title: Target site bacterial killing of cefpirome and fosfomycin in critically ill patients.
abstract: We employed an in-vivo pharmacokinetic/in-vitro pharmacodynamic method to simulate bacterial killing in plasma and the interstitium of skeletal muscle tissue after intravenous administration of 2 g of cefpirome and 8 g of fosfomycin alone and in combination to patients with sepsis. Interstitial antimicrobial concentrations were determined by use of in-vivo microdialysis. CFU/ml of Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (clinical isolate) decreased by approximately 2log(10) for plasma and muscle tissue 6 h after cefpirome and fosfomycin administration compared with the baseline, respectively. The simulation of plasma and tissue pharmacokinetics for the combined administration of these antibiotics resulted in complete eradication of S. aureus within 5 h after drug exposure. No bacterial re-growth occurred in any of the simulations within 6 h. The in-vitro simulation of in-vivo plasma and tissue pharmacokinetics of cefpirome and fosfomycin has shown that both antimicrobial agents kill S. aureus and P. aeruginosa strains effectively after single dose administration. This effect was most pronounced by the combined use of these antimicrobial agents. Therefore, this data corroborates antimicrobial strategies of simultaneous administration of cefpirome and fosfomycin in patients with severe soft tissue infection.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Vienna University School of Medicine, Allgemeines Krankenhaus, Währinger Gürtel 18-20, A-1090, Vienna, Austria.
authors.forename: M A
authors.initials: MA
authors.lastname: Zeitlinger
authors.forename: C
authors.initials: C
authors.lastname: Marsik
authors.forename: A
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Heinz
authors.forename: C
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D015169:Colony Count, Microbial; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D005578:Fosfomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D000097572:Cefpirome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005578:Fosfomycin; D000097572:Cefpirome