Published online April 3, 2006
PEDIATRICS Vol. 117 No. 4 April 2006, pp. 1243-1252 (doi:10.1542/peds.2005-1969)

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Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants

Smart Uko, MD^a, Lamia M. Soghier, MB, ChB^a, Melissa Vega, PA-C^a, Jeremy Marsh, CET, CPT^a, Gerald T. Reinersman, MD^a, Lucille Herring, RN, MS, CIC^a,b, Viral A. Dave, MD^a, Suhas Nafday, MD^a and Luc P. Brion, MD^a

^a Department of Pediatrics, Division of Neonatology
^b Department of Infectious Diseases, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, New York

OBJECTIVES. To assess whether targeted short-term fluconazole prophylaxis reduces late-onset (>3 days of age) invasive fungal infection (IFI) among very low birth weight infants and extremely low birth weight (ELBW) infants and to assess mortality rates, toxicity, and costs associated with this intervention.

METHODS. An observational study of 2 subsequent epochs of inborn infants with birth weight of <1500 g or gestational age of <32 weeks, 1 before (control) and 1 after (fluconazole) initiation of routine targeted fluconazole prophylaxis in March 2003, was performed. Targeted fluconazole (3 mg/kg) prophylaxis was administered to infants for whom a decision was made to administer broad-spectrum antibiotics for >3 days.

RESULTS. IFI was observed for 13 (6.3%) of 206 infants in the control epoch and 2 (1.1%) of 178 in the fluconazole epoch, with a common odds ratio of 0.166. Logistic regression analysis taking into account all published factors (except for fungal colonization) showed that the fluconazole epoch was associated significantly with lower IFI rates. We observed no change in late (>3 days) mortality rates (11 of 206 infants in the control epoch vs 8 of 178 infants in the prophylaxis epoch). The mortality rate for ELBW infants with IFI was low (15%) in our study. Fluconazole was administered to 81% of ELBW infants, who received a median of 8 doses, and 41% of larger infants, who received a median of 5 doses. The intervention was cost-effective, and the effective number needed to treat to prevent 1 IFI was 10.

CONCLUSIONS. This study suggests that targeted short-course fluconazole prophylaxis in very low birth weight and ELBW infants may be efficacious and cost effective.

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Key Words: very low birth weight • extremely low birth weight • preterm • fluconazole • prophylaxis • invasive fungal infection • logistic regression analysis • Candida parapsilosis • Candida albicans • Candida lusitaniae

Abbreviations: BW—birth weight • CI—confidence interval • CRIB—Clinical Risk Index for Babies • ELBW—extremely low birth weight • GA—gestational age • IFI—invasive fungal infection • IQR—interquartile range • LOS—length of stay • NEC—necrotizing enterocolitis • NNT—number needed to treat • OR—odds ratio • RR—relative risk • VLBW—very low birth weight • MIC—minimal inhibitory concentration • NICHD—National Institute of Child Health and Human Development

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Accepted Oct 11, 2005.

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