Study on the optimization of administration regimen of vancomycin in critical patients

Abstract

To observe the changing characteristics of pharmacokinetic and pharmacodynamic (PK-PD) parameters of vancomycin in critical patients under different drug regimens and to further explore the influencing factors. The clinical data of patients who treated with vancomycin and recorded by steady-state through concentration (Cmin) admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2011 to December 2018 were analyzed retrospectively. The patients were divided into three groups according to the dosing interval (groups of q12 h, q8 h and q6 h respectively) and Cmin was collected. The serum concentration of vancomycin before (0 hour) and 1, 2, 4, 6, 8, 12 and 24 hours after administration were estimated by JPKD Ver 3.1. Area under the curve (AUC0-24 h) was estimated by trapezoidal area method. Minimum inhibitory concentration (MIC) of pathogenic microorganisms in the same period was retrieved, thus AUC0-24 h/MIC was calculated. 285 patients with 529 records of Cmin were enrolled in the study, including 375 data in q12 h group, 121 data in q8 h group and 33 data in q6 h group. After unifying daily dose by JPKD Ver 3.1, the Cmin (10-20 mg/L) reaching rate of q12 h group, q8 h group, q6 h group were 35.7%, 43.8% and 60.6%, respectively, while only q12 h group was statistically significant compared with q6 h group (P < 0.01). q6 h group and q8 h group showed higher Cmin than q12 h group (mg/L: 13.8±5.2, 13.5±7.3 vs. 11.4±7.9, both P < 0.05) and lower peak concentration (Cmax) than q12 h group (mg/L: 19.4±5.3, 21.5±7.3 vs. 23.9±8.1, both P < 0.05). However, there was no significant difference in terms of percentage of PD target (AUC0-24 h/MIC ≥ 400) among the three groups (q12 h group, q8 h group, q6 h group were 38.1%, 41.3%, 45.5%, P > 0.05). Multiple linear regression analysis showed that creatinine clearance (CCr) and vancomycin clearance (CLvancomycin) were the main influencing factors of vancomycin PD parameters such as Cmin and AUC0-24 h/MIC (r values of CCr were -0.391, -0.424, and rvalues of CLvancomycin were -0.673, -0.663, all P < 0.01), and were negatively correlated with age (r values were -0.432 and -0.488, respectively, both P < 0.01). At the same daily dose, Cmin can be increased and Cmax can be decreased by increasing the frequency of vancomycin administration, thus minimize the fluctuation of vancomycin serum concentration, but AUC0-24 h/MIC is not affected. Vancomycin administration regimen in severe patients should be optimized according to CCr, CLvancomycin and age.