact person

Mohan Pammi

Section of Neonatology, Department of Pediatrics
Baylor College of Medicine
6621, Fannin, MC.WT 6-104
Houston Texas 77030
USA

E-mail: mohanv@bcm.tmc.edu
E-mail 2: suseela12@hotmail.com

Dates

Assessed as Up-to-date: 08 July 2011
Date of Search: 07 July 2011
Next Stage Expected: 09 July 2013
Protocol First Published: Issue 3, 2006
Review First Published: Issue 3, 2007
Last Citation Issue: Issue 11, 2011

What's new

Date / Event Description
08 July 2011
Updated

This updates the review 'Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units' published in the Cochrane Database of Systematic Reviews (Pammi 2007).

08 July 2011
New citation: conclusions not changed

Updated search in July 2011did not identify any new trials for inclusion.

No changes to conclusions.

History

Date / Event Description
07 December 2010
Amended

Contact details updated.

22 August 2008
Amended

Converted to new review format.

Abstract

Background

Candida is a common nosocomial infection and is associated with increased healthcare costs. In neonates, candida infection is associated with high mortality and morbidity and is transmitted by direct and indirect contact. Patient isolation measures, i.e. single room isolation or cohorting, are usually recommended for infections that spread by contact.

Objectives

To determine the effect of patient isolation measures (single room isolation and/or cohorting) for infants with candida colonization or infection as an adjunct to routine infection control measures on the transmission of candida to other infants in the neonatal unit.

Search methods

Relevant trials in any language were searched in the following databases in July 2011: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011), MEDLINE, BIOSIS, EMBASE and CINAHL. Proceedings of the Pediatric Academic Societies (from 1987) and ongoing trials were searched.

Selection criteria

  • Types of studies: Cluster randomized trials (where clusters may be defined by hospital, ward, or other subunits of the hospital).
  • Types of participants: Neonatal units caring for infants colonized or infected with Candida.
  • Types of interventions: A policy of patient isolation measures (single room isolation or cohorting of infants with Candida colonization or infection) compared to routine isolation measures.

Data collection and analysis

The standard methods of the Cochrane Neonatal Review Group (CNRG) were used to identify studies and to assess the methodological quality of eligible cluster-randomized trials. Infection rates and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used.

Results

  • No eligible trials were identified.

Authors' conclusions

The review found no evidence to either support or refute the use of patient isolation measures (single room isolation or cohorting) in neonates with candida colonization or infection.

Despite the evidence for transmission of candida by contact and evidence of cross-infection by health care workers, no standard policy of patient isolation measures beyond routine infection control measures exists in the neonatal unit. There is an urgent need to research the role of patient isolation measures for preventing transmission of candida in the neonatal unit. Well designed trials randomizing clusters of units or hospitals to a type of patient isolation method intervention are needed.

Plain language summary

Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units

Fungal infection with Candida has become increasingly common in the neonatal intensive care unit. Candida infection causes many deaths and significantly increases health care costs. Candida spreads among babies by contact, generally by health care staff and sometimes by family members. In addition to routine steps to control infection, keeping babies who have candida in separate rooms (single room isolation) or cared for together (cohorting) may decrease the spread of candida. In this review, the authors sought studies that evaluated these measures, but could not find any. Therefore, the authors recommend that appropriate studies be performed in the future to answer this important question that may save lives and costs.

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Background

Description of the condition

Candida has emerged as a common cause of infection in neonates (Beck-Sague 1993). In very low birth weight (VLBW, birth weight < 1500 g) infants, Candida albicans is the third most common cause (5.8%) of first episodes of late onset sepsis (LOS) (defined as sepsis after the first 72 hours of life) (Stoll 2002). The incidence of infections due to Candida varies inversely with the gestational age and birth weight (Saiman 2000; Stoll 2002). Candida infection is seen in 2.6% to 12.9% of VLBW infants (Baley 1984; Faix 1989; Saiman 2000) and 5.5% to 20% of ELBW infants (extremely low birth weight infants, birth weight < 1000 g) (Saiman 2000; Kaufman 2001). Although Candida albicans is the major Candida species isolated from neonates, infection with other species such as C. parapsilosis, C. tropicalis and fluconazole resistant C. glabrata is also increasing (Faix 1992; Kossoff 1998; Fairchild 2002). In a multicenter cohort study of 2847 infants, overall mortality in infants with candidemia was 22.9% (Saiman 2001). Systemic candidiasis is associated with an increase in hospital stay and duration of mechanical ventilation (Makhoul 2001). Candida infection and colonization is associated with significant health care costs, which are due to increased length of hospital stay, costs of antifungal therapy and associated co-morbidities (Miller 2001; Olaechea 2004).

