Determination of Mutant Prevention Concentration in Extended Spectrum Beta Lactamases Producing Enterobacteriaceae

DOI: 10.26650/experimed.2018.377256 Objectives: The use of carbapenems for treating infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae has increased. Consequently, this practice has resulted in the emergence of carbapenem resistance. In this study, we aimed to determine mutant prevention concentrations (MPCs) of carbapenems and the development of carbapenem resistance in infections caused by ESBL-producing bacteria. Material and Method: The test group included isolates of Escherichia coli and Klebsiella pneumonia that produced imipenem and meropenem minimum inhibitor concentration (MIC)=<1mg/L and at least one of the ESBL (n=56). Negatives isolates (n=19) for all tested enzymes comprised the control group. Carbapenems included in the study were imipenem, meropenem, doripenem, and ertapenem. The MIC and MPC values of these drugs were determined using the agar dilution method for all tested organisms. Results: In ESBL-negative isolates, the MPC90 values were in the susceptible range. In contrast, in the ESBL positive isolates, MPC90 value increased to 2–8 mg/L. The MPC values were 2- to 9-fold higher in the ESBL-producing strains compared with the non-ESBL strains. However, the mutant selection rate was not affected by the ESBL enzymes types (TEM, SHV, and CTX-M). In ESBL-positive strains, imipenem and meropenem, even at very low MICs (0.015–0.06 μg/mL), showed selective carbapenem-resistant mutants at a rate of 50%. Conclusion: Our results suggest the following conclusions. i) ESBL production seems to increase carbapenem resistance in mutant strains, even though these are carbapenem susceptible in routine tests. ii) Among carbapenems, doripenem and ertapenem have the least potential for mutant selection whereas imipenem and meropenem have the most potential