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 130 ml/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 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. 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 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, 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 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/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 15 mg/kg every 8 h 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.

The Impact of Augmented Renal Clearance on Vancomycin Pharmacokinetics and Pharmacodynamics in Critically Ill Patients

“…Most of the included articles were observational studies, with 14 being retrospective and 5 prospective. One article [7] reported a combination of retrospective and prospective studies and the remaining article [12] was a randomized clinical trial. The studies included diverse ICU populations, including medical, surgical, neurosurgical, haemorrhagic Most of the included articles were observational studies, with 14 being retrospective and 5 prospective.…”

“…The studies included diverse ICU populations, including medical, surgical, neurosurgical, haemorrhagic Most of the included articles were observational studies, with 14 being retrospective and 5 prospective. One article [7] reported a combination of retrospective and prospective studies and the remaining article [12] was a randomized clinical trial. The studies included diverse ICU populations, including medical, surgical, neurosurgical, haemorrhagic stroke, traumatic brain injury (TBI), and septic patients, conducted in seven countries.…”

“…The main finding was decreased therapeutic concentrations following the increase in CrCl. When targeting a C trough of 10-20 mg/L, the reviewed articles revealed that a significant proportion of patients with a CrCl ≥ 130 mL/min (ranging from 34-100%) experienced subtherapeutic trough vancomycin concentrations (C trough < 10 mg/L) with standard vancomycin doses [7,8,10,12,18,20,[22][23][24][25][26]31]. In a prospective study conducted by Campassi et al that included 363 critically ill patients, ARC was assessed for its impact on serum vancomycin concentrations.…”

“…Moreover, patients with ARC exhibited a lower trend compared to the non-ARC group (232.9 vs. 316 mg.h/L) [24] (Table 1). In a randomized clinical trial conducted by Sahrai et al, two different regimens of vancomycin administration (15 mg/kg every 12 h or 8 h) were compared in ARC patients, revealing that target AUC/MIC was achieved by a higher percentage of the group receiving vancomycin every eight hours compared to every 12 h (82.14% versus 46.42%) [12]. The reviewed studies collectively suggested that the typical dosage was insufficient and that increased dosing or dosing frequency is required to achieve adequate concentration; however, only a few studies provided specific dosing recommendations [12,24,30] (Table 2).…”

“…Antibiotics like vancomycin depend on the magnitude of exposure over time for their antibacterial efficacy [9]. Recent studies have revealed that patients with ARC tend to have lower concentrations of vancomycin and require higher dosages to achieve optimal exposure [10][11][12].…”