{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:54:50Z","timestamp":1791924890074,"version":"4.3.4"},"reference-count":148,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":140,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Microbiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010Lactam antibiotics have long served as a cornerstone for treating bacterial infections. However, their widespread and often indiscriminate use has fueled the emergence of multidrug\u2010resistant Gram\u2010negative pathogens, primarily through the production and dissemination of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactamase enzymes. The proliferation of these enzymes represents a critical threat to global public health, compounding therapeutic challenges and escalating healthcare costs. As the efficacy of conventional treatments diminishes, reliance on last\u2010resort agents like carbapenems and colistin has increased, in turn accelerating resistance to these precious final\u2010line options. To address this escalating crisis, the strategic combination of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactam antibiotics with\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactamase inhibitors (BLIs) has emerged as a vital therapeutic approach, restoring the activity of\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactams by inactivating the resistance enzymes. Since the introduction of clavulanic acid, significant progress has been made in expanding the BLI arsenal. This review provides a comprehensive analysis of the current landscape of novel BLIs that have been approved or are in advanced clinical development, delving into their distinct mechanisms of action, spectra of activity against Ambler molecular classes (A, B, C, and D), and evolving clinical applications. While early inhibitors primarily targeted serine\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactamases (SBLs), recent advancements have introduced agents with expanded profiles, including those effective against some Class D carbapenemases. A paramount, ongoing challenge remains the development of effective inhibitors against metallo\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010lactamases (MBLs), though promising candidates like taniborbactam and xeruborbactam are now in clinical development. This review synthesizes the current knowledge on these innovative inhibitors, from recently approved combinations like ceftazidime\/avibactam and cefepime\/enmetazobactam to those in advanced clinical trials, and critically examines the associated therapeutic challenges, including the emergence of resistance. By integrating mechanistic insights with clinical perspectives, this article is aimed at informing the ongoing battle against antimicrobial resistance and guiding the future development of life\u2010saving therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1155\/ijm\/4479031","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:10:16Z","timestamp":1779361816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Review of\n                    <i>\u03b2<\/i>\n                    \u2010Lactamase Inhibitors in Clinical Use and Development: Mechanisms, Spectrum, and Therapeutic Applications"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6465-9449","authenticated-orcid":false,"given":"Mohammad Javad 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