[Clinical study of vancomycin for appropriate dosing in severe infective patients with augmented renal clearance]

To explore the impact of augmented renal clearance (ARC) on vancomycin pharmacokinetic target attainment in severe infective patients, and to analyze the initial dose of vancomycin based on the measured 12-hour urinary creatinine clearance (12 h-CL_CR).

A retrospective observational study was conducted. The patients with severe infection, who receiving vancomycin empiric or targeted therapy, admitted to intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from February 2013 to December 2017 were enrolled. All patients were treated with vancomycin intravenously by intermittent bolus every 6-12 hours. After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CL_CR was calculated. ARC was defined as 12 h-CL_CR > 130 mL×min^-1×1.73 m^-2. According to 12 h-CL_CR before treatment, the patients were divided into ARC group and non-ARC group. The basic renal function of the patients was monitored, and the dosage of vancomycin and the dosage of vancomycin when the blood concentration reached the target were recorded. The correlations between 12 h-CL_CR and the dosage of vancomycin when the blood concentration reached the target as well as the blood concentration of vancomycin were analyzed by Spearman correlation analysis. Dosage stratification analysis was carried out according to different 12 h-CL_CR. The predictive value of 12 h-CL_CR for vancomycin dosage when the blood concentration reached the target was evaluated by using the receiver operator characteristic curve (ROC).

Data was provided from a total of 135 patients with severe infection, in which 102 patients met the inclusion criteria. The patients with vancomycin treatment duration less than 72 hours, chronic kidney disease V phase, vancomycin treatment before entering ICU and those with incomplete data were excluded. The mean 12 h-CL_CR was (114.31±73.38) mL×min^-1×1.73 m^-2. The 12 h-CL_CR in ARC group (n = 44, 43.14%) was significantly higher than that in non-ARC group (n = 58, 56.86%) (mL×min^-1×1.73 m^-2: 179.37±59.04 vs. 65.95±35.71, P < 0.01). Target Cmin of vancomycin was achieved in 50.98% of patients (52/102), the target rate in ARC group was significantly lower than that in non-ARC group [29.55% (13/44) vs. 67.24% (39/58), P < 0.01], and the Cmin of vancomycin in ARC group was significantly lower than that in non-ARC group (mg/L: 10.98±6.09 vs. 14.67±6.20, P < 0.01). Spearman correlation analysis showed that there was a significantly negative correlation between 12 h-CL_CR and initial Cmin of vancomycin (n = 102, r = -0.436, P < 0.001), but a positive correlation was found between 12 h-CL_CR and vancomycin dosage when the blood concentration reached the target (n = 52, r = 0.275, P = 0.048). The patients with ARC need higher dosage for blood concentration reaching the target than those without ARC (mg×kg^-1×d^-1: 42.47±13.17 vs. 31.53±14.43, P < 0.01). According to 12 h-CL_CR, the patients with initial treatment reaching the target were divided into five subgroups, < 40, 40-70, 71-100, 101-130 and > 130 mL×min^-1×1.73 m^-2. The results showed that as 12 h-CL_CR increased, the attained dosage of vancomycin was also increased correspondingly. ROC curve analysis showed that when 12 h-CL_CR≥69.83 mL×min^-1×1.73 m^-2, the attained dose of vancomycin when the blood concentration reached the target was greater than conventional dosage of 30 mg×kg^-1×d^-1.

Patients with ARC have low concentrations of vancomycin and often fail to achieve therapeutic target. The initial dose of vancomycin can be selected according to 12 h-CL_CR, the higher the 12 h-CL_CR, the more the dosage of vancomycin is. When 12 h-CL_CR is greater than or equal to 69.83 mL×min^-1×1.73 m^-2, the dosage of vancomycin should be higher than the conventional dosage.