Effects of KPC variant and porin genotype on the in vitro activity of meropenem-vaborbactam against carbapenem-resistant Enterobacteriaceae.

We described the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory engineered E. coli harboring mutant bla KPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam minimum inhibitory concentrations (MICs) were 1 and 0.03μg/mL, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MIC ≤4μg/mL). Against K. pneumoniae harboring mutant bla KPC, the addition of vaborbactam lowered meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against KPC-producing K. pneumoniae with mutant (n=26) versus wild-type (n=54) ompK36 porin genes (0.25 vs 0.03μg/mL; P<0.0001). Against E. coli TOP10 with plasmid constructs containing wild-type bla KPC or mutant bla KPC, the addition of vaborbactam 8μg/mL lowered meropenem MICs 2 - 512-fold, resulting in meropenem-vaborbactam MICs 0.03 μg/mL. Rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged between 90 and 95%. Essential agreement rates were higher for gradient strips manufactured by bioMérieux (82%) compared to Liofilchem (48%; P<0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research