Mutant prevention concentrations of ciprofloxacin against urinary isolates of Escherichia coli and Klebsiella pneumoniae

Ziad Daoud,Elie Salem Sokhn,Khalil Masri,Shira Doron,Eid Azar

doi:10.3855/jidc.3164

Abstract

The aim of this work was to study the ability of ciprofloxacin to restrict the development of resistant mutants of Escherichia coli and Klebsiella pneumoniae through determination of the Mutant Prevention Concentration (MPC). We studied 140 strains of E. coli and 86 strains of K. pneumoniae with different profiles of sensitivity to fluoroquinolones and extended spectrum beta lactamase (ESBL) production. The MPCs were determined using an inoculum of 1010 CFU/ml in Mueller-Hinton agar plates with serial concentrations of ciprofloxacin. Ciprofloxacin-susceptible ESBL-producing strains showed a higher MPC for ciprofloxacin (P <0.001) than ciprofloxacin-susceptible non ESBL-producing strains, while ciprofloxacin-resistant ESBL-producing and non ESBL-producing strains did not significantly differ. The presence of qnr variants was associated with elevated MPCs. This was observed for both tested organisms. Our study helps to explain the frequent finding of resistance to fluoroquinolones in ESBL-producing strains. Consequently, the use of concentrations of ciprofloxacin higher than the MIC in order to prevent the recovery and growth of resistant mutants is recommended.

Highlights

The aim of this work was to study the ability of ciprofloxacin to restrict the development of resistant mutants of Escherichia coli and Klebsiella pneumoniae through determination of the Mutant Prevention Concentration (MPC)
Our study helps to explain the frequent finding of resistance to fluoroquinolones in extended spectrum beta lactamase (ESBL)-producing strains
No significant differences were seen between the Minimum Inhibitory Concentrations (MIC) of this antibiotic in ciprofloxacin-susceptible ESBLproducing and ESBL-non producing strains for both E. coli and K. pneumoniae

Summary

Introduction

The aim of this work was to study the ability of ciprofloxacin to restrict the development of resistant mutants of Escherichia coli and Klebsiella pneumoniae through determination of the Mutant Prevention Concentration (MPC). Quinolones are one of the most widely used antibiotics to treat infections caused by Escherichia coli and Klebsiella pneumoniae in humans and in animals [1]. Resistance to these antibiotics has increased in the recent years and is especially high in extended spectrum beta lactamase (ESBL) producing strains [2,3]. The Mutant Prevention Concentration (MPC) was defined as a useful parameter that prevents/interferes with the emergence and growth of resistant mutants [8]. When used to describe quinolones, the MPC represents the drug concentration that would require an organism to possess two resistance mutations in order to grow in the presence of the drug, and it is equal to the MIC of the most resistant singlemutation organism in a heterogeneous population

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