Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
Crit Care. 2023 Apr 28;27(1):164. doi: 10.1186/s13054-023-04448-z.
Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens.
Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy.
A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUC/MIC (AOR = 0.97, 95% CI 0.95-0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97-0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11-0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUC/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial.
For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.
多粘菌素 B 是治疗碳青霉烯类耐药菌（CRO）医院获得性肺炎的一线治疗药物。然而，其药代动力学/药效学（PK/PD）关系的临床数据有限。本研究旨在探讨多粘菌素 B 暴露与治疗危重症患者 CRO 肺炎疗效之间的关系，并优化个体给药方案。
纳入接受多粘菌素 B 治疗 CRO 肺炎的患者。采用经验证的高效液相色谱-串联质谱法测定血样。采用 Phoenix NLME 软件进行群体 PK 分析和蒙特卡罗模拟。采用逻辑回归分析和受试者工作特征（ROC）曲线确定多粘菌素 B 疗效的显著预测因子和 PK/PD 指标。
共纳入 105 例患者，基于 295 个血浆浓度建立了群体 PK 模型。AUC/MIC（AOR=0.97，95%CI 0.95-0.99，p=0.009）、日剂量（AOR=0.98，95%CI 0.97-0.99，p=0.028）和吸入多粘菌素 B 联合治疗（AOR=0.32，95%CI 0.11-0.94，p=0.039）是多粘菌素 B 疗效的独立危险因素。ROC 曲线显示 AUC/MIC 是预测多粘菌素 B 治疗 CRO 医院获得性肺炎的最具预测性 PK/PD 指标，联合另一种抗菌药物治疗时的最佳截断值为 66.9。基于模型的模拟表明，在 MIC 值≤0.5 和 1mg/L 时，维持日剂量 75 和 100mg Q12h 可分别达到该临床目标的≥90%PTA。对于无法通过静脉给药达到目标浓度的患者，辅助吸入多粘菌素 B 可能有益。
对于 CRO 肺炎，推荐每日剂量 75 和 100mg Q12h 以获得临床疗效。对于无法通过静脉给药达到目标浓度的患者，吸入多粘菌素 B 有益。
Zotero 插件
