Synergistic Antimicrobial Activity of Colistin in Combination with Rifampin and Azithromycin against Escherichia coli Producing MCR-1.

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 MZ1501^R, isolate HE1704^R that produces MCR-1, and colistin-susceptible isolate MZ1509^S Experiments were conducted with a medium inoculum of ?10⁷ 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.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6256761 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature