R Schwameis1, S Syré2, K Sarahrudi2, A Appelt3, D Marhofer4, D Burau3, C Kloft3, M Zeitlinger1. 1. Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. 2. Department of Trauma Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. 3. Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany. 4. Department of Anaesthesia, Intensive Care Medicine, and Pain Therapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Abstract
Objectives: Penetration of antibiotics into synovial fluid is crucial to combat septic arthritis efficiently. Since linezolid may be used for treatment of septic arthritis when methicillin-resistant bacterial strains are suspected, we investigated its target-site concentrations in synovial fluid. Patients and methods: Ten patients undergoing elective knee arthroscopy were included in this study. Subjects received a single dose of 600 mg of linezolid intravenously and linezolid concentrations were measured in plasma and by using microdialysis in muscle tissue and synovial fluid. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing ability were performed using CLSI breakpoints and MIC90 for clinical isolates. Results: All 10 subjects tolerated linezolid well. As indicated by AUCtissue/AUCfree plasma ratios of 0.76 ± 0.34 (synovial fluid) and 0.98 ± 0.62 (muscle tissue) linezolid penetrated well into the knee gap and tissue. In synovial fluid AUC0-24/MIC ratios for bacteria with an MIC of 1, 2 and 4 mg/L were 86.8 ± 47.0, 43.4 ± 23.5 and 21.7 ± 11.8, respectively. Conclusions: Linezolid may be used to treat septic arthritis caused by bacterial strains with an MIC ≤1 mg/L. Assuming a pharmacokinetic/pharmacodynamic target of > 50 for AUC0-24/MIC, when treating strains with an MIC >1 mg/L treatment surveillance is warranted. However, pharmacokinetic/pharmacodynamic targets for tissue are poorly understood and clinical data are needed to verify our assumptions.
Objectives: Penetration of antibiotics into synovial fluid is crucial to combat septic arthritis efficiently. Since linezolid may be used for treatment of septic arthritis when methicillin-resistant bacterial strains are suspected, we investigated its target-site concentrations in synovial fluid. Patients and methods: Ten patients undergoing elective knee arthroscopy were included in this study. Subjects received a single dose of 600 mg of linezolid intravenously and linezolid concentrations were measured in plasma and by using microdialysis in muscle tissue and synovial fluid. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing ability were performed using CLSI breakpoints and MIC90 for clinical isolates. Results: All 10 subjects tolerated linezolid well. As indicated by AUCtissue/AUCfree plasma ratios of 0.76 ± 0.34 (synovial fluid) and 0.98 ± 0.62 (muscle tissue) linezolid penetrated well into the knee gap and tissue. In synovial fluid AUC0-24/MIC ratios for bacteria with an MIC of 1, 2 and 4 mg/L were 86.8 ± 47.0, 43.4 ± 23.5 and 21.7 ± 11.8, respectively. Conclusions: Linezolid may be used to treat septic arthritis caused by bacterial strains with an MIC ≤1 mg/L. Assuming a pharmacokinetic/pharmacodynamic target of > 50 for AUC0-24/MIC, when treating strains with an MIC >1 mg/L treatment surveillance is warranted. However, pharmacokinetic/pharmacodynamic targets for tissue are poorly understood and clinical data are needed to verify our assumptions.
Authors: Philipp Simon; David Busse; David Petroff; Christoph Dorn; Lisa Ehmann; Sophie Hochstädt; Felix Girrbach; Arne Dietrich; Markus Zeitlinger; Frieder Kees; Charlotte Kloft; Hermann Wrigge Journal: J Clin Med Date: 2020-04-09 Impact factor: 4.241