title: A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.
abstract: 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. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).
authors.affiliation: Neonatology and Hospital Neonatal Intensive Care Unit, Sant'Anna Hospital, Turin, Italy. paolomanzoni@hotmail.com
authors.forename: Paolo
authors.initials: P
authors.lastname: Manzoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Stolfi
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pugni
authors.forename: Lidia
authors.initials: L
authors.lastname: Decembrino
authors.forename: Cristiana
authors.initials: C
authors.lastname: Magnani
authors.forename: Gennaro
authors.initials: G
authors.lastname: Vetrano
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tridapalli
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Corona
authors.forename: Chiara
authors.initials: C
authors.lastname: Giovannozzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Farina
authors.forename: Riccardo
authors.initials: R
authors.lastname: Arisio
authors.forename: Franco
authors.initials: F
authors.lastname: Merletti
authors.forename: Milena
authors.initials: M
authors.lastname: Maule
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedicino
authors.forename: Mauro
authors.initials: M
authors.lastname: Stronati
authors.forename: Michael
authors.initials: M
authors.lastname: Mostert
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gomirato
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000302:isolation & purification; D002177:Candidiasis / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D002779:Cholestasis / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D008297:Male; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole