期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 57, 期 4, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijantimicag.2021.106309
关键词
Enterobacterales; Colistin; Mefloquine; NDM-1; ESBL; mcr-1
资金
- Helperby Therapeutics Group Ltd.
The combination of mefloquine and colistin showed synergistic activity against multidrug-resistant Enterobacterales in vitro and in vivo, suggesting its potential for rejuvenating the activity of colistin.
Infections caused by carbapenem-resistant Enterobacterales are difficult to treat. Colistin is the last-resort drug for the treatment of these infections, however colistin resistance has emerged in animals and humans. This study investigated the in vitro efficacy of mefloquine in combination with colistin against 114 antibiotic-resistant Enterobacterales isolates including NDM-1, extended-spectrum beta-lactamase (ESBL) and mcr-1 containing strains from a broad range of origins. The effect of the mefloquine and colistin combination was examined in vitro by chequerboard method and time-kill analysis and in vivo in a murine peritoneal infection model. The fractional inhibitory concentration index (FICI) of the combination indicated that synergy was detected for all NDM-1 and mcr-1 containing strains, 87.5% of ESBL producing Escherichia coli and 97.9% of ESBL producing Klebsiella pneumoniae strains. Time-kill curves demonstrated significant synergistic activity with low concentrations of colistin that were boosted by mefloquine. The combination showed enhanced activity against infection with NDM-1- or mcr-1 containing Enterobacteriaceae in mice at 4 h and 6 h after treatment. These findings suggest that the combination of mefloquine and colistin has the potential for rejuvenating the activity of colistin against multidrug-resistant Enterobacterales. (C) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据