JAC Advance Access published online on March 28, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg187
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original Article
1 Department of Clinical
Pharmacology, Division of Clinical Pharmacokinetics, University
of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel
18-20, A-1090 Vienna; Department
of Cardiology,
Division of Intensive Care Medicine, University of Vienna Medical
School, Vienna
* Corresponding author. E-mail: christian.joukhadar{at}univie.ac.at.
Received 14 September 2002
; revised 13 December 2002
; 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
Target site penetration of fosfomycin in critically
ill patients
2 Department of Clinical
Pharmacology, Division of Clinical Pharmacokinetics, University
of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel
18-20, A-1090 Vienna
3 Department
of Pharmacology, Karl-Franzens University, Graz
4 Department
of Cardiology,
Division of Intensive Care Medicine, University of Vienna Medical
School, Vienna
5 Department of Emergency Medicine,
University of Vienna Medical School, Vienna, Austria
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