Fluconazole prophylaxis in extremely low birth weight neonates reduces invasive candidiasis mortality rates without emergence of fluconazole-resistant Candida species.
OBJECTIVE
We evaluated the impact of fluconazole prophylaxis for extremely low birth weight infants on invasive candidiasis incidence, invasive candidiasis-related mortality rates, and fluconazole susceptibility of Candida isolates.


METHODS
Extremely low birth weight infants <5 days of age, except those with liver dysfunction, were eligible for fluconazole prophylaxis. NICU infants (all birth weights) with invasive candidiasis between April 2002 and March 2006 were compared with those with invasive candidiasis before fluconazole prophylaxis (2000-2001).


RESULTS
Twenty-two infants had invasive candidiasis (all candidemia) during fluconazole prophylaxis; before fluconazole prophylaxis, there were 19 cases (candidemia: 17 cases; meningitis: 2 cases). Invasive candidiasis incidence in NICU infants decreased from 0.6% (19 of 3012 infants) before fluconazole prophylaxis to 0.3% (22 of 6393 infants) in 2002-2006 and that in extremely low birth weight infants decreased 3.6-fold. No Candida-attributable deaths occurred during 2002-2006 fluconazole prophylaxis, compared with 4 (21%) before fluconazole prophylaxis. The onset of invasive candidiasis was later during 2002-2006 (23.5 vs 12 days), but risk factors were similar. The invasive candidiasis species distribution remained stable. Of 409 infants who received fluconazole prophylaxis, 119 (29%) received 42 days. Shorter fluconazole prophylaxis duration was related to intravenous access no longer being necessary in 242 cases (59%), noninvasive candidiasis-related death in 29 (7%), hospital transfer in 8 (2%), invasive candidiasis diagnosis in 8 (2%), and transient increase in serum transaminase levels in 4 (1%). One hundred twenty-seven infants (31%) who received fluconazole prophylaxis developed cholestasis during hospitalization, two thirds of whom had other predisposing conditions. On multivariate logistic regression necrotizing enterocolitis and increasing days of total parenteral nutrition, but not increasing number of doses on days of fluconazole, were significantly associated with the development of cholestasis.


CONCLUSIONS
During 4 years of fluconazole prophylaxis, the incidence of invasive candidiasis and invasive candidiasis-associated mortality rates in extremely low birth weight infants were reduced significantly, without the emergence of fluconazole-resistant Candida species.
Healy
C Mary
CM
Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, One Baylor Plaza, Room 302A, MS BCM 320, Houston, TX 77030, USA. chealy@bcm.edu
Campbell
Judith R
JR
Zaccaria
Elena
E
Baker
Carol J
CJ
D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000008:administration & dosage; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D016015:Logistic Models; D008297:Male; D008826:Microbial Sensitivity Tests; D015999:Multivariate Analysis; D009181:Mycoses / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate
D000935:Antifungal Agents; D015725:Fluconazole