Model-based Evaluation of the Clinical and Microbiological Efficacy of Vancomycin: A Prospective Study of Chinese Adult In-house Patients. (13th November 2018)

• Record Type: Journal Article
• Authors: Shen, Kai; Yang, Minjie; Fan, Yaxin; Liang, Xiaoyu; Chen, Yuancheng; Wu, Jufang; Yu, Jicheng; Zhang, Huifang; Wang, Ruilan; Zhang, Fengying; Hang, Jingqing; Wen, Xiaoxing; Li, Huayin; Shen, Lihua; Zhang, Zhongwei; Wu, Shengbin; Shen, Bo; Huang, Weifeng; Chang, Chunkang; Shen, Yuqi; Ren, Hong; Yuan, Qing; Song, Xiaolian; Luo, Xuming; Zhang, Hong; Yang, Wanqiu; Yang, Jiansong; Zhang, Jing
• Is Part Of: Clinical infectious diseases. Volume 67(2018)Supplement 2
• Page Start: S256
• Page End: S262
• Publication Date: 2018-11-13
• Subjects: vancomycin -- pharmacokinetics -- pharmacodynamics -- efficacy -- therapeutic drug monitoring; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciy667
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Our aims in this prospective study were to evaluate the correlations between pharmacokinetic/pharmacodynamic (PK/PD) indices and the clinical/microbiological efficacy of vancomycin and to identify an appropriate PK/PD target in the Chinese population to guide vancomycin treatment in the clinic. Methods: Adult patients from 11 hospitals in China with gram-positive infections who received vancomycin therapy for ≥5 days and who were under therapeutic drug monitoring (TDM) were enrolled in this study. A 1-compartment population PK model was established and validated. The correlations between PK/PD indices (Cmin, Cmax, 0–24 hour area under the curve (AUC0-24 ), and AUC0-24 /minimum inhibitory concentration (MIC) and clinical outcomes (clinical efficacy and bacterial eradication) were evaluated. Results: In total, 402 adult Chinese patients were enrolled. Among them, 380 patients were evaluable for PK analysis, and 334 were evaluable for PK/PD analysis. In the final population PK model, creatinine clearance (CLCR ) was the significant covariate on CL (typical value, 3.87 L/hour; between-subject variability (BSV), 12.5%), and age was the significant covariate on volume of distribution (V) (typical value, 45.1 L; BSV, 24.8%). The univariate analysis showed that Cmax, AUC0-24, and AUC0-24 /MIC were significantly different or marginally significantly different (P values were 0.009, 0.0385, and 0.0509, respectively) between microbiological outcome groups with coagulase-negative Staphylococcus infections. However, there were no significant differences ( P > .05) in the above PK parameters by multivariate logistic regression analysis, indicating there was no independently associated factor. Conclusions: No significant correlations were identified between PK/PD indices and the clinical or microbiological efficacy of vancomycin in Chinese patients. The necessity of vancomycin TDM based on trough concentration and the current treatment target of AUC0-24 /MIC ≥400 need to be further evaluated and confirmed in additional prospective studies.