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 (C-min, C-max, 0-24 hour area under the curve (AUC(0-24)), and AUC(0-24)/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 C-max, AUC(0-24), and AUC(0-24)/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 AUC(0-24)/MIC >= 400 need to be further evaluated and confirmed in additional prospective studies.
[1]Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai, Peoples R China.
[2]Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai, Peoples R China.
[3]Natl Hlth & Family Planning Commiss Peoples Repub, Key Lab Clin Pharmacol Antibiot, Beijing, Peoples R China.
[4]Fudan Univ, Dept Crit Care Med, Shanghai Gen Hosp, Shanghai, Peoples R China.
[5]Tongji Univ, Putuo Hosp, Dept Respirat, Shanghai, Peoples R China.
[6]Fudan Univ, Dept Respirat, Zhongshan Hosp, Shanghai, Peoples R China.
[7]Fudan Univ, Intens Care Unit, Shanghai Tumor Hosp, Shanghai, Peoples R China.
[8]Shanghai Jiao Tong Univ, Dept Nephrol, Shanghai Peoples Hosp 9, Shanghai, Peoples R China.
[9]Shanghai Jiao Tong Univ, Dept Crit Care Med, Shanghai Peoples Hosp 6, Shanghai, Peoples R China.
[10]Shanghai Jiao Tong Univ, Dept Hematol, Shanghai Peoples Hosp 6, Shanghai, Peoples R China.
[11]Shanghai Jiao Tong Univ, Dept Nephrol, Ruijin Hosp, Shanghai, Peoples R China.
[12]Tongji Univ, Shanghai Hosp 10, Dept Respirat, Shanghai, Peoples R China.
[13]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Respirat, Shanghai, Peoples R China.
[14]Tongji Univ, Dept Pharm, Tongji Hosp, Shanghai, Peoples R China.
[15]Mosim Co Ltd, Shanghai, Peoples R China.
(8.0+极速模式)