Infection with candida can manifest as mucocutaneous or systemic candidiasis. Mucocutaneous candidiasis (MCC) may be defined as candidal infection of the skin and mucous membranes. MCC includes oral thrush, diaper dermatitis, congenital candidiasis and invasive fungal dermatitis that has the potential to spread into the blood or other tissues (Rowen 2003). Colonization can be defined as the presence of a microorganism in or on a host with growth and multiplication, but without any overt clinical expression or detected immune response in the host at the time the microorganism is isolated (Jarvis 1996). Use of third generation cephalosporins, central venous catheters, intravenous lipids and h3 receptor antagonists (ranitidine) are risk factors for C. albicans colonization, whereas delivery by cesarean section is protective (Saiman 2001). In a prospective study of 146 VLBW infants, fungal colonization was noted to be 26.7%; of those colonized; 28% developed mucocutaneous candidiasis and 7.7% developed systemic candidiasis (Baley 1986). Colonization has been noted to precede invasive fungal infection in neonates (Baley 1986; Huang 1998).

Transmission:
Transmission of C. albicans vertically from mother to the infant (Waggoner-Fountain 96) and nosocomial transmission of both albicans and non-albicans species of Candida has been documented (Pfaller 1998a; Pfaller 1998b). In addition to the endemic prevalence of Candida colonization and infection, epidemics or outbreaks with a single strain or multiple strains may be associated with clusters of infection in the neonatal unit (Khatib 1998). Health care staff may harbor Candida and be a source of infection. In one study of 2989 cultures from health care workers' hands, 5% were positive for C. albicans and 19% for C. parapsilosis (Saiman 2001). C. albicans and C. parapsilosis have been shown to survive on glass (three days), stainless steel (14 days), fabrics (14 days) and finger pads of volunteers (20% of C. albicans remained detectable one hour post-inoculation) for sufficient duration to cause cross infection (Traore 2002). Cross infection by health care workers causing outbreaks of C. albicans (Burnie 1985; Dorko 2001), C. parapsilosis (Huang 1999, Lupetti 2002), C. tropicalis (Finkelstein 1993) and C. lusitaniae (Fowler 1998) have been reported.

Description of the intervention

Infection control measures routinely employed in the neonatal unit include handwashing, using 'standard precautions' with all patient contact, caring for catheters in a manner that minimizes the risk of catheter contamination, optimizing nurse-patient ratios, avoiding overcrowding, and performing continuous monitoring and surveillance for nosocomial infection (Adams-Chapman 2002). The Center for Disease Control (CDC) recommends the use of 'standard precautions' consistently in all patients (Garner 1996b), which should be undertaken for blood, all body fluids, secretions and excretions, non-intact skin and mucous membranes. These precautions include handwashing, and the use of gloves, masks, gowns, eye and face shields. Unlike bacterial nosocomial infections, the efficacy of handwashing in the prevention of Candida transmission in the neonatal unit is not proven. In a study evaluating the efficacy of antiseptic soaps for handwashing in vitro against Candida species, germicidal chlorine with 5.25% sodium hypochlorite (Clorox), 4% chlorhexidene gluconate in alcohol (Hibiclens) and 10% povidone-iodine (Clinidine) were found to be effective but 3% para-meta-chloro-xylenol (Ultradex) was not (Silverman 1999). Use of alcohol based hand sanitizer was found to be as effective as conventional handwashing and induced better compliance in healthcare workers (Boyce 2002; Ng 2004; Larson 2005). In a systematic review evaluating the evidence for gowning in neonatal units, gowning was shown to have no effect on the incidence of systemic nosocomial infections, incidence of colonization or length of stay in the hospital (Webster 2003). The efficacy of each of the routine infection control measures alone is difficult to estimate, but an integrated approach that combines routine infection control measures with education and training of health care staff has been very effective in reducing neonatal nosocomial infections (Horbar 2004; Schelonka 2006).

How the intervention might work

Isolation and or cohorting may be effective in controlling nosocomial infections (Gastmeier 2004). It is clear that candida can be spread from patient to patient. Protective isolation by wearing gloves and gowns reduces nosocomial bacterial and fungal colonization, as well as the rate of infection in the Pediatric Intensive Care Unit (PICU) (Klein 1989). CDC guidelines recommend single room isolation for infections transmitted by contact (either directly or indirectly via equipment or other surfaces) (Garner 1996a; Garner 1996b). However, Neonatal Intensive Care Units (NICU) are often faced with lack of isolation rooms and/or health care personnel devoted to the care of babies in these isolation rooms. Isolation requirements may depend on factors including severity of illness in the infant, available resources and the transmissibility of the infection. Guidelines of the American Academy of Pediatrics (AAP) state that it may be unnecessary to isolate a neonate (except in the case of neonatal varicella-zoster or epidemic of bacterial infection) under the following conditions:

  1. there is sufficient medical and nursing staff on duty;
  2. sufficient space between stations;
  3. two or more sinks for handwashing available in each nursery area;
  4. continuing instruction is provided regarding the way infections spread (AAP 2002).

