WITHDRAWN: Clinical Efficacy and Pharmacokinetics/pharmacodynamics Analysis of Intravenous Polymyxin B for Critically Ill Patients with Sepsis

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.