WITHDRAWN: Clinical efficacy and pharmacokinetics/pharmacodynamics analysis of intravenous polymyxin B for critically ill patients with sepsis

2026 · doi:10.21203/rs.3.rs-8434801/v1
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Abstract

Abstract Objectives To investigate the relationship between intravenous polymyxin B (PMB) plasma exposure and clinical outcome in septic patients, and to determine the pharmacokinetics (PK) target. Patients and Methods: This single-center, observational study enrolled septic patients who received PMB therapy between July 2021 and July 2025. The primary clinical outcome was the clinical success rate. The secondary outcomes included 28-day all-cause mortality, 90-day survival time, bacterial clearance, ventilator-free days, ICU-free days and hospital-free days. The AUC ss,0−12h and C ss, avg were analyzed to identify their associations with clinical outcomes, and cut-off value were determined by receiver-operating characteristic (ROC) curves. Monte Carlo simulations were used to recommend initial dosing regimens based on weights and use of continuous renal replacement therapy (CRRT). Results A total of 82 septic patients were included. The clinical success rate was 37.8% with AUC ss, 0−12h cut-off value of 27.10 mg·h/L (C ss, avg 2.26 mg/L). In CRRT subgroup, the loading dose was a protective factor of 90-day survival time. The pneumonia subgroup had a success rate of 46.15%, with an AUC ss, 0–12h cut-off value of 25.47 mg·h/L. For non-CRRT patients weighing 40–80 kg, a 2.5 mg/kg loading dose followed by 1.5 mg/kg every 12 hours achieves a probability of target attainment (PTA) ≥ 90%; For CRRT patients, only patients weighing 40 kg achieved the PK target with a high-dose regimen. Conclusions For septic patients, PMB exposure is associated with clinical efficacy. Maintaining an AUC ss, 0−12h > 27.10 mg·h/L (C ss, avg of 2.26 mg/L) enhances clinical success. This study provides evidence for PMB therapeutic drug monitoring and initial dosing strategies.
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Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author. Editorial notes are used to provide important context regarding the topic of a preprint or to alert readers to potential issues concerning that preprint or a downstream publication associated with it. For more information on editorial notes, see our Editorial Policies . Abstract The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author. Full Text The authors have withdrawn this preprint from Research Square. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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