RESUMO
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 0.76â±â0.34 (synovial fluid) and 0.98â±â0.62 (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 86.8â±â47.0, 43.4â±â23.5 and 21.7â±â11.8, 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 >â50 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.
Assuntos
Antibacterianos/farmacocinética , Linezolida/farmacocinética , Músculos/química , Líquido Sinovial/química , Administração Intravenosa , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/sangue , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/microbiologia , Artroscopia , Procedimentos Cirúrgicos Eletivos , Feminino , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Articulação do Joelho/cirurgia , Linezolida/administração & dosagem , Linezolida/efeitos adversos , Linezolida/sangue , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-IdadeRESUMO
Cefuroxime is frequently used as preoperative antibiotic prophylaxis and may be used for the treatment of septic arthritis. A prerequisite for successful treatment of septic arthritis is the ability of an antibiotic agent to penetrate into the target site. Therefore, the concentration of cefuroxime in synovial fluid was evaluated. Ten patients who underwent elective knee arthroscopy were included in this study. Patients were treated with a single dose of 1,500 mg cefuroxime intravenously, and subsequently, the concentrations in plasma, the interstitial fluid of muscle tissue, and synovial fluid were measured by using microdialysis. Pharmacokinetic/pharmacodynamic calculations to predict bacterial killing were performed using the epidemiologically defined MIC90 for clinical isolates and CLSI breakpoints. Cefuroxime penetrated excellently into muscle tissue (ratio of the area under the concentration-time curve [AUC] for muscle tissue/AUC for free plasma, 1.79) and synovial fluid (ratio of the AUC for synovial fluid/AUC for free plasma, 1.94). The cefuroxime concentration was greater than the MIC90 for Staphylococcus aureus and S. epidermidis strains (≤2 mg/liter) over the complete dosing interval (the percentage of the dosing interval during which the free cefuroxime concentration exceeded the MIC for the pathogen [fTMIC]). CLSI defines staphylococci with MICs of ≤8 mg/liter to be susceptible to cefuroxime. For staphylococci with MICs of ≤8 mg/liter, the fTMIC in plasma was 52.5%, while the fTMIC in muscle tissue and synovial fluid was 93.6% and 96.3%, respectively. Cefuroxime may be used to treat septic arthritis caused by susceptible bacterial strains (MIC ≤ 8 mg/liter). The activity of cefuroxime in septic arthritis might be underestimated when relying exclusively on plasma concentrations.