FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 356:2483-2495 June 14, 2007 Number 24 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Sobel, J. D. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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] ).

Source Information

From Sant'Anna Hospital, Turin (P.M., C.G., D.F., G.G.); Policlinico Umberto I, Rome (I.S., R.P.); Mangiagalli Hospital IRCCS, University of Milan, Milan (L.P., F. Mosca); San Matteo Hospital, Pavia (L.D., M.S.); Arcispedale, Reggio Emilia (C.M.); Fatebenefratelli Hospital, Benevento (G.V.); University of Bologna, Bologna (E.T.); University of Messina, Messina (G.C.); and University of Turin, Turin (R.A., M. Maule, F. Merletti, M. Mostert) — all in Italy.

Address reprint requests to Dr. Manzoni at the Neonatology and Hospital Neonatal Intensive Care Unit, Sant'Anna Hospital, Corso Spezia 60, 10126 Turin, Italy, or at paolomanzoni{at}hotmail.com.

Full Text of this Article

Related Letters:

Prophylactic Fluconazole in Preterm Neonates
Vain N. E., Vazquez L. N., Procianoy R. S., Silveira R. C., Manzoni P., Mostert M., Farina D.
Extract | Full Text | PDF  
N Engl J Med 2007; 357:1348-1349, Sep 27, 2007. Correspondence

This article has been cited by other articles:

• Howell, A, Isaacs, D, Halliday, R, Infections, T. A. S. G. f. N. (2009). Oral nystatin prophylaxis and neonatal fungal infections. Arch. Dis. Child. Fetal Neonatal Ed. 94: F429-F433 [Abstract] [Full Text]  
• Pfaller, M. A., Messer, S. A., Hollis, R. J., Boyken, L., Tendolkar, S., Kroeger, J., Diekema, D. J. (2009). Variation in Susceptibility of Bloodstream Isolates of Candida glabrata to Fluconazole According to Patient Age and Geographic Location in the United States in 2001 to 2007. J. Clin. Microbiol. 47: 3185-3190 [Abstract] [Full Text]  
• Laer, S., Barrett, J. S., Meibohm, B. (2009). The In Silico Child: Using Simulation to Guide Pediatric Drug Development and Manage Pediatric Pharmacotherapy. J Clin Pharmacol 49: 889-904 [Abstract] [Full Text]  
• Ganesan, K, Harigopal, S, Neal, T, Yoxall, C W (2009). Prophylactic oral nystatin for preterm babies under 33 weeks' gestation decreases fungal colonisation and invasive fungaemia. Arch. Dis. Child. Fetal Neonatal Ed. 94: F275-F278 [Abstract] [Full Text]  
• Vendettuoli, V., Vento, G., Tirone, C., Posteraro, B., Romagnoli, C. (2009). Antifungal Prophylaxis: Identification of Preterm Neonates at Highest Risk for Invasive Fungal Infection. Pediatrics 123: e368-e369 [Full Text]  
• Brecht, M, Clerihew, L, McGuire, W (2009). Prevention and treatment of invasive fungal infection in very low birthweight infants. Arch. Dis. Child. Fetal Neonatal Ed. 94: F65-F69 [Abstract] [Full Text]  
• Healy, C. M. (2008). Fungal Prophylaxis in the Neonatal Intensive Care Unit. NeoReviews 9: e562-e570 [Abstract] [Full Text]  
• Kaufman, D. (2008). Fluconazole Prophylaxis Decreases the Combined Outcome of Invasive Candida Infections or Mortality in Preterm Infants. Pediatrics 122: 1158-1159 [Full Text]  
• Clerihew, L, Austin, N, McGuire, W (2008). Systemic antifungal prophylaxis for very low birthweight infants: a systematic review. Arch. Dis. Child. Fetal Neonatal Ed. 93: F198-F200 [Abstract] [Full Text]  
• Healy, C. M., Campbell, J. R., Zaccaria, E., Baker, C. J. (2008). Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species. Pediatrics 121: 703-710 [Abstract] [Full Text]  
• Vain, N. E., Vazquez, L. N., Procianoy, R. S., Silveira, R. C., Manzoni, P., Mostert, M., Farina, D. (2007). Prophylactic Fluconazole in Preterm Neonates. NEJM 357: 1348-1349 [Full Text]  
• Sobel, J. D., Revankar, S. G. (2007). Echinocandins -- First-Choice or First-Line Therapy for Invasive Candidiasis?. NEJM 356: 2525-2526 [Full Text]  
• (2007). Fluconazole to Prevent Neonatal Candidiasis. JWatch Infect. Diseases 2007: 2-2 [Full Text]