Kim C M van der Elst1, Marieke Pereboom1, Edwin R van den Heuvel2, Jos G W Kosterink3, Elisabeth H Schölvinck4, Jan-Willem C Alffenaar1. 1. Department of Clinical Pharmacy and Pharmacology. 2. Department of Epidemiology. 3. Department of Clinical Pharmacy and Pharmacology Department of Pharmacy, Section of Pharmacotherapy and Pharmaceutical Care. 4. Department of Pediatrics (Infection/Immunology), University Medical Center Groningen, University of Groningen, The Netherlands.
Abstract
BACKGROUND: 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.
BACKGROUND: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 cancerpatients 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.
Authors: J M Boonstra; A G Märtson; I Sandaradura; J G W Kosterink; T S van der Werf; D J E Marriott; J G Zijlstra; D J Touw; J W C Alffenaar Journal: Antimicrob Agents Chemother Date: 2021-02-17 Impact factor: 5.191
Authors: Kim C M van der Elst; Manouche van Alst; Marjolijn N Lub-de Hooge; Kai van Hateren; Jos G W Kosterink; Jan-Willem C Alffenaar; Elisabeth H Schölvinck Journal: Antimicrob Agents Chemother Date: 2014-09-02 Impact factor: 5.191
Authors: Melissa D Johnson; Russell E Lewis; Elizabeth S Dodds Ashley; Luis Ostrosky-Zeichner; Theoklis Zaoutis; George R Thompson; David R Andes; Thomas J Walsh; Peter G Pappas; Oliver A Cornely; John R Perfect; Dimitrios P Kontoyiannis Journal: J Infect Dis Date: 2020-08-05 Impact factor: 5.226