Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants

Julie Autmizguine, P. Brian Smith, Kristi Prather, Catherine Bendel, Girija Natarajan, Margarita Bidegain, David A. Kaufman, David J. Burchfield, Ashley S. Ross, Paresh Pandit, Wiley A. Schell, Jamie Gao, Daniel K. Benjamin, Scott Macgilvray, Kelly Wade, Rune Toms, Neil Finer, Dan Stewart, Antonio Arrieta, Shahnaz DuaraSeetha Shankaran, Jonathan Nedrelow, Robert White, Anand Kantak, Karen Shattuck, Mohan Pammi, Kathleen Kennedy, Pablo Sanchez, Ramasubbareddy Dhanireddy, Barry Bloom, Mark Hudak, Agnes Perenyi, Natalie Neu, Echezona Ezeanolue, Roger Kim, Gratias Mundakel, Brenda Poindexter, Phillip Gordon

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objectives Extremely premature infants are at high risk of developing invasive candidiasis; fluconazole prophylaxis is safe and effective for reducing invasive candidiasis in this population but further study is needed. We sought to better understand the effect of prophylactic fluconazole on a selection of fluconazole-resistant Candida species. Methods We evaluated the susceptibility to fluconazole of Candida isolates from premature infants (<750 g birth weight) enrolled in a multicentre, randomized, placebo-controlled trial of fluconazole prophylaxis. Candida species were isolated through surveillance cultures at baseline (study day 0-7), period 1 (study day 8-28) and period 2 (study day 29-49). Fluconazole MICs were determined for all Candida isolates. Results Three hundred and sixty-one infants received fluconazole (n = 188) or placebo (n = 173). After the baseline period, Candida colonization was significantly lower in the fluconazole group compared with placebo during periods 1 (5% versus 27%; P < 0.001) and 2 (3% versus 27%; P < 0.001). After the baseline period, two infants (1%) were colonized with at least one fluconazole-resistant Candida in each group. Median fluconazole MIC was similar in both treatment groups at baseline and period 1. However, in period 2, median MIC was higher in the fluconazole group compared with placebo (1.00 versus 0.50 mg/L, P = 0.01). There was no emergence of resistance observed and no patients developed invasive candidiasis with a resistant Candida isolate. Conclusions Fluconazole prophylaxis decreased Candida albicans and € non-albicans' Candida colonization and was associated with a slightly higher fluconazole MIC for colonizing Candida isolates.

Original languageEnglish (US)
Pages (from-to)3482-3487
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number12
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Autmizguine, J., Smith, P. B., Prather, K., Bendel, C., Natarajan, G., Bidegain, M., Kaufman, D. A., Burchfield, D. J., Ross, A. S., Pandit, P., Schell, W. A., Gao, J., Benjamin, D. K., Macgilvray, S., Wade, K., Toms, R., Finer, N., Stewart, D., Arrieta, A., ... Gordon, P. (2018). Effect of fluconazole prophylaxis on Candida fluconazole susceptibility in premature infants. Journal of Antimicrobial Chemotherapy, 73(12), 3482-3487. https://doi.org/10.1093/jac/dky353