Modulation of antibiotic resistance in clinical isolates of Enterobacter aerogenes - a strategy combining antibiotics and chemosensitisers.

PURPOSE: The main focus of this study was to evaluate the antimicrobial susceptibility profiles of a selected number of human clinical isolates of Enterobacter aerogenes and explore the effects of selected chemosensitisers on the reversal of the resistant phenotype of these isolates.

METHODOLOGY: This study design was accomplished by: (i) characterising several multidrug resistant (MDR) E. aerogenes clinical isolates; (ii) evaluating the contribution of target gene mutations to the resistance phenotype focusing on fluoroquinolones and chloramphenicol only; (iii) evaluating the contribution of membrane permeability and efflux to the MDR phenotype; (iv) assessing the combined action of selected antimicrobials and chemosensitisers (to identify combinations with synergistic effects and able to reduce the MIC); (v) understand how these combinations can modulate the permeability or efflux on these isolates.

RESULTS: Resistance to ciprofloxacin couldn't be totally reversed due to pre-existing mutations in target genes. Chloramphenicol susceptibility was efficiently restored by the addition of the selected chemosensitisers. From the modulation kinetics it was clear that phenothiazines were able to increase the accumulation of the Hoescht dye.

CONCLUSIONS: Modulations of permeability and efflux in the presence of chemosensitisers help us to propose more appropriate chemotherapeutic combinations that can set the model to be used in the treatment of these and other MDR-infections.