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More on Fluconazole Prophylaxis
Manzoni P, M.D, Stolfi I, Pugni L, et al. A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates. New Engl J Med (June 14, 2007); 356:2483-2495. Full Text | PDF
Background. Invasive Candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates.
Methods. During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing.
Results. Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant Candida species was observed, but the study did not have substantial power to detect such an effect.
Conclusions. Prophylactic fluconazole reduces the incidence of colonization and invasive Candida infection in neonates weighing less than 1500 g at birth. The benefit of treating Candida colonization is unclear.
Comments. This multi-center RCT confirms the efficacy of
fluconazole prophylaxis in preventing fungal colonization and infection in
very premature infants. There were no adverse effects noted in the
fluconazole groups, and no emergence of resistant Candida was observed.
Please note that the incidence of invasive fungal infections was 13.2% in the
control group. This rate is much higher than the mean rate of invasive fungal
infections in VLBW infants reported to the Vermont Oxford network (about 3%).
The primary ways to prevent fungal sepsis in preterm infants remain the same:
1) judicious use of broad-spectrum antibiotics; and 2) meticulous hand
hygiene. If your NICU has a very high fungal sepsis rate despite those
measures, then fluconazole prophylaxis should be considered. For more
information on this topic, see
2-002,
6-034, and
7-037. ABK
Date: 02 Jul 2007
Time: 21:48:01
We use nystatin topically and p.o. daily on all infants with PICC's, and have
had essentially zero invasive fungal infection since starting this protocol!
That's probably a lot safer than fluconazole.
UserName: Paul Hinkes MD
Institution: Providence St. Joseph Medical Center
telephone: 818-847-6332
email: preemys@msn.com
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