{"title":"Optimizing Polymyxin B Therapy in Critical Care: Pharmacokinetic Insights and Clinical Outcomes in a Retrospective Cohort Study.","authors":"Qingyun Peng, Qing Li, Mengru Xiong, Mingze Bi, Linlin Hu, Jie He, Shijia Zhong, Shuai Liu, Haofei Wang, Chen Zhang, Jianfeng Xie, Yingzi Huang","doi":"10.1007/s40121-025-01213-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious Diseases and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40121-025-01213-3","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: 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.
Methods: 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).
Results: 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.
Conclusions: 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.
期刊介绍:
Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.