title: In vitro activity of fosfomycin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy.
abstract: Fosfomycin is a molecule that inhibits the early stage of peptidoglycan synthesis and shows a broad-spectrum bactericidal activity against Gram-positive and Gram-negative bacteria. Using the Killing-curve method, we tested the in vitro bactericidal activity of fosfomycin alone or in combination with vancomycin or teicoplanin at a concentration of 8 microg/mL, that is easily achievable in serum at standard dosing regimens, against seven methicillin-resistant Staphylococcus aureus strains, isolated from patients with well documented device-associated infections unresponsive to or relapsing after glycopeptide therapy. MICs of vancomycin ranged from 1 to 4 microg/mL, MICs of teicoplanin from 2 to 8 microg/mL; MICs of fosfomycin were 8 microg/mL for two strains and >128 microg/mL for the remaining strains. The seven strains proved tolerant when tested for vancomycin and teicoplanin used alone at 2x MIC concentration. Fosfomycin was bactericidal (reduction of 2 log of the inoculum) only against the two susceptible strains. In all cases both vancomycin and teicoplanin in combination with fosfomycin developed bactericidal synergism already at a concentration of 1x MIC. If these results are confirmed by in vivo experiments, the combination of fosfomycin with glycopeptides might be useful for treating device-associated infections, and in preventing the phenomenon of increasing MICs for glycopeptides.
authors.affiliation: Servizio di Consulenze Internistico-infettivologiche, III Clinica Medica, Dipartimento di Medicina Clinica-Policlinico Umberto I. Universita di Roma "La Sapienza", Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pistella
authors.forename: Marco
authors.initials: M
authors.lastname: Falcone
authors.forename: Pia
authors.initials: P
authors.lastname: Baiocchi
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Pompeo
authors.forename: Antonio
authors.initials: A
authors.lastname: Pierciaccante
authors.forename: Adrio
authors.initials: A
authors.lastname: Penni
authors.forename: Mario
authors.initials: M
authors.lastname: Venditti
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000209:etiology / Q000382:microbiology*; D001807:Blood Vessel Prosthesis; D002404:Catheterization; D020878:Device Removal; D004322:Drainage; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D016521:Electrophoresis, Gel, Pulsed-Field; D004866:Equipment Contamination; D005578:Fosfomycin / Q000008:administration & dosage / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008480:Mediastinitis / Q000209:etiology / Q000382:microbiology; D016106:Methicillin Resistance; D010138:Pacemaker, Artificial; D011183:Postoperative Complications / Q000382:microbiology; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D017334:Teicoplanin / Q000008:administration & dosage / Q000494:pharmacology*; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D005578:Fosfomycin; D017334:Teicoplanin; D014640:Vancomycin