{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:52:30Z","timestamp":1790794350392,"version":"4.1.0"},"reference-count":171,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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>Antimicrobial resistance (AMR) is a leading global cause of death, with recent World Health Organization (WHO) data revealing that one in six laboratory-confirmed bacterial infections shows resistance to at least one antibiotic treatment. This review comprehensively analyzes the AMR landscape in 2026, detailing its evolution, mechanisms, and the innovative strategies being deployed to combat it. Driven by Darwinian selection and accelerated by factors like antibiotic overuse during the Coronavirus Disease 2019 (COVID-19) pandemic (predominantly in hospitalized patients with suspected bacterial co-infection), AMR is propelled by a diverse molecular arsenal in bacteria. Key mechanisms include enzymatic drug inactivation (e.g., the diversifying \u03b2-lactamase superfamily), target site modification (e.g., mcr genes conferring colistin resistance), efflux pumps, and biofilm formation. The rapid global spread of these traits is facilitated by a dynamic \u201cmobilome\u201d, a network of plasmids and transposons that shuttle resistance genes between species. This crisis has sparked a major scientific mobilization. Advances include the discovery of novel antibiotic scaffolds like lariocidin and the regulatory approval of critical new antibiotic\/inhibitor combinations such as sulbactam\/durlobactam and aztreonam\/avibactam, which target highly resistant Gram-negative bacteria. Moreover, the first-in-class antibiotic gepotidacin offers a new option for urinary tract infections. Beyond traditional drugs, the pipeline is diversifying to include phage therapy, antivirulence strategies, and artificial intelligence-guided drug discovery. This diversification is critical as it helps preserve the effectiveness of existing Medically Important Antimicrobials (MIAs), those deemed essential for human medicine, by providing alternative or adjunctive treatment options. However, scientific innovation alone is insufficient. This review argues that lasting success requires parallel progress in global policy and infrastructure. Strategic priorities beyond 2026 must include finalizing and funding updated global action plans, strengthening real-time surveillance and diagnostic capacity, especially in low-resource settings, and implementing new economic models to de-risk antibiotic development. Embedding effective antimicrobial stewardship within universal health coverage and pandemic preparedness plans is crucial. Ultimately, defeating AMR demands an unprecedented, coordinated global effort that outpaces the relentless adaptability of bacterial pathogens.<\/jats:p>","DOI":"10.3390\/antibiotics15060564","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:37:26Z","timestamp":1780454246000},"page":"564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Current State of the Fight Against Antimicrobial Resistance: What Are the Different Strategies for Tomorrow?"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1375-4111","authenticated-orcid":false,"given":"Hicham","family":"Wahnou","sequence":"first","affiliation":[{"name":"Sciences and Engineering of Biomedicals, Biophysics and Health Laboratory, Higher Institute of Health Sciences, Hassan First University, Settat 26000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4965-2168","authenticated-orcid":false,"given":"Riad","family":"El Kebbaj","sequence":"additional","affiliation":[{"name":"Sciences and Engineering of Biomedicals, Biophysics and Health Laboratory, Higher Institute of Health Sciences, Hassan First University, Settat 26000, Morocco"},{"name":"Mohammed VI Center for Research & Innovation (CM6RI), Rabat 10112, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-0222","authenticated-orcid":false,"given":"B\u00e9atrice","family":"Demor\u00e9","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Hospital, All\u00e9e du Morvan, 54511 Vand\u0153uvre-l\u00e8s-Nancy, France"},{"name":"INSPIIRE, Inserm, Universit\u00e9 de Lorraine, 54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8816-3001","authenticated-orcid":false,"given":"Youness","family":"Limami","sequence":"additional","affiliation":[{"name":"Sciences and Engineering of Biomedicals, Biophysics and Health Laboratory, Higher Institute of Health Sciences, Hassan First University, Settat 26000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4349-5595","authenticated-orcid":false,"given":"Rapha\u00ebl Emmanuel","family":"Duval","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, 54000 Nancy, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3201\/eid2305.161556","article-title":"The Discovery of Penicillin\u2014New Insights After More Than 75 Years of Clinical Use","volume":"23","author":"Gaynes","year":"2017","journal-title":"Emerg. 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