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

Abstract

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). Methodology: 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 10 10 CFU/ml in Mueller-Hinton agar plates with serial concentrations of ciprofloxacin. Results: 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.

Mutant Prevention Concentration of Ciprofloxacin against Klebsiella pneumoniae Clinical Isolates: An Ideal Prognosticator in Treating Multidrug-Resistant Strains

“…As these strains frequently cause urinary tract infections, cross resistance with fluoroquinolones is a very challenging issue since intravenous therapy is not recommended in these infections except for the most serious one (pyelonephritis). Fluoroquinolone resistance among the ESBL strains is an added burden in treating patients with complicated UTI [29]. In our study, 11 out of 20 ciprofloxacin-resistant isolates were also ESBL producers.…”

“…Such resistant mutants may be associated with treatment failures and surfacing of resistance [28]. MPC represents a concentration threshhold above which increase of resistant mutants occurs rarely [29]. It appeared that the MPC might serve as a simple measure of antibiotic potency that incorporates the ability of a compound to restrict a selection of resistant mutants [30].…”

“…The mutant selection window (MSW) defines the range of drug concentration in which resistant mutants develop easily. The upper limit of the MSW is the MPC value and the lower limit is the MIC value [29].…”

Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae

“…With respect to the impact of PMQR mechanisms, data from an animal model suggest a reduced efficacy of ciprofloxacin or levofloxacin. The presence of qnr genes also increased the mutant prevention concentration (MPC) (136)(137)(138)(139)(140)(141). The clinical impact of PMQR mechanisms has been studied in only a few observational studies, with discrepant results.…”

Pharmacokinetic/pharmacodynamic based dosing of ciprofloxacin in complicated urinary tract infections

“…Ciprofloxacin and other fluoroquinolones have become a popular treatment option for patients with complicated urinary tract infections in areas with higher rates of resistance to traditionally used antibacterial agents such as trimethoprimsulfamethoxazole and aminopenicillins (Van Bambeke et al, 2005;Finch, 2000). However, excessive use of ciprofloxacin that has led to a considerable and worrying increase in the rate of resistant isolates (Daoud et al, 2014) which raises a question of adequacy of current dosing strategies. The outcome of antibiotic treatment depends on several complex interactions between the infectious agent, antimicrobial drug and host defense mechanisms, and treatment outcome shows high variability of the dose-response relationship (Jacobs, 2001;Wilspelwey, 2005).…”