Ciprofloxacin population pharmacokinetics during long-term treatment of osteoarticular infections

作者：Noël Zahr, Saı̈k Urien, Alexandra Aubry, Charlotte Chauvin, Emmanuelle Comets, B Llopis, Nadine Tissot, Gaëlle Noé, É. Fourniols, Stéphane Jauréguiberry, Alexandre Bleibtreu, Christian Funck‐Brentano, Nicolas Barrut, Isabelle Bonnet, Ruxandra Câlin, Éric Caumes, Frédéric Clarençon, G Daas, Bruno Fautrel, Anne Fustier, Frédérique Gandjbakhch, Élie Haddad, F. Khiami, Jean Yves Lazennec, Maxime Marchant, Guillaume Mercy, Carole Metz, Mihaela Miu, Stéphane Mitrovic, Gentiane Monsel, Quentin Monzani, Vanessa Reubrecht, J. Robert · 发表于：Journal of Antimicrobial Chemotherapy · 年份：2021 · DOI：10.1093/jac/dkab275 · 被引用次数：11 · 研究领域：Orthopedic Infections and Treatments、Antibiotics Pharmacokinetics and Efficacy、Infectious Diseases and Tuberculosis

BACKGROUND: Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population. OBJECTIVES: To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing. METHODS: A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2. RESULTS: A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients' fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased b...