Effect of the beta-Lactamase Inhibitor Vaborbactam Combined with Meropenem against Serine Carbapenemase-Producing Enterobacteriaceae.

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Castanheira M, Rhomberg PR, Flamm RK, Jones RN

Effect of the beta-Lactamase Inhibitor Vaborbactam Combined with Meropenem against Serine Carbapenemase-Producing Enterobacteriaceae.

Antimicrob Agents Chemother. 2016 Aug 22;60(9):5454-8. doi: 10.1128/AAC.00711-16. Print 2016 Sep.

PubMed ID
27381386 [ View in PubMed
]
Abstract

Klebsiella pneumoniae carbapenemase (KPC)-producing isolates have become increasingly prevalent worldwide, and these organisms are often multidrug resistant, limiting the therapeutic options available for treating infections. We evaluated the activity of meropenem combined with the serine beta-lactamase inhibitor vaborbactam (formerly RPX7009) against 315 serine carbapenemase-producing Enterobacteriaceae (CPE) isolates by use of checkerboard-designed panels to assess the optimal inhibitor concentration (range tested, 0.5 to 32 mug/ml). Overall, meropenem alone (MIC50 and MIC90, 16 and >64 mug/ml, respectively) inhibited only 2.2% of the isolates at /=8 mug/ml of the inhibitor (>/=96.5% of isolates were inhibited at 64 mug/ml) or displaying decreased expression of OmpK37 and/or elevated expression of the AcrAB-TolC efflux system (MIC, 16 mug/ml). Vaborbactam showed no antibacterial activity alone (all MICs, >64 mug/ml). Meropenem-vaborbactam appears to be a good candidate for further development and it could increase the options for treatment of serious infections caused by carbapenemase-producing pathogens.

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