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 (< 32 weeks gestation) or very low birth weight (VLBW) infants. Clinical uncertainly 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.
Objectives
To assess the effect of prophylactic oral/topical non‐absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in VLBW infants.
Search methods
The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 ‐ May 2009), EMBASE (1980 ‐ May 2009), conference proceedings, and previous reviews.
Selection criteria
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 VLBW infants.
Data collection and analysis
Data were extracted using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by each review author and synthesis of data using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD).
Main results
Three trials, in which a total of 1625 infants participated, have 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 two of the included trials. Meta‐analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical RR 0.19 (95% confidence interval (CI) 0.14, 0.27); typical RD ‐0.19 (95% CI ‐0.22,‐0.16)] but substantial statistical heterogeneity was detected. A statistically significant effect on mortality was not found [typical RR 0.88 (95% CI 0.72, 1.06); typical RD ‐0.02 (95% CI ‐0.06, 0.01)]. Long‐term outcomes were not assessed by any of the trials.
One small trial (N = 21) that assessed the effect of oral/topical non‐absorbed antifungal prophylaxis (nystatin) compared with systemic antifungal (fluconazole) prophylaxis was underpowered to exclude important clinical effects.
Authors' conclusions
The finding of a reduction in risk of invasive fungal infection in 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.
PICOs
Plain language summary
Prophylactic oral/topical non‐absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants.
Fungi such as candida (the organism that causes thrush) can cause severe infections in very low birth weight (VLBW) infants (birth weight less than 1.5 kilograms). These infections are often difficult to diagnose and frequently cause death or disability. Therefore, it may be appropriate to attempt to prevent such infections by giving VLBW infants antifungal drugs as a routine part of their care. This review assessed the effect of giving VLBW infants antifungal drugs that reduce skin and gut carriage of fungi to minimise the chances of a severe infection developing. The trials that were identified suggested that this treatment might reduce severe infection rates but there was no evidence that death rates were reduced. Larger and higher quality trials are needed to resolve this uncertainty.
