Comparison of Vancomycin Clearance Between Augmented Renal Clearance and Normal Renal Function in Critically Ill Infants: A Population Pharmacokinetics Study

Abstract

Augmented renal clearance presents as super-renal function with enhanced renal perfusion and glomerular hyperfiltration in many critically ill infants. This study was to compare vancomycin clearance (CL) between critically ill infants with augmented renal clearance and with normal renal function and to optimize the vancomycin dosage. Data were retrospectively obtained from infants treated in intensive care units. Population pharmacokinetics analysis was conducted using nonlinear mixed-effects model software. A total of 66 critically ill infants were included: 47 infants with augmented renal clearance and 19 infants with normal renal function. The median doses of vancomycin for infants with augmented renal clearance and with normal renal function were 48 and 47 mg/kg/day (P > .05), respectively. The median CL in infants with augmented renal clearance was increased 1.96-fold compared with infants who had normal renal function (0.98 versus 0.5 L/h, P < .001). Simulations indicated that the recommended dosage of 60, 70, 80, 90, and 100 mg/kg/day would be appropriate in critically ill infants with an estimated glomerular filtration rate (eGFR) of 130-149, 150-169, 170-189, 190-209, and >210 mL/min/1.73 m 2 , respectively. Doses of 70 and 75 mg/kg/day were recommended for infants with augmented renal clearance and gestational ages of 27-32.9 and 33-39 weeks, respectively. Doses of 70, 75, 80, and 90 mg/kg/day were recommended for infants with augmented renal clearance and weights of 2.0-2.9, 3.0-3.9, 4.0-4.9, and 5.0-6.0 kg, respectively. In conclusion, the typical vancomycin dosage is insufficient for critically ill infants with augmented renal clearance. Premature infants and infants of low weight with augmented renal clearance need individualized dosing regimens to obtain an adequate area under the serum concentration time curve over 24 h/minimum inhibitory concentration ratio.

Individualized antibiotic dosage regimens for patients with augmented renal clearance

“…Even at the maximum recommended dose of VCM of 161.9 mL/min/1.73m2 provided to a patient with eGFR, therapeutic efficacy could not be achieved, with consequent treatment failure and a fatal outcome, clearly highlighting the need for early dose adjustment of VCM based on urinary CrCl ( Pata et al, 2021 ). The typical VCM dosage was insufficient and higher doses were also required to achieve adequate exposure in critically ill infants with ARC ( Huang et al, 2022 ). However, patients with higher exposure to vancomycin are more likely to experience toxicity, such as acute kidney injury{ Kim et al, 2023 #3}.…”