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Zeller V, Magreault S, Heym B, et al. Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study. Clin Microbiol Infect. 2021;27(12):1857.e1-1857.e7doi: 10.1016/j.cmi.2021.04.017.
Zeller, V., Magreault, S., Heym, B., Salmon, D., Kitzis, M. D., Billaud, E., Marmor, S., Jannot, A. S., Salomon, L., & Jullien, V. (2021). Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 27(12), 1857.e1-1857.e7. https://doi.org/10.1016/j.cmi.2021.04.017
Zeller, Valérie, et al. "Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study." Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases vol. 27,12 (2021): 1857.e1-1857.e7. doi: https://doi.org/10.1016/j.cmi.2021.04.017
Zeller V, Magreault S, Heym B, Salmon D, Kitzis MD, Billaud E, Marmor S, Jannot AS, Salomon L, Jullien V. Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study. Clin Microbiol Infect. 2021 Dec;27(12):1857.e1-1857.e7. doi: 10.1016/j.cmi.2021.04.017. Epub 2021 Apr 26. PMID: 33915288.
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Clin Microbiol Infect. 2021 Dec;27(12):1857.e1-1857.e7. doi: 10.1016/j.cmi.2021.04.017. Epub 2021 Apr 26.

Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

Valérie Zeller, Sophie Magreault, Beate Heym, Dominique Salmon, Marie-Dominique Kitzis, Eliane Billaud, Simon Marmor, Anne-Sophie Jannot, Laurence Salomon, Vincent Jullien

Affiliations

  1. Centre de Référence des Infections Ostéo-Articulaires Complexes (CRIOAC), Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France; Service de Médecine Interne et Infectiologie, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France. Electronic address: [email protected].
  2. Unité Fonctionnelle de Pharmacologie, Groupe Hospitalier Paris-Seine-Saint-Denis, Bondy, France; IAME UMR 1137, Inserm and Paris Diderot University, Team Biostatistic Modelling, Clinical Investigation and Pharmacometrics in Infectious Diseases, Paris, France.
  3. Centre de Référence des Infections Ostéo-Articulaires Complexes (CRIOAC), Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
  4. Service de Médecine Interne, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
  5. Service de Microbiologie, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
  6. Service de Pharmacologie DMU BioPhyGen, Hôpital Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
  7. Service d'Informatique Médicale, Biostatistiques et Santé Publique, Hôpital Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
  8. Service de Recherche Clinique, Hôpital Fondation Adolphe de Rothschild, Paris, France.
  9. Unité Fonctionnelle de Pharmacologie, Groupe Hospitalier Paris-Seine-Saint-Denis, Bondy, France.

PMID: 33915288 DOI: 10.1016/j.cmi.2021.04.017

Abstract

OBJECTIVES: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration.

METHODS: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route.

RESULTS: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC

CONCLUSION: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Keywords: Bone and joint infections; Clindamycin; Drug interaction; Oral and IV routes; Pharmacokinetics; Rifampicin

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