Fluconazole Prophylaxis Decreases the Combined Outcome of Invasive Candida Infections or Mortality in Preterm Infants: In Reply

Abstract

We thank Dr Kaufman for his comments regarding the safety and efficacy of fluconazole prophylaxis in preventing invasive Candida infections in infants weighing <1000 g at birth. We concur that the evidence from published, randomized, controlled trials (both single and multicenter) strongly supports this approach as a means to prevent Candida-associated death or neurodevelopmental impairment that occurs in almost three quarters of Candida-infected preterm infants.1 In addition, while being cognizant of the limitation of their retrospective study design, 7 single-center cohort studies with retrospective controls have all demonstrated a reduction in Candida infections and associated deaths through the use of fluconazole prophylaxis. No randomized, controlled trial or retrospective cohort study has reported any fluconazole-attributable adverse events that persisted past hospital discharge. In addition, although justifiable concern for the emergence of fluconazole-resistant Candida species in the NICU has been voiced, this has not been demonstrated to date.2–4The majority of infants given fluconazole prophylaxis in all studies reported to date used birth weights of <1000 g as an inclusion criterion.2 We agree that rates of invasive Candida infections are considerably higher in infants weighing <750 g and that these infants also are at highest risk of poor outcome. However, the risks of invasive Candida infections in infants with birth weights between 750 and 1000 g are not trivial, and these infants also are likely to have ongoing risk factors that enhance their risk of acquiring infection beyond several weeks of life.1Undoubtedly, there are unanswered questions regarding which preterm infants will benefit most from fluconazole prophylaxis. There are approaches that deserve further study, such as targeting infants with different birth weights and gestation, confining prophylaxis to time periods of highest risk, or, conversely, prolonging prophylaxis for infants with ongoing risk factors. Although we agree that such studies are needed, we believe that there are sufficiently strong data to consider fluconazole prophylaxis for infants weighing <1000 g in NICUs in which incidence exceeds 5% and adherence to infection control measures is high.