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As existing antibiotics lose efficacy against <jats:italic>Acinetobacter<\/jats:italic> isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of <jats:italic>A. baumannii<\/jats:italic>: <jats:italic>A. baumannii<\/jats:italic> 5075, known for its extensive drug resistance, and <jats:italic>A. baumannii<\/jats:italic> QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of <jats:italic>A. baumannii<\/jats:italic> isolates, with IC<jats:sub>50<\/jats:sub>s\u2009\u2264\u200948\u00a0\u00b5M for <jats:italic>A. baumannii<\/jats:italic> QS17-1084 and IC<jats:sub>50<\/jats:sub>s\u2009\u2264\u200917\u00a0\u00b5M for <jats:italic>A. baumannii<\/jats:italic> 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against <jats:italic>A. baumannii<\/jats:italic> QS17-1084 and that of MUT056399 and eravacycline against <jats:italic>A. baumannii<\/jats:italic> 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both <jats:italic>A. baumannii<\/jats:italic> strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant <jats:italic>A. baumannii<\/jats:italic>. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.<\/jats:p>","DOI":"10.1038\/s41598-024-72603-9","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T14:07:09Z","timestamp":1726668429000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii"],"prefix":"10.1038","volume":"14","author":[{"given":"Nonlawat","family":"Boonyalai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dutsadee","family":"Peerapongpaisarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatchadaporn","family":"Thamnurak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilawan","family":"Oransathid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nantanat","family":"Wongpatcharamongkol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wirote","family":"Oransathid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woradee","family":"Lurchachaiwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Griesenbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman C.","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samandra T.","family":"Demons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattaya","family":"Ruamsap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Vesely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"72603_CR1","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1128\/CMR.00058-07","volume":"21","author":"AY Peleg","year":"2008","unstructured":"Peleg, A. 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