Journal article 157 views
Novel partners with colistin to increase its in vivo therapeutic effectiveness and prevent the occurrence of colistin resistance in NDM- and MCR-co-producing Escherichia coli in a murine infection model
,
Yang Wang,
Xiao-Ping Liao,
Jian Sun,
Ya-Hong Liu
Journal of Antimicrobial Chemotherapy, Volume: 74, Issue: 1, Pages: 87 - 95
Swansea University Author:
Jon Tyrrell
Full text not available from this repository: check for access using links below.
DOI (Published version): 10.1093/jac/dky413
Abstract
ObjectivesThe emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existin...
| Published in: | Journal of Antimicrobial Chemotherapy |
|---|---|
| ISSN: | 0305-7453 1460-2091 |
| Published: |
Oxford University Press (OUP)
2018
|
| Online Access: |
Check full text
|
| URI: | https://cronfa.swan.ac.uk/Record/cronfa70438 |
| Abstract: |
ObjectivesThe emergence of NDM- and MCR-1-co-producing Escherichia coli has compromised the use of carbapenems and colistin, which are critically important in clinical therapy, and represents a severe threat to public health worldwide. Here, we demonstrate synergism of colistin combined with existing antibiotics as a potential strategy to overcome XDR E. coli co-harbouring NDM and MCR-1 genes.MethodsTo comprehensively evaluate their combined activity, antibiotic combinations were tested against 34 different E. coli strains carrying both NDM and MCR-1 genes. Antibiotic resistance profiles and molecular characteristics were investigated by susceptibility testing, PCR, MLST, S1-PFGE and WGS. Antibiotic synergistic efficacy was evaluated through in vitro chequerboard experiments and dose–response assays. A mouse model was used to confirm active combination therapies. Additionally, combinations were tested for their ability to prevent high-level colistin-resistant mutants (HLCRMs).ResultsCombinations of colistin with rifampicin, rifabutin and minocycline showed synergistic activity against 34 XDR NDM- and MCR-1-co-producing E. coli strains, restoring, in part, susceptibility to both colistin and the partnering antibiotics. The therapeutic effectiveness of colistin combined with rifampicin or minocycline was demonstrated in a mouse model. Furthermore, colistin plus rifampicin showed significant activity in preventing the occurrence of HLCRMs.ConclusionsThe synergism of colistin in combinations with rifampicin, rifabutin or minocycline offers viable therapeutic alternatives against XDR NDM- and MCR-positive E. coli. |
|---|---|
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
This work was supported by the General Program of National Natural Science Foundation of China (Grant No. 31772793), and the Key Program of the National Natural Science Foundation of China (Grant No. 31730097). Y. Y. was funded by the Graduate Student Overseas Study Program of South China Agricultural University (Grant No. 2017LHPY026). |
| Issue: |
1 |
| Start Page: |
87 |
| End Page: |
95 |