Cohorting is the physical segregation of infants in separate areas where newborns with similar exposures, colonization, or infections are cared for. Care is usually provided by designated staff assigned exclusively to these infants. Cohorting infants colonized or infected with pathogens that are transmissible by contact may be useful in controlling or reducing horizontal transmission of infection or colonization. Cohorting may be more feasible than single room isolation during outbreaks in the NICU setting. Cohorting does not require isolation rooms and may reduce resource utilization compared to single room isolation. However, the success of this system depends on the strict adherence of the health care staff to the cohort system (AAP 2002).

Isolation measures are extensively followed for infections and colonizations with methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus. Though generally thought to be effective, evidence from randomized controlled trials evaluating single room isolation and cohorting for MRSA colonization and infection is lacking. In a systematic review of isolation policies for MRSA colonization and infection, no randomized trials were identified (Cooper 2004). The prospective trials that were identified were of poor design with major confounding variables. Definite conclusions regarding the efficacy of isolation measures could not be drawn from this review. In a prospective, interrupted time-series study involving two centers, isolation of MRSA colonized patients in single rooms or cohorted bays in adult intensive care units did not reduce cross-infection (Cepeda 2005). However, a cluster-randomized trial would be the best means to evaluate the efficacy of patient isolation measures to prevent or reduce cross-infection.

Why it is important to do this review

The implications of the spread of candida infections in the neonatal unit, especially to VLBW and ELBW infants, are enormous. However, infection control measures can be expensive and consume valuable resources. It is not known whether the additional costs of these measures are worth the benefits in terms of reduction in the transmission of candida in the neonatal unit. There is a need for economic evaluation of infection control measures in the present cost conscious health care environment (Drummond 1991; Drummond 1996; Saint 2001). The effect of single room isolation or cohorting of candida colonized or infected infants as an adjunct to routine infection control measures on the transmission of candida in the neonatal unit and its economic implications has not been systematically reviewed.

Objectives

To determine the effect of patient isolation measures (single room isolation and cohorting) for infants with candida colonization or infection as an adjunct to routine infection control measures (which include standard precautions like handwashing, wearing protective clothing such as gloves and gowns and use of incubators) on the transmission of candida to other infants in the neonatal unit.

The following comparisons will be made:

Comparison 1: Patient isolation measures as an adjunct to routine infection control measures versus routine infection control measures

Subgroups within this comparison will be analyzed if data were available:

  1. single room isolation versus routine isolation measures;
  2. cohorting versus routine isolation measures.

Comparison 2: Single room isolation versus cohorting for infants used as adjuncts to routine infection control measures

Definitions

Colonization:

  1. Isolation of candida from the skin or mucous membranes without clinical manifestations.

Infection:

  1. Mucocutaneous candidiasis: clinical manifestation of skin and mucous membranes with isolation of Candida
  2. Systemic or invasive candidiasis: Isolation of candida in the blood, CSF (meningitis), urine obtained by suprapubic aspirate or by sterile catheterization (UTI) or from any other sterile site (e.g. pleural fluid, peritoneal fluid, intravascular devices, etc).

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Methods

Criteria for considering studies for this review

Types of studies

Cluster randomized trials (where clusters may be defined by hospital, ward, other subunits of the hospital).

Types of participants

Neonatal units (including Level III or intensive care unit and Level II or intermediate care unit) who have a policy for patient isolation measures for candida colonization and infection.

Types of interventions

A policy of patient isolation measures namely single room isolation or cohorting of infants with candida colonization or infection compared to routine isolation measures.

Operational definitions

Single room isolation: Isolation of an individual infant with candida colonization or infection in a separate room in the NICU with nursing personnel devoted to looking after the infant, until discharge or at least two negative surveillance cultures.

Cohorting: Physical segregation of infants with candida colonization or infection in a separate area in the NICU with infants with similar candida colonization or infection, with nursing personnel designated to looking after these cohorts until discharge or at least two negative surveillance cultures.

Routine measures: Measures other than 'single room isolation' or 'cohorting' already in place for control of transmission of infections in the NICU, including handwashing, use of 'standard precautions' with all patient contact, appropriate catheter care to minimize the risk of catheter contamination, optimizing nurse-patient ratio, avoiding overcrowding, and continuous monitoring and surveillance of nosocomial infection use of incubators among others.

Types of outcome measures

Primary outcome

Transmission of candida in the 'neonatal unit' as estimated by colonization and infection rates of candida in the neonatal unit (including Level III or intensive care unit and Level II or intermediate care unit).

Definitions of outcome measures (Harris 2001)

Infection rate will be presented as number of candida infections per 100 patients or 1000 patient days.
Colonization rate will be presented as number of candida colonization per 100 patients or 1000 patient days.

For both infection and colonization rates, the denominator will be all infants in the neonatal unit irrespective of candida colonization or infection status and colonization and infection rates will be tabulated separately.

