title: Target site penetration of fosfomycin in critically ill patients.
abstract: 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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, University of Vienna Medical School, Allgemeines Krankenhaus, Waehringer Guertel 18-20, A-1090 Vienna.
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
authors.forename: Nikolas
authors.initials: N
authors.lastname: Klein
authors.forename: Peter
authors.initials: P
authors.lastname: Dittrich
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Alexander
authors.initials: A
authors.lastname: Geppert
authors.forename: Keso
authors.initials: K
authors.lastname: Skhirtladze
authors.forename: Martin
authors.initials: M
authors.lastname: Frossard
authors.forename: Gottfried
authors.initials: G
authors.lastname: Heinz
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D003198:Computer Simulation; D016638:Critical Illness; D005260:Female; D005578:Fosfomycin / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin