In Vitro Activity of Meropenem-Vaborbactam Against Isolates of KPC-producing Enterobacteriaceae Collected Worldwide in 2014-2015

In Vitro Activity of Meropenem-Vaborbactam Against Isolates of KPC-producing Enterobacteriaceae Collected Worldwide in 2014-2015

M. Hackel, R. Badal, D.  Sahm

IHMA, Inc. Schaumburg, IL, USA

Background: Vaborbactam (formerly RPX7009) is a novel β-lactamase inhibitor with potent activity against class A carbapenemases such as KPC. The meropenem-vaborbactam (MEM-VAB) combination is in Phase 3 clinical trials. The activity of MEM-VAB and comparator agents was evaluated against a recent global collection of KPC-producing Enterobacteriaceae.

Methods:

MICs of MEM alone or with VAB at fixed 8 µg/ml, tigecycline (TCG), polymyxin B (PMB), and gentamicin (GEN) were determined against 991 KPC-producing, OXA-48- and MBL-negative isolates following CLSI guidelines.  The study collection was comprised of 11 species and six KPC variants collected in 2014-2015 in Europe, North and Latin Americas, and Asia/South Pacific.

Results:

Cumulative % inhibited by MEM alone and with VAB are shown in the table below, with MIC₉₀ values boxed and shaded.

		MIC (µg/ml)
Organism (n)		≤0.03	0.06	0.12	0.25	0.5	1	2	4	8	16	32	>32
Enterobacteriaceae	MEM	0	0	0	0	0	0	4.1	11.9	24.5	39.6	53.7	100
(991)	MEM-VAB	46.3	51.9	57.7	71.3	85.4	93.4	97.4	98.9	99.5	99.7	99.7	100
Klebsiella spp.	MEM	0	0	0	0	0	0	2.3	8.1	20.3	35.0	49.6	100
(897)	MEM-VAB	43.3	48.5	54.0	68.8	84.2	92.9	97.1	98.8	99.4	99.7	100	100
E. coli	MEM	0	0	0	0	0	0	25.7	65.7	85.7	94.3	100	100
(35)	MEM-VAB	97.1	97.1	100	100	100	100	100	100	100	100	100	100
Enterobacter spp.	MEM	0	0	0	0	0	0	27.6	44.8	55.2	86.2	89.7	100
(29)	MEM-VAB	75.9	86.2	100	100	100	100	100	100	100	100	100	100

MIC₅₀/₉₀ for all strains for TGC, PMB, and GEN were 1/2, 0.5/16 and 1/>64 ug/ml, respectively.

Conclusion:

MEM-VAB showed excellent in vitro activity against KPC-producing Enterobacteriaceae, lowering the meropenem MIC₅₀ and MIC₉₀ from 32 to 0.06 µg/ml, and >32 to 1 µg/ml, respectively. There were no significant differences in activity between species or KPC variant type.  VAB restores the in vitro activity of MEM against this large collection of recent clinical isolates of KPC-producing Enterobacteriaceae.