Search methods for identification of studies

We used the search strategy of the Cochrane Neonatal Review Group. We searched relevant trials in any language in the following databases in July 2011:

  1. The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2011)
  2. Electronic journal reference databases -
    MEDLINE (1966 to July 2011) and PREMEDLINE
    EMBASE (1980 to July 2011)
    CINAHL (1982 to July 2011)
  3. Abstracts of conferences - Proceedings of the Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research) and the European Society for Pediatric Research (1987 to July 2011) were searched.
  4. Communication with authors for more information on relevant published articles or abstracts and with other prominent authors in the field for possible unpublished articles did not reveal any cluster randomized trial fitting the selection criteria.
  5. Additional searches were made in the reference lists of relevant journal articles and in the reviewer's personal files.

Search strategy for MEDLINE. This was adapted to suit EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials

  1. Explode 'candida' [MESH heading] /all subheadings
  2. Explode ''candidiasis" [MESH heading]/all subheadings
  3. Search 'mucocutaneous' near candid*
  4. Search 'cutaneous' near candid*
  5. Search candid* near colonization
  6. Search 'thrush'
  7. #1 OR #2 OR #3 OR #4 OR #5 OR #6
  8. Explode 'Infant-Newborn' [MESH heading]/ all subheadings
  9. neonat*
  10. #8 OR #9
  11. Search infect* near control*
  12. Search patient near isolation*
  13. Search 'communicable disease control'
  14. Search '(communicable adj disease adj control)'
  15. 'outbreak'
  16. 'epidemic'
  17. 'endemic'
  18. 'incidence'
  19. 'prevalence'
  20. 'screening'
  21. 'surveillance'
  22. 'coloniz*'
  23. 'colonis*'
  24. 'Isolation'
  25. 'Segregation'
  26. 'cohorting'
  27. 'economic*'
  28. Explode 'economics' [MESH heading]/all subheadings
  29. 'cost*'
  30. #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR
    #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29
  31. #7 AND #10 AND #30
  32. #31 and (TG=HUMAN)

No language restriction was applied.

Data collection and analysis

The standard methods of conducting Cochrane systematic reviews were used.

Selection of studies

The titles and the abstracts of studies identified by the search strategy were independently assessed for eligibility to be included into the review by the review authors PM and LW. If this could not be done reliably, then the full text version was obtained for assessment. Differences were resolved by discussion.

Data extraction and management

Forms were designed for trial inclusion/exclusion, data extraction and for requesting additional unpublished information from authors of the original reports. If eligible trials were identified, data extraction was to be done independently by the reviewer authors using specifically designed forms and compared for any differences.

Assessment of risk of bias in included studies

If eligible trials were identified, the standardized review methods of the Cochrane Neonatal Review Group (CNRG) were to be used to assess the methodological quality of the studies. Then the two review authors independently would have assessed the quality of the included studies using the standard criteria developed by the CNRG.

  1. Adequate (low risk of bias) allocation concealment
  2. Uncertainty about whether the allocation was adequately concealed
  3. Inadequate (high risk of bias) allocation concealment
  4. No allocation concealment

In addition, the following issues were to be reported:

  • Blinding of interventions
  • Blinding of outcome assessment
  • Completeness of follow-up of all randomized infants, irrespective of whether they received the allocated intervention or not (intention to treat basis)

If cluster randomized trials were identified, the methodological assessment would include whether the sample size was estimated based on the intracluster correlation co-efficient and whether the trial had been analyzed at the cluster level (the unit of randomization) and not at the individual level.

Measures of treatment effect

If eligible trials were identified, statistical analyses were to be performed according to the recommendations of the CNRG using the statistical package (RevMan 5.1) provided by the Cochrane Collaboration. Planned analyses were to be undertaken for the subgroups defined under the 'Criteria for considering studies for the review'. We planned to analyze categorical data using relative risk (RR), risk difference (RD) and the number needed to treat (NNT). We planned to analyze continuous data using weighted mean difference (WMD). We planned to report the 95% Confidence interval (CI) on all estimates.

Unit of analysis issues

In cluster-randomized trials, if the unit of analysis of the trial was the cluster (not individuals) and analysis took into account the correlation between clusters, the inverse variance method was to be used for meta-analysis. If this was not the case, a narrative synthesis was to be made without meta-analysis. Infection rates and colonization rates were to be expressed as rate ratios for each trial and if appropriate for meta-analysis, the generic inverse variance method in RevMan was to be used (Deeks 2004).

Assessment of heterogeneity

We planned to estimate the treatment effects of individual trials and examine heterogeneity between trials by inspecting the forest plots and quantifying the impact of heterogeneity using the I-squared statistic. If we detected statistical heterogeneity, we planned to explore the possible causes (for example, differences in study quality, participants, intervention regimens, or outcome assessments) using post hoc subgroup analyses. We planned to use a fixed effects model for meta-analysis.

