Fluconazole prophylaxis against fungal colonization and infection in preterm infants

Background: Invasive fungal infection is associated with substantial morbid ity and mortality in preterm infants. We evaluated the efficacy of prophyla ctic fluconazole in preventing fungal colonization and invasive infection i n extremely-low-birth-weight infants. Methods: We conducted a prospective, randomized, double-blind clinical tria l over a 30-month period in 100 preterm infants with birth weights of less than 1000 g. The infants were randomly assigned during the first five days of life to receive either intravenous fluconazole or placebo for six weeks. We obtained weekly surveillance cultures from all patients. Results: The 50 infants randomly assigned to fluconazole and the 50 control infants were similar in terms of birth weight, gestational age at birth, a nd base-line risk factors for fungal infection. During the six-week treatme nt period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; dif ference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.00 2). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the pla cebo group (20 percent) and none of the infants in the fluconazole group (d ifference in risk, 0.20; 95 percent confidence interval, 0.04 to 0.36; P=0. 008). The sensitivities of the fungal isolates to fluconazole did not chang e during the study, and no adverse effects of the fluconazole therapy were documented. Conclusions: Prophylactic administration of fluconazole during the first si x weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g. (N Eng l J Med 2001;345:1660-6.) Copyright (C) 2001 Massachusetts Medical Society.