Published online December 1, 2005
PEDIATRICS Vol. 117 No. 1 January 2006, pp. e22-e32 (doi:10.1542/peds.2004-2227)

This Article Full Text Full Text (PDF) Submit a response View responses Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Manzoni, P. Articles by Gomirato, G. Search for Related Content PubMed PubMed Citation Articles by Manzoni, P. Articles by Gomirato, G. Related Collections Infectious Disease & Immunity Social Bookmarking                         What's this?

ARTICLE

Prophylactic Fluconazole Is Effective in Preventing Fungal Colonization and Fungal Systemic Infections in Preterm Neonates: A Single-Center, 6-Year, Retrospective Cohort Study

Paolo Manzoni, MD^a, Riccardo Arisio, MD^b, Michael Mostert, MD^c, MariaLisa Leonessa, MD^a, Daniele Farina, MD^a, Maria Agnese Latino, MD^d and Giovanna Gomirato, MD^a

^a Neonatology and Hospital NICU
^b Departments of Pathology
^c Pediatric Sciences
^d Clinical Pathology and Microbiology, Azienda Ospedaliera Regina Margherita-S. Anna, Torino, Italy

OBJECTIVE. Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis.

METHODS. This retrospective study consisted of 465 neonates who weighed <1500 g at birth and were admitted to our NICU in the period 1998–2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates <1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were <1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth.

RESULTS. Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273–0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113–0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159–0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039–0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred.

CONCLUSIONS. Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.

---

Key Words: fluconazole • very low birth weight infant • Candida • infection • colonization • prophylaxis

Abbreviations: SFI—systemic fungal infection • LOS—late-onset sepsis • VLBW—very low birth weight • ELBW—extremely low birth weight • NE-VLBW—very low birth weight neonates, excluding ELBW neonates • LAmB—liposomal amphotericin B • dol, day of life • RR—relative risk • CI—confidence interval • MIC—minimal inhibitory concentration

---

Accepted Jul 7, 2005.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. M. Healy Fungal Prophylaxis in the Neonatal Intensive Care Unit NeoReviews, December 1, 2008; 9(12): e562 - e570. [Abstract] [Full Text] [PDF]

				F. H. Morriss Jr Adverse Medical Events in the NICU: Epidemiology and Prevention NeoReviews, January 1, 2008; 9(1): e8 - e23. [Abstract] [Full Text] [PDF]

				B. A McCrossan, E. McHenry, F. O'Neill, G. Ong, and D. G Sweet Selective fluconazole prophylaxis in high-risk babies to reduce invasive fungal infection Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2007; 92(6): F454 - F458. [Abstract] [Full Text] [PDF]

				P. Manzoni, I. Stolfi, L. Pugni, L. Decembrino, C. Magnani, G. Vetrano, E. Tridapalli, G. Corona, C. Giovannozzi, D. Farina, et al. A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates N. Engl. J. Med., June 14, 2007; 356(24): 2483 - 2495. [Abstract] [Full Text] [PDF]

eLetters:

Read all eLetters

Fluconazole antifungal prophylaxis - why is it necessary?

David W Cartwright

Pediatrics Online, 11 Jan 2006 [Full text]