Data synthesis

If appropriate, we planned to perform meta-analysis using Review Manager software (RevMan 5), supplied by the Cochrane Collaboration. For estimates of typical relative risk and risk difference, we planned to use the Mantel-Haenszel method. For measured quantities, we planned to use the inverse variance method. We planned to conduct all meta-analyses using the fixed effect model.

Subgroup analysis and investigation of heterogeneity

The following comparisons were planned:

Comparison 1: Patient isolation measures as an adjunct to routine infection control measures versus routine infection control measures

Subgroups within this comparison will be analyzed if data were available:

  1. single room isolation versus routine isolation measures;
  2. cohorting versus routine isolation measures.

Comparison 2: Single room isolation versus cohorting for infants used as adjuncts to routine infection control measures

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Results

Description of studies

No studies identified by our search strategy met our inclusion criteria and no ongoing trials were identified.

A study comparing nosocomial infection rate with a historical control nosocomial infection rate in a PICU was identified.

Excluded studies:

Ben-Abraham 2002
In a PICU redesigned from an open single space design to individual single rooms, nosocomial infection rate including candida infections significantly declined compared to historical nosocomial infection rates. However, this study compared prospectively gathered data to retrospective historical data, which could have introduced significant bias.

Risk of bias in included studies

Not applicable as there were no studies included.

Effects of interventions

No eligible trials were identified.

Discussion

No cluster randomized trial was identified that addressed the question of patient isolation measures beyond routine infection control measures, for infants colonized or infected with Candida, to prevent or reduce the transmission of candida in the neonatal unit. In addition, no published study reporting a neonatal unit's policy of patient isolation measures for infants colonized or infected with candida apart from routine infection control precautions were found.

The goal of any isolation measure is to prevent transmission of microorganisms from infected or colonized patients to other patients, hospital visitors, and healthcare workers and at the same time interfere minimally with patient care (Edmond 1997). The CDC recommends 'standard precautions' that apply to blood, all body fluids and secretions (except sweat), nonintact skin and mucous membranes for all patients and 'transmission based precautions' based on an individual agent's mode of transmission i.e. airborne, droplet or contact. For infections spread by direct or indirect contact, single room isolation or cohorting with patients infected or colonized with a similar organism is recommended (Garner 1996a; Garner 1996b). These isolation measures are commonly practiced for methicillin resistant S. aureus and vancomycin resistant enterococci infection or colonization. Though generally thought to be effective, the role of patient isolation measures in patients with MRSA colonization in reducing the transmission of infection in adult intensive care patients has recently been questioned (Cepeda 2005). Recommendations for patient isolation measures do not exist for candida infection and colonization in adult, pediatric or neonatal intensive care units.

Despite the fact that candida spreads by contact and candida colonization precedes invasive infection, patient isolation measures beyond routine infection control measures are not generally practiced. Handwashing remains the single most important measure in preventing nosocomial infections, but the efficacy of handwashing in preventing candida transmission by itself remains to be proven. There is scarce data to support or refute the use of patient isolation measures beyond routine infection control measures not only for candida, but also any other colonization or infection in any age group. In a PICU redesigned from an open single space design to individual single rooms, the rate of nosocomial infection including candida infection significantly declined compared to historical nosocomial infection rates. However, this study compared prospectively gathered data to retrospective historical data, which could have introduced significant bias (Ben-Abraham 2002).

Nevertheless, given the high mortality and morbidity after Candida infections in critically ill neonates (Saiman 2001; Makhoul 2001), a strong case exists for neonatal units to develop a policy for patient isolation measures for Candida infection and colonization. Any policy developed will have to be subjected to rigorous testing not only for efficacy but also for cost-effectiveness. In general, candida infections are one of the most common nosocomial bloodstream infections in the United States (NNIS 2001), with an attributable mortality of 20 to 50% in adults (Gudlaugsson 2003; Morgan 2005). The incidence of nosocomial candidemia in all ages is estimated close to 8/100, 000 population (NNIS 2001) and hospital costs approaching $ 1billion/yr (Miller 2001). This makes a strong case for interventions to reduce nosocomial candida infections. Patient isolation measures (i.e. single room isolation and cohorting) beyond standard precautions or routine infection control measures should be tested for efficacy in preventing or reducing nosocomial candida infections and for cost-effectiveness.

The most appropriate method to rigorously test the above hypotheses would be to design cluster randomized trials involving multiple units or hospitals with randomized allocation to one type of patient isolation measure or the other (i.e. single room isolation or cohorting). Cluster randomized trials are more complex than randomized control trials and care should be taken during design and execution so that potential biases are avoided (Puffer 2003). Due consideration should be given to the unique analyses required in cluster randomized controlled trials (Campbell 1998; Murray 2004; Goodacre 2005). The importance of standardized reporting of results of cluster-randomized trials cannot be overemphasized (Puffer 2003).

