{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:44:39Z","timestamp":1791531879946,"version":"4.3.4"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,11,1]],"date-time":"2017-11-01T00:00:00Z","timestamp":1509494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"crossref","award":["HHSO100201400002C"],"award-info":[{"award-number":["HHSO100201400002C"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore. The spectrum of beta-lactamase inhibition by vaborbactam and the impact of bacterial efflux and permeability on its activity were determined using a panel of strains with beta-lactamases cloned from various classes and a panel of\n                    <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n                    carbapenemase 3 (KPC-3)-producing isogenic strains with various combinations of efflux and porin mutations. Vaborbactam is a potent inhibitor of class A carbapenemases, such as KPC, as well as an inhibitor of other class A (CTX-M, SHV, TEM) and class C (P99, MIR, FOX) beta-lactamases. Vaborbactam does not inhibit class D or class B carbapenemases. When combined with meropenem, vaborbactam had the highest potency compared to the potencies of vaborbactam in combination with other antibiotics against strains producing the KPC beta-lactamase. Consistent with broad-spectrum beta-lactamase inhibition, vaborbactam reduced the meropenem MICs for engineered isogenic strains of\n                    <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n                    with increased meropenem MICs due to a combination of extended-spectrum beta-lactamase production, class C beta-lactamase production, and reduced permeability due to porin mutations. Vaborbactam crosses the outer membrane of\n                    <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n                    using both OmpK35 and OmpK36, but OmpK36 is the preferred porin. Efflux by the multidrug resistance efflux pump AcrAB-TolC had a minimal impact on vaborbactam activity. Investigation of the vaborbactam concentration necessary for restoration of meropenem potency showed that vaborbactam at 8 \u03bcg\/ml results in meropenem MICs of \u22642 \u03bcg\/ml in the most resistant engineered strains containing multiple mutations. Vaborbactam is a highly active beta-lactamase inhibitor that restores the activity of meropenem and other beta-lactam antibiotics in beta-lactamase-producing bacteria, particularly KPC-producing carbapenem-resistant\n                    <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/aac.01443-17","type":"journal-article","created":{"date-parts":[[2017,8,28]],"date-time":"2017-08-28T20:30:26Z","timestamp":1503952226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":344,"title":["Vaborbactam: Spectrum of Beta-Lactamase Inhibition and Impact of Resistance Mechanisms on Activity in Enterobacteriaceae"],"prefix":"10.1128","volume":"61","author":[{"given":"Olga","family":"Lomovskaya","sequence":"first","affiliation":[{"name":"The Medicines Company, San Diego, California, 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