{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:26Z","timestamp":1787027546241,"version":"build-2736575974"},"reference-count":209,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>The global spread of multidrug-resistant (MDR) Gram-negative pathogens has significantly narrowed therapeutic options for serious infections. MDR organisms frequently harbor multiple resistance mechanisms, such as \u03b2-lactamases and non-\u03b2-lactam determinants, which limit the activity of many \u03b2-lactam\/\u03b2-lactamase inhibitor combinations and complicate the clinical utility of newer agents such as cefiderocol and aztreonam\u2013avibactam. These challenges highlight the need for mechanistically distinct, non-\u03b2-lactam therapies capable of maintaining activity in MDR settings. Eravacycline is a fully synthetic fluorocycline antibiotic that inhibits bacterial protein synthesis through high-affinity binding to the 30S ribosomal subunit, a mechanism unaffected by \u03b2-lactamase-mediated resistance. Structural modifications at key positions confer stability against common tetracycline resistance mechanisms, including efflux pumps and ribosomal protection proteins. In vitro surveillance studies consistently demonstrate potent activity against a broad range of MDR Gram-negative pathogens, notably carbapenem-resistant Enterobacterales and isolates harboring metallo-\u03b2-lactamases. The clinical efficacy and safety of eravacycline have been established in pivotal Phase 3 trials for complicated intra-abdominal infections. Although highly resistant phenotypes were underrepresented in these trials, emerging real-world data describe off-label use in MDR Gram-negative infections, often as salvage or step-down therapy. These experiences suggest acceptable clinical outcomes and favorable tolerability in complex, high-risk patients. This review synthesizes mechanistic, microbiologic, pharmacologic, and clinical evidence supporting eravacycline\u2019s potential role in the management of MDR Gram-negative infections.<\/jats:p>","DOI":"10.3390\/antibiotics15050503","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:53:10Z","timestamp":1779191590000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond \u03b2-Lactams: Defining the Role of Eravacycline in Multidrug-Resistant and Metallo-\u03b2-Lactamase-Producing Infections"],"prefix":"10.3390","volume":"15","author":[{"given":"Jacob M.","family":"Keck","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marino, A., Maniaci, A., Lentini, M., Ronsivalle, S., Nunnari, G., Cocuzza, S., Parisi, F.M., Cacopardo, B., Lavalle, S., and La Via, L. 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