Authors' conclusions

Implications for practice

The review found no evidence to either support or refute the use of patient isolation measures (single room isolation or cohorting) in neonates with candida colonization or infection. Despite the evidence for direct or indirect contact transmission of candida and evidence of cross-infection by health care workers, no standard policy of patient isolation measures beyond routine infection control measures exists in neonatal units.

Implications for research

Given the rapid emergence of candida infections and the high mortality and morbidity associated with these infections in the neonatal unit, there is an urgent need to establish or refute a role for patient isolation measures (single room isolation or cohorting) beyond standard precautions for preventing transmission of candida. Cluster randomized trials involving multiple units or hospitals with randomized allocation of one type of patient isolation measure or the other (i.e. single room isolation or cohorting) with careful consideration for determining an appropriate sample size and analysis would be the most appropriate method to research this question.

Acknowledgements

We acknowledge the help of Stavrous Petrou, Health Economist at the National Perinatal Epidemiology Unit, Oxford, U.K. for comments on the review.

Contributions of authors

Dr. Pammi reviewed the literature, wrote the protocol, searched for studies, reviewed studies and completed the review.

Dr. Weisman assisted in the preparation of the protocol, reviewed studies and assisted in the writing of the review.

Mr. Eddama commented on and assisted with the health economics content of the review.

Declarations of interest

  • None noted.

Differences between protocol and review

  • None noted.

Additional tables

  • None noted.

Potential conflict of interest

Characteristics of Included Studies

  • None noted.

Characteristics of excluded studies

Ben-Abraham 2002

Reason for exclusion

Not a neonatal study or a randomized trial

Characteristics of studies awaiting classification

  • None noted.

Characteristics of ongoing studies

  • None noted.

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References to studies

Included studies

  • None noted.

Excluded studies

Ben-Abraham 2002

Ben-Abraham R, Keller N, Szold O, Vardi A, Weinberg M, Barzilay Z et al. Do isolation rooms reduce the rate of nosocomial infections in the pediatric intensive care unit? Journal of Critical Care 2002;17:176-80.

Studies awaiting classification

  • None noted.

Ongoing studies

  • None noted.

Other references

Additional references

AAP 2002

AAP, ACOG. Guidelines for Perinatal Care. Fifth edition. Washington DC: American Academy of Pediatrics, 2002.

Adams-Chapman 2002

Adams-Chapman I, Stoll BJ. Prevention of nosocomial infections in the neonatal intensive care unit. Current Opinion in Pediatrics 2002;14:157-64.

Baley 1984

Baley JE, Kliegman RM, Fanaroff AA. Disseminated fungal infections in very low-birth-weight infants: therapeutic toxicity. Pediatrics 1984;73:153-7.

Baley 1986

Baley JE, Kliegman RM, Boxerbaum B, Fanaroff AA. Fungal colonization in the very low birth weight infant. Pediatrics 1986;78:225-32.

Beck-Sague 1993

Beck-Sague C, Jarvis WR. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980-1990. National Nosocomial Infections Surveillance System. Journal of Infectious Diseases 1993;167:1247-51.

Boyce 2002

Boyce JM, Pittet D. Guidelines for hand hygiene in health-care settings. MMWR 2002;51:1-44.

Burnie 1985

Burnie JP, Odds FC, Lee W, Webster C, Williams JD. Outbreak of systemic Candida albicans in intensive care unit caused by cross infection. British Medical Journal (Clinical Research Ed) 1985;290:746-8.

Campbell 1998

Campbell MK, Grimshaw JM. Cluster randomised trials: time for improvement. The implications of adopting a cluster design are still largely being ignored. BMJ 1998;317:1171-2.

Cepeda 2005

Cepeda JA, Whitehouse T, Cooper B, hails J, Jones K, Kwaku F et al. Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive care units: prospective two-centre study. Lancet 2005;365:295-304.

Cooper 2004

Cooper BS, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Medley GF et al. Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of literature. BMJ 2004;329:533.

Deeks 2004

Deeks JJ, Higgins, JPT, Altman DG, editors. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005]; Section 8: Analysing and presenting results. The Cochrane Library Cochrane 2005;(1).

Dorko 2001

Dorko E, Viragova S, Jautova J, Pilipcinec E, Danko J, Svicky E. Electrophoretic karyotyping of Candida albicans strains isolated from premature infants and hospital personnel in a neonatal intensive care unit. Folia Microbiologica (Praha) 2001;46:453-7.

Drummond 1991

Drummond MF, Davies LM. Evaluation of the costs and benefits of reducing hospital infection. Journal of Hospital Infection 1991;18 Suppl A:85-93.

Drummond 1996

Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. British Medical Journal 1996;313:275-83.

Edmond 1997

Edmond MP. Isolation. Infection Control and Hospital Epidemiology 1997;18:58-64.

