Zhang Xin, Chen Peng, Wan Hao-Yang, Zhu Run-Jiu, Zhou Yue, Song Ming-Rui, Jiang Nan, Yu Bin
Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Orthopaedics and Traumatology, Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, China.
Front Microbiol. 2022 Nov 3;13:1029261. doi: 10.3389/fmicb.2022.1029261. eCollection 2022.
Growing evidence has shown that the efficacy of systemic administration of daptomycin for the treatment of methicillin-resistant (MRSA)-related infections is satisfactory. However, the clinical efficacy of the local administration of daptomycin for the management of osteoarticular infections remains unclear. This study compared the efficacy of daptomycin and vancomycin against MRSA biofilms. The elution kinetics of daptomycin and vancomycin, combined with gentamicin and loaded with either β-tricalcium phosphate/calcium sulfate or calcium sulfate, in the presence of MRSA infection, was assessed. Their efficacy in preventing biofilm formation and killing pre-formed biofilms was assessed using colony-forming unit count and confocal laser scanning microscopy. In addition, the efficacy of daptomycin, vancomycin, and gentamicin in prophylaxis and eradication of MRSA biofilms was also evaluated. Daptomycin + gentamicin and vancomycin + gentamicin displayed similar antimicrobial potency against MRSA, by either β-tricalcium phosphate/calcium sulfate or calcium sulfate. In the prevention assays, both daptomycin + gentamicin and vancomycin + gentamicin showed similar efficacy in preventing bacterial colony formation, with approximately 6 logs lower colony-forming units than those in the control group at both 1 and 3 days. The killing effect on pre-formed biofilms showed significant decreases of approximately 4 logs at 1 and 3 days following treatment with daptomycin + gentamicin and vancomycin + gentamicin. In addition, the confocal laser scanning microscopy results support the colony-forming unit data. Moreover, single use of vancomycin and gentamicin showed similar efficacies in preventing and killing MRSA biofilms, both of which were better than that of gentamicin. Our study demonstrated that vancomycin + gentamicin and daptomycin + gentamicin loaded with β-tricalcium phosphate/calcium sulfate or calcium sulfate showed similar prophylactic and killing effects on MRSA biofilms, implying a potential indication of local administration daptomycin for the treatment of MRSA-associated osteoarticular infections, especially if vancomycin administration presents limitations.
越来越多的证据表明，全身应用达托霉素治疗耐甲氧西林金黄色葡萄球菌（MRSA）相关感染的疗效令人满意。然而，局部应用达托霉素治疗骨关节炎感染的临床疗效仍不明确。本研究比较了达托霉素和万古霉素对MRSA生物膜的疗效。评估了在存在MRSA感染的情况下，达托霉素和万古霉素与庆大霉素联合使用，并负载于β-磷酸三钙/硫酸钙或硫酸钙中的洗脱动力学。使用菌落形成单位计数和共聚焦激光扫描显微镜评估它们在预防生物膜形成和杀灭预先形成的生物膜方面的疗效。此外，还评估了达托霉素、万古霉素和庆大霉素在预防和根除MRSA生物膜方面的疗效。达托霉素+庆大霉素和万古霉素+庆大霉素对MRSA显示出相似的抗菌效力，无论是负载于β-磷酸三钙/硫酸钙还是硫酸钙中。在预防试验中，达托霉素+庆大霉素和万古霉素+庆大霉素在预防细菌菌落形成方面显示出相似的疗效，在第1天和第3天，菌落形成单位均比对照组低约6个对数。在用达托霉素+庆大霉素和万古霉素+庆大霉素治疗后第1天和第3天，对预先形成的生物膜的杀灭效果显示出显著下降，约4个对数。此外，共聚焦激光扫描显微镜结果支持菌落形成单位数据。此外，单独使用万古霉素和庆大霉素在预防和杀灭MRSA生物膜方面显示出相似的疗效，两者均优于庆大霉素。我们的研究表明，负载于β-磷酸三钙/硫酸钙或硫酸钙中的万古霉素+庆大霉素和达托霉素+庆大霉素对MRSA生物膜显示出相似的预防和杀灭作用，这意味着局部应用达托霉素治疗MRSA相关骨关节炎感染具有潜在的适应证，特别是在万古霉素应用存在局限性的情况下。
