{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:46Z","timestamp":1787026306308,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to predict and evaluate the efficacy of various polymyxin B dosing regimens for Gram-negative bacteremia using Monte Carlo simulation, with a specific focus on assessing the efficacy in patients receiving continuous renal replacement therapy (CRRT). The goal was to optimize clinical dosing regimens and guide rational polymyxin B use in practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 1,939 Gram-negative bacterial strains were analyzed, collected between April 2019 and December 2021 through the China Bloodstream Gram-negative Pathogens Antimicrobial Resistance and Virulence Surveillance Network (CARVIS-NET). Pharmacokinetic parameters of polymyxin B from existing literature were used to conduct a Monte Carlo simulation based on pharmacokinetic\/pharmacodynamic (PK\/PD) theory. The probability of target attainment (PTA) and cumulative fraction of response (CFR) were evaluated across various dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The main pathogens of Gram-negative bacteremia were\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      ,\n                      <jats:italic>Klebsiella pneumoniae, Pseudomonas aeruginosa<\/jats:italic>\n                      , and\n                      <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                      , all of which demonstrated high susceptibility to polymyxin B. For pathogens with a minimum inhibitory concentration (MIC) \u22641 mg\/L, all regimens achieved PTA &amp;gt;90%. However, when the MIC increased to 2 mg\/L, the PTA for the 500,000 IU q12h regimen decreased to 77.53%, and at an MIC of 4 mg\/L, none of the dosing regimens achieved a PTA &amp;gt;90%. For\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      with MIC \u22640.5 mg\/L, all regimens demonstrated effectiveness. However, at MIC \u22651 mg\/L, significant declines in PTA were observed, with the 500,000 IU q12h and 1.25 mg\/kg q12h regimens yielding suboptimal outcomes. In CRRT patients, PTA values declined further, particularly against\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      , raising concerns about potential treatment failure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Polymyxin B demonstrates high efficacy for Gram-negative bacteremia with MIC \u22641 mg\/L. However, efficacy diminishes as MIC increases, particularly for\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      , where 500,000 IU q12h and 1.25 mg\/kg q12h regimens may result in suboptimal outcomes. For CRRT patients with\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      bacteremia, therapeutic drug monitoring and dose adjustments are crucial to mitigate treatment failure risks.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1533177","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T02:33:05Z","timestamp":1740537185000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Monte Carlo simulation to optimize polymyxin B dosing regimens for the treatment of Gram-negative bacteremia"],"prefix":"10.3389","volume":"15","author":[{"given":"Yingying","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1093\/jac\/dkq285","article-title":"The impact of polymyxin B dosage on in-hospital mortality of patients treated with this antibiotic","volume":"65","author":"Elias","year":"2010","journal-title":"J.\u00a0Antimicrobial Chemotherapy."},{"key":"B2","article-title":"Implementation and use of the 2022 revised Polymyxin Breakpoints","year":"2022"},{"key":"B3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.jgar.2020.12.026","article-title":"Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence","volume":"24","author":"Falagas","year":"2021","journal-title":"J. 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