Fairchild 2002

Fairchild KD, Tomkoria S, Sharp EC, Mena FV. Neonatal Candida glabrata sepsis. Clinical and laboratory features compared with other Candida species. Pediatric Infectious Disease Journal 2002;21:39-43.

Faix 1989

Faix RG, Kovarik SM, Shaw TR. Mucocutaneous and invasive candidiasis among very low birthweight (less than 1, 500 grams) infants in intensive care nurseries:a prospective study. Pediatrics 1989;83:101-7.

Faix 1992

Faix RG. Invasive neonatal candidiasis: comparison of albicans and parapsilosis infection. Pediatric Infectious Disease Journal 1992;11:88-93.

Finkelstein 1993

Finkelstein R, Reinhertz G, Hashman N, Merzbach D. Outbreak of Candida tropicalis fungemia in a neonatal intensive care unit. Infection Control and Hospital Epidemiology 1993;14:587-90.

Fowler 1998

Fowler SL, Rhoton B, Springer SC, Messer SA, Hollis RJ, Pfaller MA. Evidence for person-to-person transmission of Candida lusitaniae in a neonatal intensive-care unit. Infection Control and Hospital Epidemiology 1998;19:343-5.

Garner 1996a

Garner JS. Guideline for isolation precautions in hospitals. Part I. Evolution of isolation practices, Hospital Infection Control Practices Advisory Committee. American Journal of Infection Control 1996;24:24-31.

Garner 1996b

Garner JS. Guideline for isolation precautions in hospitals. The Hospital Infection Control Practices Advisory Committee. Infection Control and Hospital Epidemiology 1996;17:53-80.

Gastmeier 2004

Gastmeier P, Schwab F, Geffers C, Ruden H. To isolate or not to isolate? Analysis of data from the German Nosocomial Infection Surveillance System regarding the placement of patients with methicillin-resistant Staphylococcus aureus in private rooms in intensive care units. Infect Control Hosp Epidemiol 2004;25:109-13.

Goodacre 2005

Goodacre S. Appropriate analysis and reporting of cluster randomised trials. Emergency Medicine Journal 2005;22:156.

Gudlaugsson 2003

Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J, Messer et al. Attributable mortality of nosocomial candidemia, revised. Clinical Infectious Diseases 2003;37:1172-7.

Harris 2001

Harris JS, Goldmann DA. Infections acquired in the nursery: Epidemiology and control. In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, London, Toronto, New York, St. Louis, Sydney: WB Saunders & Company, 2001:1371-1418.

Horbar 2004

Horbar JD, Carpenter JH, Buzas J, Soll RF, Suresh G, Bracken MB et al. Collaborative quality improvement to promote evidence based surfactant for preterm infants: a cluster randomised trial. BMJ 2004;329:1004.

Huang 1998

Huang YC, Li CC, Lin TY, Lien RI, Chou YH, Wu JL et al. Association of fungal colonization and invasive disease in very low birth weight infants. Pediatric Infectious Disease Journal 1998;17:819-22.

Huang 1999

Huang YC, Lin TY, Leu HS, Peng HL, Wu JH, Chang HY. Outbreak of Candida parapsilosis fungemia in neonatal intensive care units: clinical implications and genotyping analysis. Infection 1999;27:97-102.

Jarvis 1996

Jarvis WR. The epidemiology of colonization. Infection Control and Hospital Epidemiology 1996;17:47-52.

Kaufman 2001

Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Donowitz LG. Fluconazole prophylaxis against fungal colonization and infection in preterm infants. New England Journal of Medicine 2001;345:1660-6.

Khatib 1998

Khatib R, Thirumoorthi MC, Riederer KM, Sturm L, Oney LA, Baran J Jr. Clustering of Candida infections in the neonatal intensive care unit: concurrent emergence of multiple strains simulating intermittent outbreaks. Pediatric Infectious Disease Journal 1998;17:130-4.

Klein 1989

Klein BS, Perloff WH, Maki DG. Reduction of nosocomial infection during pediatric intensive care by protective isolation. New England Journal of Medicine 1989;320:1714-21.

Kossoff 1998

Kossoff EH, Buescher ES, Karlowicz MG. Candidemia in a neonatal intensive care unit: trends during fifteen years and clinical features of 111 cases. Pediatric Infectious Disease Journal 1998;17:504-8.

Larson 2005

Larson EL, Cimiotti J, Haas J, Parides M, Nesin M, Della-Latta P, Saiman L. Effect of antiseptic handwashing vs alcohol sanitizer on health-care associated infections in neonatal intensive care units. Archives of Pediatric and Adolescent Medicine 2005;159:377-83.

Lupetti 2002

Lupetti A, Tavanti A, Davini P, Ghelardi E, Corsini V, Merusi I et al. Horizontal transmission of Candida parapsilosis candidemia in a neonatal intensive care unit. Journal of Clinical Microbiology 2002;40:2363-9.

