Review question: In very low birth weight infants, does the use of prophylactic systemic antifungal therapy decrease the risk of mortality and morbidity?
Background: Fungi such as candida (the organism that causes thrush) can cause severe infections in very low birth weight infants (birth weight less than 1.5 kg). These infections are often difficult to diagnose. It may be appropriate to attempt to prevent such infections by giving all very low birth weight infants antifungal drugs as a routine part of their care (systemic antifungal prophylaxis). This review assessed whether evidence exists that such a practice prevents severe fungal infection, death, and disability in very low birth weight infants.
Study characteristics: We identified 15 eligible trials enrolling a total of 1690 infants. These trials were generally of good quality.
Key findings: The overall analysis showed a reduction in the risk of severe fungal infection in infants who received systemic antifungal prophylaxis but did not show a difference in the risk of death. The trials did not assess the risk of long-term problems, including disabilities.
Conclusions: There is evidence from some good-quality trials that giving infants an antifungal drug regularly for the first four to six weeks after birth reduces the number of infants who develop severe infection. There is not yet any convincing evidence that death or disability rates are affected.
Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very preterm or 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 many 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.
Invasive fungal infection is an important cause of mortality and morbidity in very preterm and very low birth weight infants. Early diagnosis is difficult and treatment is often delayed. Systemically absorbed antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection in this population.
To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very preterm or very low birth weight infants.
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 2015, Issue 8), MEDLINE, EMBASE, and CINAHL (to May 2015), conference proceedings, and previous reviews.
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.
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.
We identified 15 eligible trials enrolling a total of 1690 infants. Ten trials (1371 infants) compared systemic antifungal prophylaxis versus placebo or no drug. These trials were generally of good methodological quality. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection (typical risk ratio (RR) 0.43, 95% confidence interval (CI) 0.31 to 0.59; risk difference (RD) −0.09, 95% CI −0.12 to −0.06). 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. Meta-analysis did not find a statistically significant difference in the risk of death prior to hospital discharge (typical RR 0.79, 95% CI 0.61 to 1.02; typical RD −0.04, 95% CI −0.07 to 0.00). Very limited data on long-term neurodevelopmental outcomes were available. Three 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.