Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data.
BACKGROUND
Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated with a high risk of death and neurodevelopmental impairment. Prevention of IC has become a major focus in very low birth weight infants, with fluconazole increasingly used as prophylaxis.


METHODS
We identified all randomized, placebo-controlled trials evaluating fluconazole prophylaxis in premature infants conducted in the United States. We obtained patient-level data from the study investigators and performed an aggregated analysis. The occurrence of each endpoint in infants who received prophylaxis with fluconazole vs placebo was compared. Endpoints evaluated were IC or death, IC, death, Candida colonization, and fluconazole resistance among tested isolates. Safety endpoints evaluated included clinical and laboratory parameters.


RESULTS
Fluconazole prophylaxis reduced the odds of IC or death, IC, and Candida colonization during the drug exposure period compared with infants given placebo: odds ratios of 0.48 (95% confidence interval [CI], .30-.78), 0.20 (95% CI, .08-.51), and 0.28 (95% CI, .18-.41), respectively. The incidence of clinical and laboratory adverse events was similar for infants who received fluconazole compared with placebo. There was no statistically significant difference in the proportion of tested isolates that were resistant to fluconazole between the fluconazole and placebo groups.


CONCLUSIONS
Fluconazole prophylaxis is effective and safe in reducing IC and Candida colonization in premature infants, and has no impact on resistance.
Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania.
Jessica E
JE
Ericson
Department of Pediatrics, University of Virginia, Charlottesville.
David A
DA
Kaufman
Wake Medical Center, Raleigh, North Carolina.
Stephen D
SD
Kicklighter
Department of Pediatrics, Georgia Regents University, Augusta.
Jatinder
J
Bhatia
Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
Daniela
D
Testoni
Duke Clinical Research Institute.
Jamie
J
Gao
Duke Clinical Research Institute Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
P Brian
PB
Smith
Duke Clinical Research Institute.
Kristi O
KO
Prather
Duke Clinical Research Institute Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
Daniel K
DK
Benjamin
D019072:Antibiotic Prophylaxis / Q000009:adverse effects / Q000379:methods / Q000706:statistics & numerical data; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D058365:Candidiasis, Invasive / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D007234:Infant, Premature; D008297:Male; D016032:Randomized Controlled Trials as Topic; D014481:United States
D000935:Antifungal Agents; D015725:Fluconazole
fluconazole; candidiasis; meta-analysis; premature infants