Original Research
Monday, November 13, 2023
01:00 PM–02:30 PM
Abstract
Introduction: The physiological changes associated with aging can alter drug disposition, affecting therapeutic target attainment of antibiotics. While vancomycin is frequently used to treat Gram-positive infections in the elderly, current guidelines do not provide specific dosing recommendations for this population.
Research Question or Hypothesis: Would vancomycin initial target attainment be impacted by pharmacokinetic changes in elderly patients?
Study Design: Single center, prospective and longitudinal study.
Methods: Elderly patients (>65 years) with preserved renal function were considered. Vancomycin therapy started with 1g every 12 hours, one-hour infusion. Two steady-state blood samples were collected within the same dosing interval. Pharmacokinetic parameters were estimated using the one-compartment model with first-order kinetics. The therapeutic target was defined as vancomycin 24-hour area under the curve/minimum inhibitory concentration (AUC/MIC) =400 and <600. A linear regression was used to explore the relationship between vancomycin clearance and glomerular filtration rate (GFR).
Results: In total, 104 elderly patients were included. The patients had a median age of 75 (72 - 92) years, total body weight of 72.3 (62.8 – 84.7) kg, and GFR of 92 (74.7 - 99) mL/min/1,73m². The found vancomycin clearance, volume of distribution and half-life values were: 3.4 (2.8 – 4.7) L/h, 55.4 (43.2 – 69.7) L and 9.8 (7.6 – 13.8) hours, respectively. The therapeutic target was initially achieved in 35 (34%) patients, and 49 (47%) patients had supratherapeutic AUC (> 600 mg.h/L), considering MIC 1 mg/L. Dosing adjustments were made based on individual parameters to optimize target attainment, and the median corrected vancomycin daily dose was 1165 (854 – 1404) mg. Vancomycin clearance and GFR showed low correlation value (R² = 0.20).
Conclusion: Neglecting to tailor doses to individual needs of elderly patients can lead to an increased risk of vancomycin-induced nephrotoxicity due to unnecessarily high total drug exposure. The vancomycin monitoring based on PK/PD approach permits real-time dose adjustments based on individual pharmacokinetics.
Presenting Author
Amanda Veiga BScUniversity of São Paulo
Authors
Vanessa Juodinis PharmB
Sírio-Libanês Hospital
Ronaldo Morales Jr. PhD
Sírio-Libanês Hospital
Alex Silva BSc
Hospital Sírio Libanês