College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Alaska Native Medical Center, Anchorage, AK, USA.
Int J Antimicrob Agents. 2019 Aug;54(2):197-201. doi: 10.1016/j.ijantimicag.2019.04.010. Epub 2019 Apr 26.
The optimal therapy for serious enterococcal infections, especially vancomycin-resistant enterococci (VRE), remains unclear, although combination therapy is often recommended. Oritavancin has demonstrated in-vitro activity against VRE, but data evaluating oritavancin in combination with other agents and in in-vivo systems are lacking. The objective of this study was to evaluate the efficacy of oritavancin alone and in combination with ceftriaxone, daptomycin, gentamicin, linezolid and rifampin against vancomycin-susceptible enterococci and VRE in an in-vivo Galleria mellonella survival model.
Five enterococcal strains were used: three clinical isolates (VRE S38141, VRE H19570, VRE W21579), Enterococcus faecium ATCC 700221 and Enterococcus faecalis ATCC 29212. G. mellonella larvae were inoculated with the test strain followed by the test drug at humanized weight-based dose alone or in combination within 1 h of inoculation. After injection, larvae were incubated at 37°C and survival was measured daily for 7 days. Survival was plotted using the Kaplan-Meier method, and differences between groups were determined via the log-rank test. Mean survival times were also determined.
Each single agent improved survival significantly compared with the untreated control strain. Oritavancin was the most efficacious single agent, and led to a significant increase in survival compared with ceftriaxone, gentamicin and daptomycin. Compared with oritavancin alone, none of the oritavancin combinations tested were significantly better, and mean survival times were comparable.
Oritavancin monotherapy had the highest survival rate at 7 days, and none of the combinations tested showed improved survival over oritavancin alone. These data add to the body of literature rebutting the routine use of combination therapy with oritavancin for the treatment of infections due to VRE.
严重肠球菌感染（尤其是耐万古霉素肠球菌[VRE]）的最佳治疗方法仍不明确，尽管常推荐联合治疗。奥他万古霉素对 VRE 具有体外活性，但缺乏评估奥他万古霉素联合其他药物及体内系统的疗效的数据。本研究旨在评估奥他万古霉素单药治疗及与头孢曲松、达托霉素、庆大霉素、利奈唑胺和利福平联合治疗对耐万古霉素肠球菌和 VRE 的疗效，采用体内大蜡螟存活模型进行研究。
使用 5 株肠球菌菌株：3 株临床分离株（VRE S38141、VRE H19570、VRE W21579）、粪肠球菌 ATCC 700221 和屎肠球菌 ATCC 29212。在接种测试菌株后 1 h 内，按人体化体重剂量单独或联合使用测试药物对大蜡螟幼虫进行接种。注射后，将幼虫在 37°C 下孵育，每天测量存活情况，共 7 天。采用 Kaplan-Meier 法绘制存活曲线，采用对数秩检验比较组间差异。还确定了平均存活时间。
与未治疗的对照株相比，每种单一药物均显著提高了存活率。奥他万古霉素是最有效的单一药物，与头孢曲松、庆大霉素和达托霉素相比，显著提高了存活率。与奥他万古霉素单药治疗相比，测试的奥他万古霉素联合用药方案均未显著提高存活率，且平均存活时间相当。
奥他万古霉素单药治疗 7 天的存活率最高，测试的联合用药方案均未提高奥他万古霉素单药治疗的存活率。这些数据增加了文献证据，反驳了常规使用奥他万古霉素联合治疗治疗 VRE 感染的做法。
