Dataset Information

Activity of Tigecycline or Colistin in Combination with Zidovudine against Escherichia coli Harboring tet(X) and mcr-1.

ABSTRACT: Alternative therapeutic options are urgently needed against multidrug-resistant Escherichia coli infections, especially in situations of preexisting tigecycline and colistin resistance. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tigecycline/colistin combinations achieved synergistic killing and significantly decreased bacterial burdens by >2.5-log10 CFU/g in thigh tissues compared to each monotherapy.

SUBMITTER: Zhou YF

PROVIDER: S-EPMC7927862 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Activity of Tigecycline or Colistin in Combination with Zidovudine against Escherichia coli Harboring tet(X) and mcr-1.

Zhou Yu-Feng YF Liu Ping P Dai Shu-He SH Sun Jian J Liu Ya-Hong YH Liao Xiao-Ping XP

Antimicrobial agents and chemotherapy 20201216 1

Alternative therapeutic options are urgently needed against multidrug-resistant Escherichia coli infections, especially in situations of preexisting tigecycline and colistin resistance. Here, we investigated synergistic activity of the antiretroviral drug zidovudine in combination with tigecycline or colistin against E. coli harboring tet(X) and mcr-1 in vitro and in a murine thigh infection model. Zidovudine and tigecycline/colistin combinations achieved synergistic ...[more]

PMID: 33020156

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Project description:The spread of colistin-resistant bacteria among rural community residents of low- and middle-income countries is a major threat to community health. Although the mechanism of the spread of colistin-resistant bacteria in communities is unknown, geographic and regional characteristics may influence it. To elucidate the spread mechanism of colistin-resistant bacteria, we analyzed the genomes of colistin-resistant Escherichia coli isolated from Vietnam and Ecuador residents, which are geographically and socially different. Stool specimens of 139 and 98 healthy residents from Ecuador and Vietnam rural communities, respectively, were analyzed for colistin-resistant E. coli with mcr. Its prevalence in the residents of all the communities assessed was high and approximately equal in both countries: 71.8% in Ecuador and 69.4% in Vietnam. A phylogenetic tree analysis revealed that the sequence type of colistin-resistant E. coli was diverse and the major sequence types were different between the two countries. The location of mcr in the isolates showed that the proportion of chromosomal mcr was 35.1% and 8.5% in the Vietnam and Ecuador isolates, respectively. Most of these chromosomal mcr genes (75%-76%) had an intact mcr-transposon Tn6330. Contrastingly, the replicon types of the mcr-carrying-plasmids were diverse in both countries, but almost all belonged to IncI2 in Ecuador and IncX1/X4 in Vietnam. Approximately 26%-45% of these mcr-plasmids had other resistance genes, which also varied between countries. These results suggest that although the overall profile of the colistin-resistant E. coli isolates is diverse in these countries, the phylogenesis of the isolates and mcr-carrying plasmids has regional characteristics. Although the contributing factors are not clear, it is obvious that the overall profile of colistin-resistant bacteria dissemination varies between countries. Such different epidemic patterns are important for establishing country-specific countermeasures against colistin-resistant bacteria.

Dataset Information

Activity of Tigecycline or Colistin in Combination with Zidovudine against Escherichia coli Harboring tet(X) and mcr-1.

Publications

Activity of Tigecycline or Colistin in Combination with Zidovudine against Escherichia coli Harboring <i>tet</i>(X) and <i>mcr-1</i>.

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