{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:49:53Z","timestamp":1791924593818,"version":"4.3.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The increasing prevalence of multidrug-resistant (MDR) Gram-negative bacteria and comparatively limited options of antibiotics pose a major threat to public health worldwide. Polymyxin B is the last resort against extensively resistant Gram-negative bacterial infections. However, a large number of Gram-negative bacteria exhibited high-level resistance to Polymyxin B, bringing challenges for antimicrobial chemotherapy. Combination therapies using polymyxins and other antibiotics are recommended to treat multidrug-resistant pathogens. In this study, we selected Gram-negative bacterial strains, including <jats:italic>Klebsiella pneumoniae<\/jats:italic> and <jats:italic>Escherichia coli<\/jats:italic>, to explore whether fusidic acid and polymyxin B have a synergistic killing effect. Through broth microdilution, we observed that minimum inhibitory concentrations (MICs) against polymyxin B in the isolates tested were significantly reduced by the addition of fusidic acid. Notably, chequerboard analysis indicated a synergistic effect between polymyxin B and fusidic acid. In addition, subsequent time-kill experiments showed that the combination of polymyxin B and fusidic acid was more effective than a single drug in killing bacteria. Finally, our investigation utilizing the murine model revealed a higher survival rate in the combination therapy group compared to the monotherapy group. Our research findings provide evidence of the synergistic effect between polymyxin B and fusidic acid. Fusidic acid was shown to increase the sensitivity of multi-drug resistant <jats:italic>E. coli<\/jats:italic> and <jats:italic>K. pneumoniae<\/jats:italic> to polymyxin B, thereby enhancing its bactericidal activity. This study provides new insights into a potential strategy for overcoming polymyxin B resistance, however, further investigations are required to evaluate their feasibility in real clinical settings.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1220683","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T05:12:11Z","timestamp":1697001131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Polymyxin B and fusidic acid, a novel potent synergistic combination against Klebsiella pneumoniae and Escherichia coli isolates with polymyxin B resistance"],"prefix":"10.3389","volume":"14","author":[{"given":"Shuying","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulin","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyou","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunchan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"166","DOI":"10.4067\/S0716-10182016000200006","article-title":"Colistin in the post-antibiotic era","volume":"33","author":"Aguayo","year":"2016","journal-title":"Rev. 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