Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations

Eline W Muilwijk; Bart G J Dekkers; Stefanie S V Henriet; Paul E Verweij; Bregje Witjes; Astrid M L Oude Lashof; Geert H Groeneveld; Johannes van der Hoeven; Jan Willem C Alffenaar; Frans G M Russel; Frank van de Veerdonk; Roger J M Brüggemann

doi:10.1128/AAC.00915-17

Flucloxacillin Results in Suboptimal Plasma Voriconazole Concentrations

Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00915-17. doi: 10.1128/AAC.00915-17. Print 2017 Sep.

Authors

Eline W Muilwijk^{1

2}, Bart G J Dekkers³, Stefanie S V Henriet^{2

4}, Paul E Verweij^{2

5}, Bregje Witjes⁶, Astrid M L Oude Lashof⁷, Geert H Groeneveld⁸, Johannes van der Hoeven⁹, Jan Willem C Alffenaar³, Frans G M Russel¹⁰, Frank van de Veerdonk^{2

11}, Roger J M Brüggemann^{1

2}

Affiliations

¹ Department of Pharmacy, Radboud university medical center, Nijmegen, The Netherlands eline.muilwijk@radboudumc.nl roger.bruggemann@radboudumc.nl.
² Center of Expertise in Mycology Radboudumc/CWZ and Radboud Institute of Health Science, Nijmegen, The Netherlands.
³ University of Groningen, University Medical Centre Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
⁴ Department of Pediatric Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands.
⁵ Department of Medical Microbiology, Radboud university medical center, Nijmegen, The Netherlands.
⁶ Department of Clinical Pharmacology and Pharmacy, VU University Medical Centre, Amsterdam, The Netherlands.
⁷ School for Public Health and Primary Care (Caphri), Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands.
⁸ Department of Internal Medicine and Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Department of Intensive Care, Radboud university medical center, Nijmegen, The Netherlands.
¹⁰ Department of Pharmacology and Toxicology, Radboud university medical center, Nijmegen, The Netherlands.
¹¹ Department of Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands.

Abstract

Combining voriconazole and flucloxacillin is indicated in patient cohorts experiencing both invasive aspergillosis and Gram-positive infections (e.g., patients with chronic granulomatous disease or postinfluenza pulmonary aspergillosis). We report a highly relevant interaction between voriconazole and flucloxacillin, resulting in subtherapeutic plasma voriconazole concentrations in more than 50% of patients, that poses a severe threat if not managed properly.

Keywords: aspergillosis; drug interactions; exposure; influenza; pharmacokinetics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antifungal Agents / blood*
Antifungal Agents / therapeutic use*
Aspergillus / drug effects
Child
Child, Preschool
Drug Interactions
Female
Floxacillin / therapeutic use*
Granulomatous Disease, Chronic / blood
Granulomatous Disease, Chronic / drug therapy
Granulomatous Disease, Chronic / microbiology
Humans
Invasive Fungal Infections / blood
Invasive Fungal Infections / drug therapy
Male
Middle Aged
Pulmonary Aspergillosis / blood
Pulmonary Aspergillosis / drug therapy
Voriconazole / blood*
Voriconazole / therapeutic use*
Young Adult

Substances

Antifungal Agents
Floxacillin
Voriconazole