title: Ceftaroline-Fosamil efficacy against methicillin-resistant Staphylococcus aureus in a rabbit prosthetic joint infection model.
abstract: Ceftaroline (CPT), the active metabolite of the prodrug ceftaroline-fosamil (CPT-F), demonstrates in vitro bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and is effective in rabbit models of difficult-to-treat MRSA endocarditis and acute osteomyelitis. However, its in vivo efficacy in a prosthetic joint infection (PJI) model is unknown. Using a MRSA-infected knee PJI model in rabbits, the efficacies of CPT-F or vancomycin (VAN) alone and combined with rifampin (RIF) were compared. After each partial knee replacement with a silicone implant that fit into the tibial intramedullary canal was performed, 5 × 10(7) MRSA CFU (MICs of 0.38, 0.006, and 1 mg/liter for CPT, RIF, and VAN, respectively) was injected into the knee. Infected animals were randomly assigned to receive no treatment (controls) or CPT-F (60 mg/kg of body weight intramuscularly [i.m.]), VAN (60 mg/kg i.m.), CPT-F plus RIF (10 mg/kg i.m.), or VAN plus RIF starting 7 days postinoculation and lasting for 7 days. Surviving bacteria in crushed tibias were counted 3 days after ending treatment. Although the in vivo mean log10 CFU/g of CPT-treated (3.0 ± 0.9, n = 12) and VAN-treated (3.5 ± 1.1, n = 12) crushed bones was significantly lower than those of controls (5.6 ± 1.1, n = 14) (P < 0.001), neither treatment fully sterilized the bones (3/12 were sterile with each treatment). The mean log10 CFU/g values for the antibiotics in combination with RIF were 1.9 ± 0.5 (12/14 were sterile) for CPT-F and 1.9 ± 0.5 (12/14 were sterile) for VAN. In this MRSA PJI model, the efficacies of CPT-F and VAN did not differ; thus, CPT appears to be a promising antimicrobial agent for the treatment of MRSA PJIs.
authors.affiliation: EA 3647, Faculté de Médecine Paris-Île-de-France Ouest, Université Versailles Saint-Quentin en Yvelines, Hôpital Raymond Poincaré, Garches, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Gatin
authors.affiliation: EA 3647, Faculté de Médecine Paris-Île-de-France Ouest, Université Versailles Saint-Quentin en Yvelines, Hôpital Raymond Poincaré, Garches, France.
authors.forename: Azzam
authors.initials: A
authors.lastname: Saleh-Mghir
authors.affiliation: Laboratoire de Bactériologie, Hôpital de la Croix Rousse, Centre National de Référence des Staphylocoques, INSERM Unité 851, Faculté de Médecine Lyon-Est, Lyon, France.
authors.forename: Jason
authors.initials: J
authors.lastname: Tasse
authors.affiliation: URC Paris-Ouest Laboratoire de Biostatistiques, Hôpital Ambroise Pare, Boulogne-Billancourt, France.
authors.forename: Idir
authors.initials: I
authors.lastname: Ghout
authors.affiliation: Laboratoire de Bactériologie, Hôpital de la Croix Rousse, Centre National de Référence des Staphylocoques, INSERM Unité 851, Faculté de Médecine Lyon-Est, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Laurent
authors.affiliation: EA 3647, Faculté de Médecine Paris-Île-de-France Ouest, Université Versailles Saint-Quentin en Yvelines, Hôpital Raymond Poincaré, Garches, France anne-claude.cremieux@rpc.aphp.fr.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Crémieux
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D016459:Prosthesis-Related Infections / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D014640:Vancomycin / Q000627:therapeutic use; D000097583:Ceftaroline
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D014640:Vancomycin; D000097583:Ceftaroline