CiproFloxacin hydrochloride monohydrate

Escherichia coli isolates carrying chromosomally-encoded low-level quinolone resistant (LLQR) determinants are frequently found in urinary tract infections (UTI). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin in E. coli However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied become resistant to ciprofloxacin (according to CLSI) under physiological conditions whereas the control strain lacking LLQR mutations does not.

We have analyzed the contribution of different efflux components towards glutathione-mediated abrogation of ciprofloxacin's activity in Escherichia coli and underlying potential mechanism(s) behind this phenomenon. The results indicated that glutathione increased the total active efflux thereby partially contributing towards glutathione-mediated neutralization of ciprofloxacin's antibacterial action in E. coli. However, the role of glutathione-mediated increased efflux becomes evident in the absence of functional TolC-AcrAB efflux pump.