Mutation prevention parameters of carbapenems against clinical isolates of Pseudomonas and Acinetobacter

Abstract

Treatment failure resulting from bacterial resistance is an issue that has raised significant global concern. The MPC is a pharmacodynamic parameter aimed at limiting the emergence of resistance. Very scarce data regarding this parameter for carbapenems against Pseudomonas spp. and Acinetobacter spp. is available. The aim of this study is to evaluate the MPC of carbapenems against clinical isolates of these bacteria in light of their different mechanisms of resistance. Phenotypic detection of the mechanisms of resistance for 5 clinical isolates of Pseudomonas spp. and Acinetobacter baumannii (each) was performed using: the DDST for the detection of ESBL, the Cefoxitin disk with PBA and the disk antagonism test for the detection of AmpC, the Imipenem disk with PBA/EDTA tests for the detection of MBL and KPC respectively, the effect of added NaCl to the media on the MIC for the detection of OXA, and the CCCP test for the detection of over-production of efflux pumps. The MIC was determined through the broth macrodilution method and the MPC was determined using the plate dilution method. The MPI and MSW were subsequently calculated. Four Acinetobacter baumannii strains and two Pseudomonas spp. strains were resistant to carbapenems. All four Acinetobacter baumannii strains produced MBL, two strains produced OXA, and one produced ESBL. The two carbapenem resistant Pseudomonas spp. isolates produced KPC and MBL. Only one of these strains had plasmidic AmpC. The resistant Acinetobacter spp. strains had higher MPC averages (108.75µg/mL for Meropenem and 318µg/mL for Imipenem) than susceptible ones (70µg/mL for Meropenem and 4µg/mL for Imipenem). The resistant Pseudomonas spp. also had higher MPC values (24µg/mL for Meropenem and 95µg/mL for Imipenem) than susceptible ones (6.5µg/mL for Meropenem and 16.67µg/mL for Imipenem). The MSW was found to be dependant of the degree of resistance of the strain but not on a particular mechanism of resistance. Moreover, the MPI values obtained for Imipenem and Meropenem did not fall within the range reported by other studies. The wider MSW for resistant strains could be reflexive of the fact that already resistant strains are suppressed with increasing difficulty due to the accumulation of mutations. It is proposed that the MPC parameter should be determined for each individual isolate since generalization of the data may not be applicable for carbapenems against these bacteria.