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Antimicrob Agents Chemother. 2017 Sep 22;61(10). pii: e00992-17. doi: 10.1128/AAC.00992-17. Print 2017 Oct.

Pharmacokinetics of Cefuroxime in Synovial Fluid.

Author information

1
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
2
Department of Trauma Surgery, Medical University of Vienna, Vienna, Austria.
3
Department of Anaesthesia, Intensive Care Medicine, and Pain Therapy, Medical University of Vienna, Vienna, Austria.
4
Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
5
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria markus.zeitlinger@meduniwien.ac.at.

Abstract

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.

KEYWORDS:

bacteria; drug tissue concentration; in vivo pharmacokinetics; microdialysis; septic arthritis

PMID:
28784675
PMCID:
PMC5610482
DOI:
10.1128/AAC.00992-17
[Indexed for MEDLINE]
Free PMC Article

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