Synergistic Antimicrobial Activity of Colistin in Combination with Rifampin and Azithromycin against Escherichia coli Producing MCR-1.
Antimicrob Agents Chemother
; 62(12)2018 12.
Article
em En
| MEDLINE
| ID: mdl-30224527
ABSTRACT
The lack of available antibiotics is a global public health problem due to the emergence of antimicrobial resistance. Effective therapeutic regimens are urgently needed against Escherichia coli strains that produce the colistin resistance gene mcr-1 and to inhibit the emergence of resistance. In this study, we assessed the antimicrobial activity of a series of concentrations of colistin-based combinations with rifampin and/or azithromycin against three strains of Escherichia coli, including colistin-resistant isolate MZ1501R, isolate HE1704R that produces MCR-1, and colistin-susceptible isolate MZ1509S Experiments were conducted with a medium inoculum of â¼107 CFU/ml over 48 h. Subsequently, the in vivo therapeutic effect was investigated using a neutropenic mouse thigh infection model. Almost all monotherapies showed unsatisfactory antibacterial activity against E. coli isolates producing MCR-1. In contrast, colistin in combination with rifampin or azithromycin resulted in an obvious decrease in the bacterial burden albeit with regrowth. More obviously, synergistic antimicrobial activity of colistin-based triple-combination therapy with rifampin and azithromycin was observed, resulting in a rapid and exhaustive antibacterial effect. In vivo treatments confirmed these findings, where mean decreases of 0.38 to 0.90 log10 CFU and 1.27 to 1.78 log10 CFU were noted after 24 h and 48 h of treatment, respectively, against colistin-resistant E. coli strains when 5 mg/kg of body weight of colistin was combined with rifampin and azithromycin. Colistin-based combinations with rifampin and azithromycin provide a more active therapeutic regimen than monotherapy or colistin-based double combinations against E. coli producing MCR-1.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rifampina
/
Colistina
/
Azitromicina
/
Proteínas de Escherichia coli
/
Escherichia coli
/
Infecções por Escherichia coli
/
Antibacterianos
/
Neutropenia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China