Fluconazole prophylaxis against fungal colonization and infection in preterm infants

N Engl J Med. 2001 Dec 6;345(23):1660-6. doi: 10.1056/NEJMoa010494.


Background: Invasive fungal infection is associated with substantial morbidity and mortality in preterm infants. We evaluated the efficacy of prophylactic fluconazole in preventing fungal colonization and invasive infection in extremely-low-birth-weight infants.

Methods: We conducted a prospective, randomized, double-blind clinical trial 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, and base-line risk factors for fungal infection. During the six-week treatment period, fungal colonization was documented in 30 infants in the placebo group (60 percent) and 11 infants in the fluconazole group (22 percent; difference in risk, 0.38; 95 percent confidence interval, 0.18 to 0.56; P=0.002). Invasive fungal infection with positive growth of fungal isolates from the blood, urine, or cerebrospinal fluid developed in 10 infants in the placebo group (20 percent) and none of the infants in the fluconazole group (difference 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 change during the study, and no adverse effects of the fluconazole therapy were documented.

Conclusions: Prophylactic administration of fluconazole during the first six weeks of life is effective in preventing fungal colonization and invasive fungal infection in infants with birth weights of less than 1000 g.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use*
  • Bacterial Infections / epidemiology
  • Candida / drug effects
  • Candida / isolation & purification
  • Candida albicans / drug effects
  • Candida albicans / isolation & purification
  • Candidiasis / prevention & control
  • Colony Count, Microbial
  • Double-Blind Method
  • Fluconazole / adverse effects
  • Fluconazole / therapeutic use*
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / prevention & control*
  • Infant, Very Low Birth Weight*
  • Infusions, Intravenous
  • Microbial Sensitivity Tests
  • Mycoses / prevention & control*
  • Prospective Studies
  • Trichosporon / isolation & purification


  • Antifungal Agents
  • Fluconazole