{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:02:36Z","timestamp":1781841756653,"version":"3.54.5"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2019BC025"],"award-info":[{"award-number":["ZR2019BC025"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Amikacin and polymyxins as monotherapies are ineffective against multidrug-resistant <jats:italic>Acinetobacter baumannii<\/jats:italic> at the clinical dose. When polymyxins, aminoglycosides, and sulbactam are co-administered, the combinations exhibit <jats:italic>in vitro<\/jats:italic> synergistic activities. The minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in 11 and 5 clinical resistant isolates of <jats:italic>A. baumannii<\/jats:italic> harboring OXA-23, respectively, in order to derive the fraction of time over the 24-h wherein the free drug concentration was within the mutant selection window (<jats:italic>f<\/jats:italic>T<jats:sub>MSW<\/jats:sub>) and the fraction of time that the free drug concentration was above the MPC (<jats:italic>f<\/jats:italic>T<jats:sub>&amp;gt;MPC<\/jats:sub>) from simulated pharmacokinetic profiles. The combination of these three antibiotics can confer susceptibility in multi-drug resistant <jats:italic>A. baumannii<\/jats:italic> and reduce the opportunity for bacteria to develop further resistance. Clinical intravenous dosing regimens of amikacin, polymyxin-B, and sulbactam were predicted to optimize <jats:italic>f<\/jats:italic>T<jats:sub>MSW<\/jats:sub> and <jats:italic>f<\/jats:italic>T<jats:sub>&amp;gt;MPC<\/jats:sub> from drug exposures in the blood. Mean <jats:italic>f<\/jats:italic>T<jats:sub>&amp;gt;MPC<\/jats:sub> were\u2009\u2265\u200960% and\u2009\u2265\u200980% for amikacin and polymyxin-B, whereas mean <jats:italic>f<\/jats:italic>T<jats:sub>MSW<\/jats:sub> was reduced to &amp;lt;30% and\u2009&amp;lt;15%, respectively, in the triple antibiotic combination. Due to the low free drug concentration of amikacin and polymyxin-B simulated in the epithelial lining fluid, the two predicted pharmacodynamic parameters in the lung after intravenous administration were not optimal even in the combination therapy setting.<\/jats:p>","DOI":"10.3389\/fmicb.2022.1013939","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T14:51:26Z","timestamp":1666277486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistant Acinetobacter baumannii"],"prefix":"10.3389","volume":"13","author":[{"given":"Shixing","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Diao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias M.","family":"Heinrichs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederico S.","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherwin K. 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