Pharmacokinetic/Pharmacodynamic Dosage Individualization of Suppressive Beta-Lactam Therapy Administered by Subcutaneous Route in Patients With Prosthetic Joint Infection

Frontiers in Medicine

Cécile Pouderoux¹  Evelyne Braun¹  Florent Valour²  Tristan Ferry²  Anne Conrad²  Sylvain Goutelle³  Sabine Cohen⁴  Marie-Claude Gagnieu⁴  Frédéric Laurent⁵  Jérôme Guitton⁶ 

[1] Centre interrégional de référence pour la prise en charge des infections ostéo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Service des maladies infectieuses et tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Centre interrégional de référence pour la prise en charge des infections ostéo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Service des maladies infectieuses et tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;CIRI—Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France;Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France;Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France;Univ Lyon, Université Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France;Centre interrégional de référence pour la prise en charge des infections ostéo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, UM Pharmacologie—Toxicologie, Lyon, France;Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France;Centre interrégional de référence pour la prise en charge des infections ostéo-articulaires complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;CIRI—Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France;Institut des Agents Infectieux, Laboratoire de bactériologie, Centre National de référence des staphylocoques, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Univ Lyon, Université Lyon 1, ISPB, Faculté de Pharmacie de Lyon, Lyon, France;Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, UM Pharmacologie—Toxicologie, Lyon, France;

关键词: prosthetic-joint infection;    antimicrobial therapy;    pharmacodynamics;    pharmacokinetics;    beta-lactam;    subcutaneous administration;   

DOI  :  10.3389/fmed.2021.583086

来源: Frontiers

【 摘 要 】

Suppressive parenteral antibiotic therapy with beta-lactams may be necessary in patients with Gram-negative bone and joint infection (BJI). Subcutaneous drug administration can facilitate this therapy in outpatient setting, but there is limited information about this practice. We have developed an original approach for drug dosing in this context, based on therapeutic drug monitoring (TDM) and pharmacokinetic/pharmacodynamic (PK/PD) principles. The objective of this study was to describe our approach and its first results in a case series. We analyzed data from patients who received suppressive antibiotic therapy by subcutaneous (SC) route with beta-lactams as salvage therapy for prosthetic joint infection (PJI) and had TDM with PK/PD-based dose adjustment. Ten patients (six women and four men with a mean age of 77 years) were included from January 2017 to May 2020. The drugs administered by SC route were ceftazidime (n = 4), ertapenem (n = 4), and ceftriaxone (n = 2). In each patient, PK/PD-guided dosage individualization was performed based on TDM and minimum inhibitory concentration (MIC) measurements. The dose interval could be prolonged from twice daily to thrice weekly in some patients, while preserving the achievement of PK/PD targets. The infection was totally controlled by the strategy in nine out the 10 patients during a median follow-up of 1,035 days (~3 years). No patient acquired carbapenem-resistant Gram-negative bacteria during the follow-up. One patient presented treatment failure with acquired drug resistance under therapy, which could be explained by late MIC determination and insufficient exposure, retrospectively. To conclude, our innovative approach, based on model-based TDM, MIC determination, and individualized PK/PD goals, facilitates, and optimizes suppressive outpatient beta-lactam therapy administered by SC route for PJI. These encouraging results advocate for larger clinical evaluation.

【 授权许可】

CC BY