{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:24:48Z","timestamp":1791951888100,"version":"4.3.4"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"Supplement_4","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multi-drug resistant (MDR) Gram-negative bacteria represent a growing threat, with an increasing prevalence of carbapenem-resistant Enterobacterales (CRE) infections, for which treatment options are limited. New treatment combinations composed of a \u03b2-lactam antibiotic plus a potent \u03b2-lactamase inhibitor (BLI) with anti-carbapenemase activity have been developed, including two carbapenem\/BLI combinations that are commercially available\u2014meropenem\/vaborbactam (Vabomere\u00ae in the US, Vaborem\u00ae in Europe; Melinta Therapeutics) and imipenem\/cilastatin\/relebactam (Recarbrio\u00ae; Merck Sharp &amp; Dohme), plus one other (meropenem\/nacubactam) in early clinical development. This review provides a summary of the preclinical evidence supporting the use of carbapenem\/BLI combinations and presents the clinical evidence across a range of MDR Gram-negative infections, with a focus on the use of meropenem\/vaborbactam. All three BLIs have shown in vivo activity against Klebsiella pneumoniae carbapenemase and other class A carbapenemases. In 2019, meropenem\/vaborbactam was listed in the WHO\u2019s list of essential medicines, because of its activity against priority 1 antibiotic-resistant pathogens. Meropenem\/vaborbactam has considerable in vitro and in vivo activity against CRE, and in vitro evidence showing a low potential for resistance at clinically relevant doses. In randomized trials, meropenem\/vaborbactam was non-inferior to piperacillin\/tazobactam in patients with complicated urinary tract infection and more effective than the best-available treatment in patients with serious CRE infections. Meropenem\/vaborbactam is well tolerated and, based on clinical experience, demonstrated lower toxicity compared with the combination regimens that have previously been the standard of care. In conclusion, carbapenem\/BLI combinations represent an important therapeutic strategy in patients with MDR Gram-negative infections.<\/jats:p>","DOI":"10.1093\/jac\/dkab353","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T15:13:33Z","timestamp":1633014813000},"page":"iv38-iv45","source":"Crossref","is-referenced-by-count":40,"title":["The role of new carbapenem combinations in the treatment of multidrug-resistant Gram-negative infections"],"prefix":"10.1093","volume":"76","author":[{"given":"Emilio","family":"Bouza","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology and Infectious Diseases, Hospital Gregorio Mara\u00f1on, Department of Medicine Universidad Complutense, CIBERES, Ciber de Enfermedades Respiratorias, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,21]]},"reference":[{"key":"2021120104000830300_dkab353-B1","year":"2019"},{"key":"2021120104000830300_dkab353-B2","first-page":"6007","article-title":"The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2017\/2018","volume":"18","year":"2020","journal-title":"EFSA Journal"},{"key":"2021120104000830300_dkab353-B3"},{"key":"2021120104000830300_dkab353-B4","doi-asserted-by":"crossref","first-page":"iii2","DOI":"10.1093\/jac\/dky027","article-title":"Treatment of infections caused by multidrug-resistant Gram-negative bacteria: report of the British Society for Antimicrobial Chemotherapy\/Healthcare Infection Society\/British Infection Association Joint Working Party","volume":"73","author":"Hawkey","year":"2018","journal-title":"J Antimicrob 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