JAC Advance Access originally published online on March 28, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 1247-1252
© 2003 The British Society for Antimicrobial Chemotherapy
Target site penetration of fosfomycin in critically ill patients
1 Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel 18–20, A-1090 Vienna; 2 Department of Cardiology, Division of Intensive Care Medicine, University of Vienna Medical School, Vienna; 3 Department of Pharmacology, Karl-Franzens University, Graz; 4 Department of Emergency Medicine, University of Vienna Medical School, Vienna, Austria
Received 14 September 2002; returned 13 December 2002; revised 2 January 2003; accepted 3 February 2003
Objective: The 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 results: The 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·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.
Conclusion: Fosfomycin 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.
Keywords: sepsis, target site, human, microdialysis
* Corresponding author. Tel: +43-1-40400-2981; Fax: +43-1-40400-2998; E-mail: christian.joukhadar{at}univie.ac.at
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