The inoculum effect of Escherichia coli expressing mcr-1 or not on colistin activity in a murine model of peritonitis.

Details

Serval ID
serval:BIB_330C6B5A5105
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The inoculum effect of Escherichia coli expressing mcr-1 or not on colistin activity in a murine model of peritonitis.
Journal
Clinical microbiology and infection
Author(s)
Fantin B., Poujade J., Grégoire N., Chau F., Roujansky A., Kieffer N., Berleur M., Couet W., Nordmann P.
ISSN
1469-0691 (Electronic)
ISSN-L
1198-743X
Publication state
Published
Issued date
12/2019
Peer-reviewed
Oui
Volume
25
Number
12
Pages
1563.e5-1563.e8
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Colistin often remains the last resort antibiotic active against carbapenemase-producing Enterobacteriaceae. However, while in vitro inoculum effect has been reported, therapeutic relevance of this phenomenon remains questioned.
Ten E. coli strains were used that included the wild-type CFT073 and its transconjugant CFT073-MCR-1 and eight susceptible clinical isolates. Mice with peritonitis were treated for 24 h with colistin sulfate. Bacterial loads were determined in peritoneal fluid (PF) and spleen and colistin-resistant mutants were detected.
MICs of colistin against the eight susceptible clinical strains and CFT073 ranged from 0.125 to 0.5 mg/L with an inoculum of 10 <sup>5</sup> CFU/mL and from 2 to 4 mg/L with a 10 <sup>7</sup> CFU/mL inoculum; 5/9 strains with an MIC of 4 mg/L were considered resistant according to EUCAST breakpoint (resistance, > 2 mg/L). When the bacterial load of wild-type CFT073 inoculated in mice increased from 10 <sup>7</sup> to 10 <sup>8</sup> CFU: i) mean log <sub>10</sub> CFU reduction generated by colistin in PF and spleen decreased from 5.8/mL and 3.1/g, respectively, (p < 0.01) to 0.9/mL and 0.8/g, respectively (NS); ii) mice survival rate decreased from 15/15 (100%) to 6/15 (40%) (p = 0.017); and iii) proportion of mice with selection of colistin-resistant mutants increased from 4/15 to 15/15 (p < 0.01). These results were comparable to those obtained when peritonitis was produced with a 10 <sup>7</sup> CFU bacterial load of E. coli CFT073 expressing mcr-1, for which the mean log <sub>10</sub> CFU reductions were 3.5/mL and 0.6/g in PF and spleen, respectively (NS), and survival rate was 8/15 (53%) (p < 0.01 versus survival of mice infected with wild-type CFT073).
Phenotypic colistin resistance in wild-type E. coli due to an increase in inoculum size had a therapeutic impact in mice with peritonitis that was comparable to that observed when the mcr-1 gene was expressed.
Keywords
Animals, Anti-Bacterial Agents/pharmacokinetics, Anti-Bacterial Agents/therapeutic use, Bacterial Load/drug effects, Colistin/pharmacokinetics, Colistin/therapeutic use, Disease Models, Animal, Drug Resistance, Bacterial/genetics, Escherichia coli/drug effects, Escherichia coli/genetics, Escherichia coli/isolation & purification, Escherichia coli Infections/drug therapy, Escherichia coli Infections/microbiology, Escherichia coli Proteins/genetics, Female, Mice, Mice, Inbred ICR, Microbial Sensitivity Tests, Peritonitis/drug therapy, Peritonitis/microbiology, Survival Analysis, Antibiotic resistance, Colistin, Escherichia coli, MCR-1, Peritonitis, Pharmacodynamics
Pubmed
Web of science
Open Access
Yes
Create date
24/09/2019 13:14
Last modification date
20/04/2024 6:56
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