title: Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants.
abstract: BACKGROUND
  Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.
  
  
  OBJECTIVE
  To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants.
  
  
  METHODS
  We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews.
  
  
  METHODS
  Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants.
  
  
  METHODS
  We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.
  
  
  RESULTS
  Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical risk ratio 0.20 (95% confidence interval 0.14 to 0.27); risk difference -0.18 (-0.21 to -0.16)] but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality [typical risk ratio 0.87 (0.72 to 1.05); risk difference -0.03 (-0.06 to 0.01)]. None of the trials assessed posthospital discharge outcomes.Two trials (N = 265) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality.
  
  
  CONCLUSIONS
  The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.
authors.affiliation: NICU, Christchurch Womens Hospital, Christchurch, New Zealand. nicola.austin@cdhb.govt.nz
authors.forename: Nicola
authors.initials: N
authors.lastname: Austin
authors.forename: Brian A
authors.initials: BA
authors.lastname: Darlow
authors.forename: William
authors.initials: W
authors.lastname: McGuire
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000935:Antifungal Agents / Q000627:therapeutic use*; D015725:Fluconazole / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D008825:Miconazole / Q000627:therapeutic use; D009181:Mycoses / Q000517:prevention & control*; D009761:Nystatin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
chemical_list: D000935:Antifungal Agents; D009761:Nystatin; D008825:Miconazole; D015725:Fluconazole