College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Loyola University Medical Center, Maywood, IL, USA.
J Antimicrob Chemother. 2019 May 1;74(5):1300-1305. doi: 10.1093/jac/dkz010.
The optimal treatment for serious infections due to Enterococcus spp. is unknown although combination antimicrobial therapy is often recommended for invasive infections to achieve bactericidal activity and improve clinical outcomes. Oritavancin is a novel lipoglycopeptide agent with in vitro activity against enterococci, including vancomycin-resistant VanA-type Enterococcus faecium. Data on its activity in combination with other antibacterials are limited. The objective of this study was to evaluate the activity of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampicin against vancomycin-susceptible and -resistant enterococci in in vitro time-kill analyses.
Five enterococcal strains were used for all experiments: three vancomycin-resistant VanA-type E. faecium clinical bloodstream isolates, vancomycin-resistant VanA-type E. faecium ATCC 700221 and vancomycin-susceptible Enterococcus faecalis ATCC 29212. Individual drugs were tested at ¼, ½, 1, 2 and 4× MIC. Oritavancin combination experiments were performed with each agent at ¼× MIC.
Daptomycin was the most active single agent and was bactericidal against all strains at 4× MIC, followed by oritavancin, which was bactericidal against all three clinical VRE strains at ≥2× MIC. In combination experiments at ¼× MIC, oritavancin was synergistic with gentamicin against strains not displaying high-level aminoglycoside resistance. No other synergy against VRE strains was observed in any experiment. Strain- and drug-dependent antagonism was observed for many combinations.
These in vitro data do not support the routine use of combination therapy with oritavancin in the treatment of infections due to VRE.
肠球菌属引起的严重感染的最佳治疗方法尚不清楚，尽管侵袭性感染常推荐联合抗菌治疗以实现杀菌活性并改善临床结局。奥利万星是一种新型糖肽类药物，对肠球菌具有体外活性，包括耐万古霉素的 VanA 型屎肠球菌。关于其与其他抗菌药物联合应用的活性数据有限。本研究的目的是评估奥利万星单独及与头孢曲松、达托霉素、庆大霉素、利奈唑胺和利福平联合应用对耐万古霉素和敏感肠球菌的体外时间杀伤分析活性。
所有实验均使用 5 株肠球菌菌株：3 株耐万古霉素的 VanA 型屎肠球菌临床血流分离株、耐万古霉素的 VanA 型屎肠球菌 ATCC 700221 和万古霉素敏感的粪肠球菌 ATCC 29212。单独药物在 1/4、1/2、1、2 和 4×MIC 下进行测试。奥利万星联合实验中，各药物在 1/4×MIC 下进行。
达托霉素是最有效的单一药物，在 4×MIC 下对所有菌株均具有杀菌活性，其次是奥利万星，在≥2×MIC 下对所有 3 株临床 VRE 菌株均具有杀菌活性。在 1/4×MIC 的联合实验中，奥利万星与庆大霉素联合对未显示高水平氨基糖苷类耐药的菌株具有协同作用。在任何实验中均未观察到对 VRE 菌株的其他协同作用。观察到许多组合存在菌株和药物依赖性拮抗作用。
这些体外数据不支持常规使用奥利万星联合治疗耐万古霉素肠球菌感染。
