Gatin Laure, Saleh-Mghir Azzam, Tasse Jason, Ghout Idir, Laurent Frédéric, Crémieux Anne-Claude
EA 3647, Faculté de Médecine Paris-Île-de-France Ouest, Université Versailles Saint-Quentin en Yvelines, Hôpital Raymond Poincaré, Garches, France.
Laboratoire de Bactériologie, Hôpital de la Croix Rousse, Centre National de Référence des Staphylocoques, INSERM Unité 851, Faculté de Médecine Lyon-Est, Lyon, France.
Antimicrob Agents Chemother. 2014 Nov;58(11):6496-500. doi: 10.1128/AAC.03600-14. Epub 2014 Aug 18.
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.
头孢洛林（CPT）是前药头孢洛林磷酰胺（CPT-F）的活性代谢产物，在体外对耐甲氧西林金黄色葡萄球菌（MRSA）具有杀菌活性，并且在难治性MRSA心内膜炎和急性骨髓炎的兔模型中有效。然而，其在人工关节感染（PJI）模型中的体内疗效尚不清楚。使用兔MRSA感染的膝关节PJI模型，比较了CPT-F或万古霉素（VAN）单独使用以及与利福平（RIF）联合使用的疗效。在用适合胫骨骨髓腔的硅胶植入物进行每次部分膝关节置换后，将5×10⁷MRSA菌落形成单位（CPT、RIF和VAN的最低抑菌浓度分别为0.38、0.006和1mg/升）注入膝关节。感染动物在接种后7天随机分组接受不治疗（对照组）或CPT-F（60mg/kg体重肌内注射[i.m.]）、VAN（60mg/kg i.m.）、CPT-F加RIF（10mg/kg i.m.）或VAN加RIF治疗，持续7天。治疗结束后3天对粉碎的胫骨中的存活细菌进行计数。尽管CPT治疗组（3.0±0.9，n = 12）和VAN治疗组（3.5±1.1，n = 12）粉碎骨的体内平均log₁₀CFU/g显著低于对照组（5.6±1.1，n = 14）（P < 0.001），但两种治疗均未完全清除骨内细菌（每种治疗均有3/12无菌）。抗生素与RIF联合使用时，CPT-F的平均log₁₀CFU/g值为1.9±0.5（12/14无菌），VAN为1.9±0.5（12/14无菌）。在该MRSA PJI模型中，CPT-F和VAN的疗效无差异；因此，CPT似乎是治疗MRSA PJI的一种有前景的抗菌药物。
