Prophylactic systemic antifungal agents to prevent mortality and morbidity in
very low birth weight infants.
Author(s): Austin N(1), McGuire W.
Affiliation(s): Author information:
(1)NICU, Christchurch Womens Hospital, Christchurch, New Zealand.
Publication date & source: 2013, Cochrane Database Syst Rev. , 4:CD003850
BACKGROUND: Invasive fungal infection is an important cause of mortality and
morbidity in very low birth weight infants. Early diagnosis is difficult and
treatment is often delayed. Systemic antifungal agents (usually azoles) are
increasingly used as prophylaxis against invasive fungal infection.
OBJECTIVES: To assess the effect of prophylactic systemic antifungal therapy on
mortality and morbidity in very low birth weight infants.
SEARCH 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.
SELECTION CRITERIA: Randomised controlled trials or quasi-randomised controlled
trials that compared the effect of prophylactic systemic antifungal therapy
versus placebo or no drug or another antifungal agent or dose regimen in very low
birth weight infants.
DATA COLLECTION AND ANALYSIS: 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.
MAIN RESULTS: We identified 11 eligible trials enrolling a total of 1136 infants.
Seven trials (involving 880 infants) compared systemic antifungal prophylaxis
versus placebo or no drug. These trials were generally small but of good
methodological quality. Meta-analysis found a statistically significant reduction
in the incidence of invasive fungal infection in infants who received systemic
antifungal prophylaxis (typical risk ratio (RR) 0.41, 95% confidence interval
(CI) 0.27 to 0.61; risk difference (RD) -0.09, 95% CI -0.14 to -0.05). The
average incidence of invasive fungal infection in the control groups of the
trials (16%) was much higher than that generally reported from large cohort
studies (< 5%). Meta-analysis did not find a statistically significant difference
in the risk of death prior to hospital discharge (typical RR 0.74, 95% CI 0.52 to
1.05; RD -0.04, 95% CI -0.08 to 0.01). Very limited data on long-term
neurodevelopmental outcomes were available. Two trials that compared systemic
versus oral or topical non-absorbed antifungal prophylaxis did not detect any
statistically significant effects on invasive fungal infection or mortality. Two
trials that compared different dose regimens of prophylactic intravenous
fluconazole did not detect any significant differences in infection rates or
mortality.
AUTHORS' CONCLUSIONS: Prophylactic systemic antifungal therapy reduces the
incidence of invasive fungal infection in very low birth weight infants. This
finding should be interpreted and applied cautiously since the incidence of
invasive fungal infection was very high in the control groups of most of the
included trials. Meta-analysis does not demonstrate a statistically significant
effect on mortality. There are currently only limited data on the long-term
neurodevelopmental consequences for infants exposed to this intervention. In
addition, there is a need for further data on the effect of the intervention on
the emergence of organisms with antifungal resistance.
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