优化多粘菌素B治疗危重症:回顾性队列研究的药代动力学见解和临床结果。

IF 5.3 3区 医学 Q1 INFECTIOUS DISEASES
Qingyun Peng, Qing Li, Mengru Xiong, Mingze Bi, Linlin Hu, Jie He, Shijia Zhong, Shuai Liu, Haofei Wang, Chen Zhang, Jianfeng Xie, Yingzi Huang
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引用次数: 0

摘要

碳青霉烯耐药革兰氏阴性菌由于高感染率和有限的治疗选择,对全球健康构成重大威胁。多粘菌素B (PMB)已重新出现作为最后一线治疗这些病原体,尽管肾毒性和神经毒性的担忧。然而,PMB暴露与反应/毒性之间的确切关系尚未得到很好的确定。本研究的目的是评估多粘菌素B药代动力学对危重患者临床结局的影响。方法:本研究为单中心回顾性研究,纳入2020年1月至2023年7月期间接受PMB治疗的146例危重患者。主要终点是28天死亡率,次要终点包括临床疗效、住院时间和重症监护病房(ICU)住院时间以及新发急性肾损伤(AKI)。结果:28天死亡率为43.2%。多变量Cox回归分析显示,PMB药代动力学参数、稳态24 h浓度-时间曲线下面积(AUCss, 24 h)、C6h、Cmin与死亡率相关。受试者工作特征(ROC)分析显示,预测死亡率的auss为81.6 mg·h/l, 24 h临界值为81.6 mg·h/l。40.6%的患者发生AKI。Logistic回归显示基线肾小球滤过率(eGFR)(校正OR 0.979, 95% CI 0.963-0.994, P = 0.007)和PMB治疗时间(校正OR 1.101, 95% CI 1.007-1.204, P = 0.034)是AKI的独立危险因素。结论:PMB药代动力学与患者预后密切相关。24 h≥81.6 mg·h/l可降低死亡率。基线eGFR和PMB治疗时间是PMB治疗期间AKI的独立危险因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing Polymyxin B Therapy in Critical Care: Pharmacokinetic Insights and Clinical Outcomes in a Retrospective Cohort Study.

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.

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来源期刊
Infectious Diseases and Therapy
Infectious Diseases and Therapy Medicine-Microbiology (medical)
CiteScore
8.60
自引率
1.90%
发文量
136
审稿时长
6 weeks
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.
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