Microbiological efficiency of the combinations of two carbapenems against antibiotic resistant Klebsiella pneumoniae strains

Abstract

Combined antibiotic therapy is widely used for infections caused by carbapenem-resistant K. pneumoniae. The objective of this work was to identify the synergistic activity of combinations of two carbapenems against multidrug- and extensively drug-resistant K. pneumoniae strains producing various types of carbapenemases. For 60 antibiotic-resistant K. pneumoniae strains isolated in 8 cities of Belarus, the minimum inhibitory concentrations (MIC) of colistin and carbapenems were determined by subsequent broth microdilution method, and the genes of carbapenemases and phosphoethanolamine transferases were detected. The checkerboard method was used to determine the sensitivity to the combination of ertapenem and doripenem. High MIC values of carbapenems were revealed for NDM carbapenemase-producing strains (MIC50 of meropenem 64 mg/L, MIC50 of doripenem 64 mg/L). Doripenem was more active; MIC of doripenem ≤ 16 mg/L (low level of resistance) was determined in 28 (46.7%) strains, MIC of meropenem ≤ 16 mg/L - in 8 (13.3% of strains). The effect of potentiating the activity of doripenem with ertapenem at a fixed pharmacokinetic / pharmacodynamic concentration was observed for 20.0% of the strains producing KPC carbapenemase and 29.0% of the strains producing OXA-48 carbapenemase. The potentiating effect was independent of the presence of colistin resistance. Thus, the ability of ertapenem to potentiate the antimicrobial activity of doripenem and meropenem against some of the strains producing serine carbapenemases (KPC and OXA-48) was confirmed. The necessity of routine determination of the true MIC values of carbapenems was shown to optimize their dosage regimens and select the combination antibiotic therapy regimens.