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Although overall incidence rates of infections sustained by metallo-\u03b2-lactamase (M\u03b2L)-producers have remained lower than those sustained by other carbapenemase-producers, albeit with substantial geographic differences, a significant increase in the prevalence of M\u03b2L-producers has been observed over the last decade. The recent development of new antimicrobials expanded the armamentarium to counter the challenge of metallo-\u03b2-lactamase (M\u03b2L)-producers. Cefiderocol and aztreonam\/avibactam are already clinically available and recommended by international guidelines. In addition, two new classes of \u03b2-lactam\/ \u03b2-lactamase combinations are under clinical evaluation: (<jats:italic>i<\/jats:italic>) combination of \u03b2-lactam with novel boronic-derived inhibitors (e.g. taniborbactam and xeruborbactam), (<jats:italic>ii<\/jats:italic>) combination of \u03b2-lactam with last generation diazabicyclooctane \u03b2-lactamase inhibitors (e.g. zidebactam and nacubactam), active on most of serine-\u03b2-lactamases but also showing strong intrinsic activity on PBP-2. This review aims to provide up-to-date data on the characteristics, activity and emerging resistance mechanisms of the armamentarium of clinically available or soon-to-be introduced drugs for the treatment of M\u03b2L-producing Gram-negative organisms.<\/jats:p>","DOI":"10.1007\/s10096-025-05080-1","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T18:19:40Z","timestamp":1741630780000},"page":"1041-1068","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-\u03b2-lactamase producers"],"prefix":"10.1007","volume":"44","author":[{"given":"Matteo","family":"Boattini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gaibani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Comini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Cavallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Broccolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"issue":"10325","key":"5080_CR1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","volume":"399","author":"CJL Murray","year":"2022","unstructured":"Murray CJL, Ikuta KS, Sharara F, Swetschinski L, Robles Aguilar G, Gray A et al (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. 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