Pharmacokinetics of cefuroxime in synovial fluid [PublishAheadOfPrint]

Objectives: Cefuroxime is frequently used as preoperative antibiotic prophylaxis and may be used for 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.

Patients and Methods: Ten patients who underwent elective knee arthroscopy were included in this study. Patients were treated with a single dose of 1500 mg cefuroxime intravenously and subsequently concentrations were measured in plasma, interstitial fluid of muscle tissue and synovial fluid by using microdialysis. Pharmacokinetics / Pharmacodynamic calculations to predict bacterial killing were performed using epidemiologically defined MIC₉₀ of clinical isolates andCLSI breakpoints.

Results: Cefuroxime penetrated excellently into muscle tissue (AUC_muscle:AUC_{free plasma}: 1.79) and synovial fluid (AUC_synovia:AUC_{free plasma}: 1.94). Cefuroxime concentration was beyond the MIC₉₀ of S. aureus and S. epidermidis strains (≤ 2 mg/L) over the complete dosing interval (fT>MIC). CLSI defines staphylococci with MIC ≤ 8 mg/L as susceptible to cefuroxime. For staphylococci with MIC ≤ 8 mg/L, the fT>MIC of cefuroxime in plasma was 52.5% while in muscle tissue and synovial fluid fT>MIC was 93.6% and 96.3%, respectively.

Conclusion: Cefuroxime may be used to treat septic arthritis caused by susceptible bacterial strains (MIC ≤ 8 mg/L). The activity of cefuroxime in septic arthritis might be underestimated when relying exclusively on plasma concentrations.

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