Fluconazole and Cholestasis

Aghai ZH, Mudduluru M, Nakhla TA, et al. Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis. Journal of Perinatology (2006) 26, 550–555. Full Text | PDF

Background: Extremely low birth weight (ELBW) infants are at increased risk for invasive candidiasis and associated morbidity and mortality. The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians.

Objectives: To evaluate the effectiveness and safety of fluconazole prophylaxis in ELBW infants.

Study design: ELBW infants (BW

1000 g) born during the pre-prophylaxis era (PPE, January 1998–February 2002) were compared with prophylaxis era (PE, March 2002–September 2005). Infants born during PE received fluconazole prophylaxis for 6 weeks, as long as they had intravenous access. Demographic and clinical data were collected. The two groups were compared for baseline demographics, risk factors for candidiasis, the incidence of invasive candidiasis, liver enzymes, alkaline phosphatase, and bilirubin (total and direct).

Results: Nine out of 137 infants (6.6%) developed invasive candidiasis during PPE compared to none of 140 (0%) during PE (P=0.006). During PE, 60/140 (42.9%) infants developed conjugated hyperbilirubinemia compared to 12/137 (8.8%) during PPE (P<0.001).

Conclusion: Although a fluconazole prophylaxis regimen for ELBW infants was effective in preventing invasive candidiasis, an increase in the incidence of conjugated hyperbilirubinemia was observed. Further studies are needed to evaluate the safety of fluconazole prophylaxis in this population.

Comments. The major drawbacks of this study are the retrospective design and the use of historical controls. The study findings do not prove and cause and effect relationship between fluconazole use and cholestasis in these patients. Furthermore, the cholestasis was usually mild and resolved before discharge. This report adds more support for the efficacy of fluconazole prophylaxis for preventing candida infections in ELBW patients. I think the relative risk of Candida sepsis is much worse than the risk of possible cholestasis in this population, at least in our NICU. ABK.

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