Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data

Jessica E. Ericson, David A. Kaufman, Stephen D. Kicklighter, Jatinder Bhatia, Daniela Testoni, Jamie Gao, P. Brian Smith, Kristi O. Prather, Daniel K. Benjamin, Katherine Y. Berezny, Edmund Capparelli, Michael Cohen-Wolkowiez, Gregory L. Kearns, Matthew Laughon, Ian M. Paul, Michael J. Smith, John Van Den Anker, Kelly Wade, Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)604-610
Number of pages7
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume63
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Fluconazole
Candidiasis
Invasive Candidiasis
Premature Infants
Meta-Analysis
Placebos
Candida
Confidence Intervals
Very Low Birth Weight Infant
Sepsis
Randomized Controlled Trials
Odds Ratio
Research Personnel
Safety
Incidence

Keywords

  • candidiasis
  • fluconazole
  • meta-analysis
  • premature infants

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Ericson, J. E., Kaufman, D. A., Kicklighter, S. D., Bhatia, J., Testoni, D., Gao, J., ... Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea (2016). Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 63(5), 604-610. https://doi.org/10.1093/cid/ciw363

Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants : A Meta-analysis Using Patient-level Data. / Ericson, Jessica E.; Kaufman, David A.; Kicklighter, Stephen D.; Bhatia, Jatinder; Testoni, Daniela; Gao, Jamie; Smith, P. Brian; Prather, Kristi O.; Benjamin, Daniel K.; Berezny, Katherine Y.; Capparelli, Edmund; Cohen-Wolkowiez, Michael; Kearns, Gregory L.; Laughon, Matthew; Paul, Ian M.; Smith, Michael J.; Van Den Anker, John; Wade, Kelly; Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea.

In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 63, No. 5, 01.09.2016, p. 604-610.

Research output: Contribution to journalArticle

Ericson, JE, Kaufman, DA, Kicklighter, SD, Bhatia, J, Testoni, D, Gao, J, Smith, PB, Prather, KO, Benjamin, DK, Berezny, KY, Capparelli, E, Cohen-Wolkowiez, M, Kearns, GL, Laughon, M, Paul, IM, Smith, MJ, Van Den Anker, J, Wade, K & Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea 2016, 'Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level Data', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 63, no. 5, pp. 604-610. https://doi.org/10.1093/cid/ciw363
Ericson, Jessica E. ; Kaufman, David A. ; Kicklighter, Stephen D. ; Bhatia, Jatinder ; Testoni, Daniela ; Gao, Jamie ; Smith, P. Brian ; Prather, Kristi O. ; Benjamin, Daniel K. ; Berezny, Katherine Y. ; Capparelli, Edmund ; Cohen-Wolkowiez, Michael ; Kearns, Gregory L. ; Laughon, Matthew ; Paul, Ian M. ; Smith, Michael J. ; Van Den Anker, John ; Wade, Kelly ; Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea. / Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants : A Meta-analysis Using Patient-level Data. In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2016 ; Vol. 63, No. 5. pp. 604-610.
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abstract = "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.",
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T1 - Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants

T2 - A Meta-analysis Using Patient-level Data

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AU - Kaufman, David A.

AU - Kicklighter, Stephen D.

AU - Bhatia, Jatinder

AU - Testoni, Daniela

AU - Gao, Jamie

AU - Smith, P. Brian

AU - Prather, Kristi O.

AU - Benjamin, Daniel K.

AU - Berezny, Katherine Y.

AU - Capparelli, Edmund

AU - Cohen-Wolkowiez, Michael

AU - Kearns, Gregory L.

AU - Laughon, Matthew

AU - Paul, Ian M.

AU - Smith, Michael J.

AU - Van Den Anker, John

AU - Wade, Kelly

AU - Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act-Pediatric Trials Network Steering Committeea

N1 - © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

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