• Christian Joukhadar, Nikolas Klein, Peter Dittrich, Markus Zeitlinger, Alexander Geppert, Keso Skhirtladze, Martin Frossard, Gottfried Heinz, and Markus Müller.
• Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna.
• J. Antimicrob. Chemother. 2003 May 1;51(5):1247-52.

ObjectiveThe present study was undertaken to investigate the target site penetration properties of fosfomycin, an antibiotic particularly suitable for treatment of soft tissue infections (STIs) in critically ill patients.Methods And ResultsThe study population included nine patients with sepsis. Penetration of fosfomycin into the interstitial space fluid of skeletal muscle was measured using the microdialysis technique, following a single intravenous administration of 8.0 g of fosfomycin to patients. The median (range) fosfomycin area under the concentration versus time profile for plasma and skeletal muscle were 673 (459-1108) and 477 (226-860) mg x h/L (P < 0.011), respectively. Interstitial maximum concentrations were lower than plasma values (P < 0.029). Median fosfomycin concentrations in the interstitium and plasma exceeded 70 mg/L throughout the observation period of 4 h and covered MICs for Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa. Simulation of bacterial growth inhibition of S. pyogenes, based on tissue concentration data, confirmed the bactericidal properties of fosfomycin described in previous studies.ConclusionFosfomycin concentrations in muscle interstitium and plasma exceeded the MICs for a range of clinically relevant pathogens in critically ill patients. Thus, fosfomycin exhibits a tissue pharmacokinetic profile, which appears to offer an alternative to other broad-spectrum antibiotics in intensive care patients suffering from STI.

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