Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Abstract

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130ml/min were included in the study. The first group received 15mg/kg of vancomycin every 12h and the second group 15mg/kg every 8h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12h and every 8h groups was 44.04 ± 16.55 and 42.86 ± 11.83years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32ml/min in the every 12h group and 171.78 ± 48.56ml/min in the every 8h group. 46.42% of patients in the every 12h group and 82.14% of patients in the every 8h group attained AUC/MIC of more than 400mg × hr/L. None of the patients in the every 12h group reached more than 15mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15mg/kg every 8h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.