Meropenem-Vaborbactam Tested against Contemporary Gram-Negative Isolates Collected Worldwide During 2014, Including Carbapenem-Resistant, KPC-Producing, Multidrug-Resistant, and Extensively Drug-Resistant Enterobacteriaceae [PublishAheadOfPrint]

We evaluated the activity of meropenem-vaborbactam against contemporary non-fastidious gram-negative clinical isolates, including resistant phenotypes and carbapenemase genotypes of Enterobacteriaceae. Meropenem-vaborbactam (inhibitor at 8 μg/ml) and comparators were susceptibility tested using reference broth microdilution methods against 14,304 gram-negative clinical isolates collected worldwide during 2014. Carbapenemase encoding genes were screened by PCR/sequencing. Meropenem-vaborbactam (MIC_50/90, ≤0.015/0.06 μg/ml) inhibited 99.1 and 99.3% of the 10,426 Enterobacteriaceae isolates tested at ≤1 and ≤2 μg/ml, respectively. Meropenem inhibited 97.3 and 97.7% of these isolates at the same concentrations. Against Enterobacteriaceae displaying carbapenem resistance (CRE) (n=265), multidrug (MDR) (n=1,210) or extensively drug (XDR) (n=161) resistant phenotypes, meropenem-vaborbactam displayed MIC_50/90 values at 0.5/32, 0.03/1 and 0.5/32 μg/ml, respectively, whereas meropenem activity was 16/>32, 0.06/32 and 0.5/32 μg/ml, respectively. Among all geographic regions, the highest meropenem-vaborbactam activity was observed for CRE and MDR isolates from the U.S. (MIC_50/90, 0.03/1 and 0.03/0.12 μg/ml, respectively). Meropenem-vaborbactam was very active against 135 KPC-producers, and all isolates were inhibited by ≤8 μg/ml (133 isolates at ≤2 μg/ml). This combination had limited activity against isolates producing metallo-β-lactamases (including 25 NDM-1- and 16 VIM-producers) and/or oxacillinases (27 OXA-48/-163) that were detected mainly in Asia-Pacific and some European countries. The activity of meropenem-vaborbactam was similar to that of meropenem alone against Pseudomonas aeruginosa, Acinetobacter spp. and Stenotrophomonas maltophilia. Meropenem-vaborbactam was active against contemporary Enterobacteriaceae collected worldwide, and this combination demonstrated enhanced activity when compared to meropenem and most comparator agents against CRE and KPC-producers that are often MDR.

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