Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, UK.
Department of Microbiology, The General Infirmary at Leeds, Leeds LS1 3EX, UK.
Int J Antimicrob Agents. 2017 Apr;49(4):507-511. doi: 10.1016/j.ijantimicag.2016.12.006. Epub 2017 Feb 21.
Enterococci are a leading cause of healthcare-associated infection worldwide and display increasing levels of resistance to many of the commonly used antimicrobials, making treatment of their infections challenging. Combinations of antibiotics are occasionally employed to treat serious infections, allowing for the possibility of synergistic killing. The aim of this study was to evaluate the effects of different antibacterial combinations against enterococcal isolates using an in vitro approach and an in vivo Galleria mellonella infection model. Five Enterococcus faecalis and three Enterococcus faecium strains were screened by paired combinations of rifampicin, tigecycline, linezolid or vancomycin using the chequerboard dilution method. Antibacterial combinations that displayed synergy were selected for in vivo testing using a G. mellonella larvae infection model. Rifampicin was an effective antibacterial enhancer when used in combination with tigecycline or vancomycin, with minimum inhibitory concentrations (MICs) of each individual antibiotic being reduced by between two and four doubling dilutions, generating fractional inhibitory concentration index (FICI) values between 0.31 and 0.5. Synergy observed with the chequerboard screening assays was subsequently observed in vivo using the G. mellonella model, with combination treatment demonstrating superior protection of larvae post-infection in comparison with antibiotic monotherapy. In particular, rifampicin in combination with tigecycline or vancomycin significantly enhanced larvae survival. Addition of rifampicin to anti-enterococcal treatment regimens warrants further investigation and may prove useful in the treatment of enterococcal infections whilst prolonging the clinically useful life of currently active antibiotics.
肠球菌是全球医疗保健相关感染的主要原因，并且对许多常用的抗菌药物的耐药性不断增加，这使得治疗其感染具有挑战性。抗生素联合使用偶尔用于治疗严重感染，从而有可能产生协同作用。本研究旨在通过体外方法和体内家蚕感染模型评估不同抗菌组合对肠球菌分离株的影响。使用棋盘稀释法对 5 株粪肠球菌和 3 株屎肠球菌进行利福平、替加环素、利奈唑胺或万古霉素的配对组合筛选。对显示协同作用的抗菌组合进行体内测试，使用家蚕幼虫感染模型。利福平与替加环素或万古霉素联合使用时是一种有效的抗菌增强剂，每种单独抗生素的最低抑菌浓度 (MIC) 降低了两个至四个二倍稀释度，生成的部分抑菌浓度指数 (FICI) 值在 0.31 至 0.5 之间。在体内使用家蚕模型观察到棋盘筛选试验中的协同作用，与抗生素单药治疗相比，联合治疗在感染后对幼虫的保护作用更好。特别是利福平与替加环素或万古霉素联合使用可显著提高幼虫的存活率。在抗肠球菌治疗方案中加入利福平值得进一步研究，可能有助于治疗肠球菌感染，同时延长目前有效抗生素的临床使用期限。
