In vivo activity of co-trimoxazole combined with colistin against Acinetobacter baumannii producing OXA-23 in a Galleria mellonella model.

Abstract

Acinetobacter baumannii is a critical nosocomial pathogen. A. baumannii infections have become a grave challenge due to their ability to develop resistance to different antimicrobial agents. The current study aimed to evaluate the potential synergism and bactericidal activity of a combination of colistin and cotrimoxazole against carbapenem-resistant A. baumannii (CRAB) in a Galleria mellonella model. Four clinical A. baumannii isolates were biochemically and molecularly identified. Their antimicrobial susceptibility levels were established and the molecular characterization of the carbapenemase-encoding genes was performed. The synergism and bactericidal effect of the colistin/cotrimoxazole combination was assessed using the checkerboard assay and time-kill experiments. An in vivo evaluation of the activity of the combination was performed using the Galleria mellonella model. A fractional inhibitory concentration index (FICI) of ≤0.5 was found for all strains, indicating that the colistin/cotrimoxazole combination exhibited powerful synergistic activity. The combination displayed both synergistic and bactericidal activity at sub-breakpoint concentrations for all strains. Cotrimoxazole monotherapy showed the least protective activity in the G. mellonella model. The survival rate ranged from 66.7-79.2 % at 24 h and was 29.2-60.4 % at 96 h for the tested isolates. Colistin monotherapy performed better than cotrimoxazole monotherapy; the G. mellonella survival rate ranged from 77.1-97.9 %, at 24 h and from 64.5-72. % at 96 h. The colistin/cotrimoxazole combination improved G. mellonella's survival rate at 96 h remarkably in comparison to colistin or cotrimoxazole monotherapy. Finally, the combination of colistin and cotrimoxazole appears to be a promising therapeutic option for the management of CRAB-associated infections. It is essential to assess the clinical application and the dose-response relationships of combinations such as colistin plus cotrimoxazole.