Optimizing Polymyxin B Therapy in Critical Care: Pharmacokinetic Insights and Clinical Outcomes in a Retrospective Cohort Study

Carbapenem-resistant Gram-negative bacteria pose significant global health threats due to high infection rates and limited treatment options. Polymyxin B (PMB) has reemerged as a last-line therapy against these pathogens, despite nephrotoxicity and neurotoxicity concerns. However, the precise correlation between PMB exposure and response/toxicity has not been well established. The objective of this study was to assess the impact of polymyxin B pharmacokinetics on clinical outcomes in critically ill patients. This single-center, retrospective study included 146 critically ill patients treated with PMB from January 2020 to July 2023. The primary outcome was 28-day mortality, while secondary outcomes included clinical efficacy, length of hospital and intensive care unit (ICU) stay and new onset acute kidney injury (AKI). The 28-day mortality rate was 43.2%. Multivariable Cox regression analysis showed PMB pharmacokinetic parameters, an area under the concentration–time curve across 24 h at steady state (AUCss, 24 h), C6h, and Cmin were associated with mortality. The receiver operating characteristic (ROC) analysis indicated an AUCss, 24 h cutoff of 81.6 mg·h/l for predicting mortality. AKI occurred in 40.6% of patients. Logistic regression revealed that baseline estimated glomerular filtration rate (eGFR) (adjusted OR 0.979, 95% CI 0.963–0.994, P = 0.007) and PMB treatment duration (adjusted OR 1.101, 95% CI 1.007–1.204, P = 0.034) were independent risk factors for AKI. PMB pharmacokinetics are closely related to patient outcomes. An AUCss, 24 h ≥ 81.6 mg·h/l may reduce mortality. Baseline eGFR and PMB treatment duration are independent risk factors for AKI during PMB therapy.