Collateral sensitivity in clinical Escherichia coli isolates resistant to ciprofloxacin

Abstract

The increase in antimicrobial resistance in bacteria is a serious problem in public heath limiting the efficacy of available antimicrobials for treatment of infections. E. coli is the most frequent cause of uncomplicated urinary tract infections. Ciprofloxacin is an important antimicrobial for treatment of uncomplicated urinary tract infections. Unfortunately, resistance to ciprofloxacin is commonly found in the clinics and confers cross-resistance to other antimicrobials. Recent studies on a previously discovered phenomenon known as collateral sensitivity, the opposite of cross-resistance, where resistance to one antimicrobial confers increased sensitivity to others. Recently, some have suggested that using collateral sensitivity to choose the order of antimicrobial used can beneficially slow the progress of antimicrobial resistance during drug cycling. Therefore, we aim to study the collateral sensitivity and cross-resistance profiles across different clinical isolates of E. coli from urinary tract infections. In this study we generated 10 ciprofloxacin resistant mutants and tested their susceptibility to 8 different antimicrobials. Our results show that E. coli resistant to ciprofloxacin above clinical breakpoints are cross-resistant to many other clinically-relevant antimicrobials, such as mecillinam, trimethoprim, nitrofurantoin, chloramphenicol, and ceftazidime. Our results also showed that ciprofloxacin resistant mutants are collaterally sensitive to gentamicin. This study provides important data on cross-resistance and collateral sensitivity in a collection of clinical E. coli isolates resistant to ciprofloxacin. Since it is important to confirm previous findings on laboratory strains with clinical isolates, hopefully these findings will add to growing data on collateral sensitivity and inform future drug cycling treatment strategies to combat antimicrobial resistance.