Influencing Factors of Polymyxin B Exposure and the Correlation Between PK/PD Index and Efficacy in Patients with Multidrug-resistant Gram-negative Bacterial Infections
10.3870/j.issn.1004-0781.2025.03.016
- VernacularTitle:多重耐药革兰阴性菌感染患者多黏菌素B暴露量影响因素及PK/PD参数与疗效相关性
- Author:
Simin ZHOU
1
;
Xuemei LUO
;
Weihong GE
Author Information
1. 中国药科大学南京鼓楼医院药学部,南京 210008;中国药科大学基础医学与临床药学学院,南京 210009
- Publication Type:Journal Article
- Keywords:
Polymyxin B;
Multidrug-resistant Gram-negative bacteria;
Exposure;
Pharmacokinetic/Pharmacodynamic;
Influencing factors
- From:
Herald of Medicine
2025;44(3):428-434
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the factors affecting the exposure of polymyxin B and the correlation between pharmacokinetic/pharmacodynamic(PK/PD)indexes and efficacy in patients with multidrug-resistant Gram-negative bacterial(MDR-GNB)infections.Methods This prospective study was conducted in patients who received polymyxin B to treat MDR-GNB infections in the intensive care unit of Nanjing Drum Tower Hospital,Medical College,Nanjing University from January 2021 to December 2023.Plasma concentrations of polymyxin B were analyzed using a high-performance liquid chromatography-tandem mass spectrometry,and the influencing factors of exposure were investigated.The predictive value of area under the concentration-time curve(AUC24h)and AUC24hto minimum inhibitory concentration ratio for efficacy was determined by the receiver operating characteristic curve.Results The median of AUC24h was 76.11(56.06,96.94)μg·mL-1·h in 96 patients with MDR-GNB infections.Patients in the high-dose group(≥ 150 mg·d-1)were more likely to have higher exposure of polymyxin B than those in the low-dose group(＜150 mg·d-1)(P＜0.05).The exposure in patients with renal replacement therapy was significantly de-creased(P＜0.01).However,increasing the dose in patients receiving renal replacement therapy had no significant difference on exposure.The ROC curve showed AUC24h/MIC was closely correlated with clinical efficacy in patients with MDR-GNB infections(AUCROC=0.724,P＜0.01)and the optimal cut-off value of AUC24h/MIC was 62.1.Subgroup analysis showed that the optimal cut-off values of AUC24h/MIC in patients with and without pulmonary infection were 70.8 and 61.5,respectively.The clinical effi-cacy rate was significantly higher in AUC24 h/MIC≥62.1 group,compared with those in AUC24 h/MIC＜62.1 group(72.88％vs.32.43％,P＜0.01).After treatment,the decreasing trend of inflammation indicators in AUC24 h/MIC≥ 62.1 group was superior to those in AUC24h/MIC＜62.1 group.Conclusion The dose and renal replacement therapy are the significant factors influencing the exposure of polymyxin B.AUC24 h/MIC with the target of 62.1 was the optimal exposure index to predict the efficacy in the treatment of MDR-GNB infections and the optimal threshold of AUC24h/MIC was higher in patients with pulmonary infections than in non-pulmonary patients,so therapeutic drug monitoring is recommended to adjust the AUC24h/MIC index to achieve individual-ized medication.
