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Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children.

AbstractBACKGROUND:
Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended.
METHODS:
We conducted a retrospective study of critically ill children treated with fluconazole from January 2007 to October 2013 and for whom fluconazole concentrations were available. We collected demographic, clinical, and treatment data through review of the medical records and determined the correlation of clinical variables with the fluconazole concentration. Additionally, we assessed the relation between the fluconazole concentration and the time to culture conversion in patients with proven invasive candidiasis.
RESULTS:
In total, 99 pediatric patients met the inclusion criteria. The fluconazole concentration was considered subtherapeutic in 40% of the patients. Multiple linear regression analysis showed a significant, independent, and positive association of the fluconazole trough concentration with the fluconazole dose (P <.001), weight (P = .009), and the serum urea concentration (P = .003), and a significant, independent, and negative association with age (P = .004) and cancer as an underlying condition (P = .003). A higher fluconazole concentration was associated with a shorter time to culture conversion (hazard ratio = 1.076 [95% confidence interval, 1.017-1.138]; P = .011).
CONCLUSIONS:
The fluconazole concentration is not sufficient in pediatric cancer patients with the currently recommended dose regimen, and a higher fluconazole dose is required to achieve adequate drug exposure. Therapeutic drug monitoring of fluconazole can be a valuable tool to detect possible underexposure in critically ill children.
AuthorsKim C M van der Elst, Marieke Pereboom, Edwin R van den Heuvel, Jos G W Kosterink, Elisabeth H Schölvinck, Jan-Willem C Alffenaar
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 59 Issue 11 Pg. 1527-33 (Dec 01 2014) ISSN: 1537-6591 [Electronic] United States
PMID25148892 (Publication Type: Journal Article)
Copyright© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].
Chemical References
  • Antifungal Agents
  • Fluconazole
Topics
  • Adolescent
  • Antifungal Agents (administration & dosage, blood, pharmacokinetics)
  • Candidiasis (drug therapy, metabolism, pathology)
  • Child
  • Child, Preschool
  • Critical Illness
  • Drug Monitoring (methods)
  • Female
  • Fluconazole (administration & dosage, blood, pharmacokinetics)
  • Humans
  • Infant
  • Infant, Newborn
  • Linear Models
  • Male
  • Neoplasms (metabolism, microbiology)
  • Netherlands
  • Retrospective Studies

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