{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:45Z","timestamp":1786978305976,"version":"build-2736575974"},"reference-count":80,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T00:00:00Z","timestamp":1522195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>\n                    Vaborbactam (VAB; formerly RPX7009) is a novel beta\u2010lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta\u2010lactamases. It has been co\u2010formulated with meropenem to restore its activity against\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug\u2010resistant nonfermenting gram\u2010negative bacilli, notably\n                    <jats:italic>Acinetobacter<\/jats:italic>\n                    spp. and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . The purpose of this article is to review existing data pertaining to the biochemistry, mechanism of action, pharmacokinetics\/pharmacodynamics, in\u00a0vitro activity, and current progress in clinical trials of meropenem and VAB (MV). Phase 1 studies have demonstrated single and multiple doses of VAB up to 2000\u00a0mg, alone or in combination with meropenem 2000\u00a0mg administered as a prolonged infusion over 3\u00a0hours, are well tolerated with an adverse effect profile similar to that of meropenem monotherapy. The available data suggest preexisting resistance among KPC\u2010producing isolates is rare. Strains with elevated MICs have been characterized by multiple resistance determinants including porin defects, increased drug efflux, and increased\n                    <jats:italic>bla<\/jats:italic>\n                    KPC expression. It remains uncertain whether multifactorial resistance will emerge during MV treatment and with more widespread use. Early data are positive for complicated urinary tract infections and MV compared with best available therapy in patients with serious carbapenem\u2010resistant Enterobacteriaciae (CRE) infections. As clinicians contemplate how to incorporate MV into CRE treatment strategies, it will be important to track and understand resistance, discern the role, if any, of combination therapy in enhancing efficacy and\/or preserving activity, and define the specific therapeutic niche of MV among the expanding anti\u2010CRE armamentarium.\n                  <\/jats:p>","DOI":"10.1002\/phar.2092","type":"journal-article","created":{"date-parts":[[2018,2,10]],"date-time":"2018-02-10T11:02:41Z","timestamp":1518260561000},"page":"444-461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem\u2010resistant Enterobacteriaceae"],"prefix":"10.1002","volume":"38","author":[{"given":"Sarah Christina Jane","family":"Jorgensen","sequence":"first","affiliation":[{"name":"Anti\u2010infective Research Laboratory Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0081","authenticated-orcid":false,"given":"Michael Joseph","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti\u2010infective Research Laboratory Eugene Applebaum College of Pharmacy and Health Sciences Wayne State University Detroit Michigan"},{"name":"Division of Infectious Diseases Department of Medicine School of Medicine Wayne State University Detroit Michigan"},{"name":"Department of Pharmacy Services Detroit Medical Center Detroit Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw829"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00001-07"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq108"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02166-13"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365548.2013.861608"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"ofx063","DOI":"10.1093\/ofid\/ofx063","article-title":"Carbapenem\u2010resistant Enterobacteriaceae infections: results from a retrospective series and implications for the design of prospective clinical trials","volume":"2","author":"Alexander EL","year":"2017","journal-title":"Open Forum Infect Dis"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis588"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00883-17"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix783"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw636"},{"issue":"2","key":"e_1_2_8_12_1","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01964-16","article-title":"Ceftazidime\u2010avibactam as salvage therapy for infections caused by carbapenem\u2010resistant organisms","volume":"61","author":"Temkin E","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00449-17"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.01.018"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00127"},{"key":"e_1_2_8_16_1","unstructured":"The Medicines Company.FDA Grants Fast Track Status for Investigational Antibiotic CARBAVANCE\u00ae(meropenem\u2010vaborbactam). 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