Antibiotic resistance assessment and multi-drug efflux pumps of Enterococcus faecium isolated from clinical specimens

Enterococcus faecium is a major cause of community and hospital-acquired infections. Due to limited options for infection with fluoroquinolones-resistant Enterococci, novel therapeutics are urgently needed. Efflux pumps are contributed to fluoroquinolones resistance phenotype in this bacterium and novel inhibitors that target these efflux pumps could be effective in patients. In this research, the possible synergistic effect of an efflux pump inhibitor (EPI), thioridazine, with ciprofloxacin was investigated against clinical isolates of E. faecium.

A total of 88 isolates of E. faecium from clinical specimens were studied from August 2017 to September 2018. Conventional phenotypic and molecular methods characterized all the isolates. Standard susceptibility tests and molecular assays determined the antibiotic resistance profiles and the frequency of efflux pump genes. Minimum inhibitory concentrations (MICs) to ciprofloxacin (CIP) in the presence and absence of thioridazine were measured by the micro-broth dilution method.

The highest antibiotic resistance rate among E. faecium isolates was related to ciprofloxacin (96.8%), levofloxacin (94.3%), and imipenem (90.9%), respectively. The highest frequency of efflux pump determinants was related to efmA (60, 68%), followed by emeA (48, 54.5%), and efrA and/or efrB genes (45, 51%). The efflux pump inhibitor showed ≥ 2-fold decrease in the MIC value of ciprofloxacin in 48.2% of the isolates.

Efflux pump inhibitor genes efrAB, efmA, and emeA are common among the E. faecium clinical isolates. Our results supported the administration of thioridazine, as an efflux pump inhibitor, in fluoroquinolone-resistant E. faecium infections due to its synergistic effect with CIP.