Evaluation of the In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae [PublishAheadOfPrint]

Vaborbactam (formerly RPX7009) is a novel inhibitor of serine β-lactamases, including Ambler class A carbapenemases such as KPCs. The current study evaluated the in vitro activity of the combination agent meropenem-vaborbactam against a 2014-2015 global collection of 991 isolates of KPC-positive Enterobacteriaceae using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. The concentration of meropenem (when tested with a fixed concentration of 8 μg/ml of vaborbactam) that inhibited 90% of isolates of KPC-positive Enterobacteriaceae (MIC₉₀) was 1 μg/ml, and MIC values ranged from ≤0.03->32 μg/ml; 99.0% (981/991) of isolates had meropenem-vaborbactam MICs ≤4 μg/ml, the FDA-approved susceptible MIC breakpoint for meropenem-vaborbactam (Vabomere^™). Vaborbactam lowered the meropenem MIC₅₀ from 32 to 0.06 μg/ml and the MIC₉₀ from >32 to 1 μg/ml, respectively. There were no differences in the activity of meropenem-vaborbactam stratifying isolates by KPC variant type. We conclude that meropenem-vaborbactam demonstrated potent in vitro activity against a 2014-2015, worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae.

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