Makhoul 2001

Makhoul IR, Kassis I, Smolkin T, Tamir A, Sujov P. Review of 49 neonates with acquired fungal sepsis: further characterization. Pediatrics 2001;107:61-6.

Miller 2001

Miller LG, Hajjeh RA, Edwards JE Jr. Estimating the cost of nosocomial candidemia in the United States. Clinical Infectious Diseases 2001;32:1110.

Morgan 2005

Morgan J, Meltzer MI, Plikyatis BD, Sofair AN, Huie-White S, Wilcox S et al. Excess mortality, hospital stay and cost due to candidemia: a case-control study using data from population-based candidemia surveillance. Infection Control and Hospital Epidemiology 2005;26:540-7.

Murray 2004

Murray DM, Varnell SP, Blitstein JL. Design and analysis of group-randomized trials: A review of recent methodological developments. American Journal of Public Health 2004;94:423-32.

Ng 2004

Ng PC, Wong HL, Lyon DJ, So KW, Liu F, Lam RK, Wong E, et al. Combined use of alcohol hand rub and gloves reduces the incidence of late onset infection in very low birth weight infants. Archives of Disease in Childhood Fetal Neonatal Ed 2004;89:F336-40.

NNIS 2001

Centers for Disease Control and Prevention. National Nosocomial Infections Surveillance (NNIS) System Report, Data Summary from January 1992-June 2001, issued August 2001. American Journal of Infection Control 2001;29:404-21.

Olaechea 2004

Olaechea PM, Palomar M, Leon-Gil C, Alvarez-Lerma F, Jorda R, Nolla-Salas J, Leon-Regidor MA; EPCAN study group. Economic impact of Candida colonization and Candida infection in the critically ill patient. European Journal of Clinical Microbiology and Infectious Diseases 2004;23:323-30.

Pfaller 1998a

Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic. Diagnostic Microbiology and Infectious Disease 1998;30:121-9.

Pfaller 1998b

Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagnostic Microbiology and Infectious Disease 1998;31:327-32.

Puffer 2003

Puffer S, Torgerson D, Watson J. Evidence for risk bias in cluster randomised trials: review of recent trials published in three general medical journals. BMJ 2003;327:785-9.

Rowen 2003

Rowen JL. Mucocutaneous candidiasis. Seminars in Perinatology 2003;27:406-13.

Saiman 2000

Saiman L, Ludington E, Pfaller M, Rangel-Frausto S, Wiblin RT, Dawson J et al. Risk factors for candidemia in Neonatal Intensive Care Unit patients. Pediatric Infectious Disease Journal 2000;19:319-24.

Saiman 2001

Saiman L, Ludington E, Dawson JD, Patterson JE, Rangel-Frausto S, Wiblin RT et al. Risk factors for Candida species colonization of neonatal intensive care unit patients. Pediatric Infectious Disease Journal 2001;20:1119-24.

Saint 2001

Saint S, Chenoweth C, Fendrick AM. The role of economic evaluation in infection control. American Journal of Infection Control 2001;29:338-44.

Schelonka 2006

Schelonka RL, Scruggs S, Nichols K, Dimmit RA, Carlo WA. Sustained reductions in neonatal nosocomial infection rates following a comprehensive infection control intervention. Journal of Perinatology 2006;26:176-9.

Silverman 1999

Silverman J, Vazquez JA, Sobel JD, Zervos MJ. Comparative in vitro activity of antiseptics and disinfectants versus clinical isolates of Candida species. Infection Control and Hospital Epidemiology 1999;20:676-84.

Stoll 2002

Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002;110 (2 Pt 1):285-91.

Traore 2002

Traore O, Springthorpe VS, Sattar SA. A quantitative study of the survival of two species of Candida on porous and non-porous environmental surfaces and hands. Journal of Applied Microbiology 2002;92:549-55.

Waggoner-Fountain 96

Waggoner-Fountain LA, Walker MW, Hollis RJ, Pfaller MA, Ferguson JE 2nd, Wenzel RP et al. Vertical and horizontal transmission of unique Candida species to premature newborns. Clinical Infectious Diseases 1996;22:803-8.

Webster 2003

Webster J, Pritchard MA. Gowning by attendants and visitors in newborn nurseries for prevention of neonatal morbidity and mortality. Cochrane Database of Systematic Reviews 2003, Issue 3. Art. No.: CD003670. DOI: 10.1002/14651858.CD003670.

Other published versions of this review

Pammi 2007

Pammi M, Eddama O, Weisman LE. Patient isolation measures for infants with candida colonization or infection for preventing or reducing transmission of candida in neonatal units. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD006068. DOI: 10.1002/14651858.CD006068.pub2.

Classification pending references

  • None noted.

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Data and analyses

  • None noted.

Sources of support

Internal sources

  • None noted.

External sources

  • None noted.

This review is published as a Cochrane review in The Cochrane Library, Issue 11, 2011 (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 version of the review.