SAN FRANCISCO — Fluconazole prophylaxis twice weekly during the first 6 weeks of life is similar to the previously studied schedule of more frequent doses in preventing invasive fungal infection in high-risk preterm infants who weigh less than 1,000 g at birth, David Kaufman, M.D., reported at the annual meeting of the Pediatric Academic Societies.
“This dosing seems comparable,” Dr. Kaufman said in a later interview. “Certainly, [it] offers the benefit of less cost and less patient exposure as far as potential side effects. The bigger issue is that some fungi develop resistance to fluconazole. This [dosing] is another way to reduce the possibility of resistance.”
Dr. Kaufman and his associates conducted a 2-year prospective, randomized, double-blind study of 81 high-risk preterm infants at the University of Virginia Children's Medical Center, Charlottesville.
The infants had birth weights of less than 1,000 g and either an endotracheal tube or central venous catheter. Infants were randomized to receive one of two dosing schedules. Dosing schedule A consisted of 3 mg of intravenous fluconazole per kilogram of body weight every 72 hours during weeks 1 and 2, then every 48 hours during weeks 3 and 4, and every 24 hours for weeks 5 and 6. Dosing schedule B consisted of 3 mg/kg fluconazole twice a week.
The 41 infants randomized to dosing schedule A and the 40 on dosing schedule B were similar in mean body weight (691g vs. 704 g), gestational age (25 weeks vs. 26 weeks), and risk factors for fungal infection, said Dr. Kaufman of the university's department of pediatrics. Two patients in each group had baseline fungal colonization.
During the 6-week treatment period, fungal colonization was documented in five schedule A patients (12%) and in four schedule B patients (10%). Invasive fungal infection occurred in two schedule A patients (5%) and in one schedule B patient (3%).
All these infections cleared with line removal and amphotericin treatment. All fungal isolates remained sensitive to fluconazole, and no adverse side effects were noted.
Dr. Kaufman said he and his associates would like to conduct a larger, multisite, randomized trial of 1,000-1,500 infants within the next year or 2 to confirm the findings.
“A multicenter study would better confirm the efficacy as well as further evaluate side effects and resistance,” he said. “It might also be able to show if prophylaxis would decrease mortality. Since up to 40% of extremely preterm infants who develop fungal bloodstream infections die, prevention should improve survival.”
If one assumes that each dose of fluconazole costs $50, he added, the cost difference between schedule A dosing and schedule B dosing is significant ($1,600 vs. $600, respectively).
The study was supported by a grant from Pfizer Inc., which markets fluconazole under the brand name Diflucan.
The meeting was sponsored by the American Pediatric Society, the Society for Pediatric Research, and the Ambulatory Pediatric Association.