Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Molecular Biology, Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.
J Microbiol Immunol Infect. 2018 Feb;51(1):70-75. doi: 10.1016/j.jmii.2016.01.003. Epub 2016 Jan 29.
BACKGROUND/PURPOSE: To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further.
The antimicrobial activity of colistin alone and in combination with imipenem was assessed versus an imipenem-susceptible isolate, E. cloacae GN1059, or an imipenem-resistant strain, E. cloacae GN0791, isolated in Anhui, China. The potential synergy of imipenem-colistin was evaluated using a checkerboard assay, as well as static time-kill experiments at 1× and 2× minimum inhibitory concentration (MIC). A simple invertebrate model (Galleria mellonella) was developed to assess the in vivo efficacy of imipenem-colistin in treating E. cloacae infection.
In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of ≤ 0.5) was observed between imipenem and colistin for both isolates tested. In time-kill assays, the combination of imipenem-colistin at 1× or 2× MIC resulted in complete killing of both strains. In the G. mellonella larvae model infected with lethal doses of E. cloacae, the combination therapy led to significantly increased survival of the larvae as compared with imipenem or colistin monotherapy alone (p < 0.05).
This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.
背景/目的：研究亚胺培南-黏菌素联合用药对多药耐药阴沟肠杆菌感染的体外和体内活性，以确定是否值得进一步探索。
评估黏菌素单独使用和与亚胺培南联合使用对来自中国安徽的亚胺培南敏感分离株阴沟肠杆菌 GN1059 或亚胺培南耐药株阴沟肠杆菌 GN0791 的抗菌活性。采用棋盘微量稀释法和 1×和 2×最低抑菌浓度（MIC）的静态时间杀伤实验评估亚胺培南-黏菌素的潜在协同作用。建立简单的无脊椎动物模型（家蚕）来评估亚胺培南-黏菌素治疗阴沟肠杆菌感染的体内疗效。
在棋盘微量稀释法中，两种分离株均观察到亚胺培南和黏菌素之间存在协同作用（定义为抑制浓度指数分数≤0.5）。在时间杀伤实验中，1×或 2×MIC 的亚胺培南-黏菌素联合用药可完全杀灭两种菌株。在家蚕幼虫感染阴沟肠杆菌致死剂量的模型中，与亚胺培南或黏菌素单独用药相比，联合治疗可显著提高幼虫的存活率（p<0.05）。
这是首例报道亚胺培南-黏菌素联合用药在阴沟肠杆菌感染家蚕幼虫模型中的疗效。本研究表明，亚胺培南-黏菌素联合用药对阴沟肠杆菌具有高度的体外和简单无脊椎动物模型活性，并提供了初步的体内证据，表明这种联合用药可能具有治疗价值。
