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This versatile Gram-negative bacterium is notorious for its highly plastic genome, which enables the rapid emergence and dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, severely limiting the available treatment options. The genetic flexibility of\n                    <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                    underpins its arsenal of molecular mechanisms, enabling it to resist a range of antibiotics, from traditional agents to the latest therapeutic advancements available. With the progress made in treatments against\n                    <jats:italic toggle=\"yes\">Acinetobacter<\/jats:italic>\n                    infections and various drugs undergoing clinical trials, the effectiveness of these treatments is often outpaced by the pathogen\u2019s swift evolution of resistance, resulting in alarmingly high rates of treatment failure. In this systematic review of literature spanning 2004\u20132024, we highlight the high mortality rates associated with infections caused by XDR strains and carbapenem-resistant\n                    <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                    (CRAB). This review provides a comprehensive examination of the resistance mechanisms deployed by\n                    <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                    , encompassing both conventional antibiotics and novel agents used in global healthcare settings. In addition, we discuss emerging druggable targets and the inherent challenges in their development, offering strategic insights into next-generation therapeutic programs. A deep profound understanding of the pathogen\u2019s molecular defenses is essential to guide the design of innovative therapies aimed at mitigating the escalating threat posed by\n                    <jats:italic toggle=\"yes\">A. baumannii<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/cmr.00279-24","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:23:58Z","timestamp":1754915038000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Drug-resistant\n                    <i>Acinetobacter baumannii<\/i>\n                    : mortality, emerging treatments, and future pharmacological targets for a WHO priority pathogen"],"prefix":"10.1128","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-1469","authenticated-orcid":true,"given":"Vineet","family":"Dubey","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xs57h96","id-type":"ROR","asserted-by":"publisher"}],"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1183-3262","authenticated-orcid":true,"given":"Nada","family":"Reza","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xs57h96","id-type":"ROR","asserted-by":"publisher"}],"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-878X","authenticated-orcid":false,"given":"William","family":"Hope","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xs57h96","id-type":"ROR","asserted-by":"publisher"}],"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.95.5.1520-1541.1968"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00058-07"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/500202"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020007"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00068"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1332108"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp427"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41426-018-0038-9"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02207-23"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics9030119"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1196774"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00858-6"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2542-5196(23)00026-8"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.2144\/fsoa-2018-0127"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad109"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics8030105"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio841"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00736-15"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12199-015-0468-0"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2021.08.001"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11131946"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208468"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.716627"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1053968"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12121749"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11092174"},{"key":"e_1_3_4_29_2","unstructured":"Western Illinois University. 2024. 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