Individualized dosing of vancomycin in geriatric patients.

Abstract

Aims: Pharmacotherapy in geriatric patients is challenging due to frequent multimorbidity, polypharmacy, increased risk of adverse drug effects, and altered pharmacokinetics and pharmacodynamics associated with aging. Therapeutic drug monitoring (TDM) is a dosing individualisation strategy that helps to minimise toxicity whilst maximising the efficacy of the agent. Routine TDM of vancomycin is recommended in clinical practice in order to optimise drug exposure. Guidelines by Rybak et al. from 2009 on vancomycin TDM promote monitoring of trough concentrations only, with higher target ranges for dosage adjustment. The aim of the study was to evaluate the practice of vancomycin TDM in geriatric (aged 65 ys) and non-geriatric patients, compare two methods of dosing adjustment (trough-based vs. AUC-based approach), and finally determine covariates enabling to choose an appropriate initial vancomycin maintenance dosing regimen in geriatric patients.   Methods: A retrospective analysis of all vancomycin plasma concentrations determined during a five year period in patients treated with IV vancomycin in the University Hospital Olomouc was performed. Haemodialysis patients were excluded. Each trough value was compared with the guidelines by Rybak et al. and subsequently, pharmacokinetic modelling was performed to assess individual AUC24 values.

Results: A total of 1,458 vancomycin concentrations were included, which represented 799 individual monitoring events in 380 patients. Vancomycin was most commonly prescribed for sepsis (41.6% of all patients). Pathogens with MIC > 1 mg/L were responsible for 16.7% of all infections. Initial dosing led to optimum vancomycin exposure in 37.8% of patients. Vancomycin dosage based on the guidelines by Rybak et al. from 2009 would agree with the AUC-based dosing adjustments in 65% of all monitoring events. Approximately 19.1% of trough concentrations were below the minimum target suggested by the guidelines despite the fact that their corresponding AUC24/MIC ratios were high enough ( 400), and in further 6.1% of monitoring events, the trough-only approach would fail to accurately identify supratherapeutic concentrations. Initial dosing of 1 g twice daily was prescribed to 62.9% of patients, although it would be considered as optimal only in 32.1% of all patients. For 48 % of patients in the non-geriatric cohort, higher dosing (3 to 4 g daily) would be necessary to achieve optimum vancomycin exposure, whereas for 56% of geriatric patients, lower dosage regimens (up to 1.5 g daily) would be considered optimal. The estimated glomerular filtration rate was the most significant covariate in the pharmacokinetic model enabling the construction of a dosing nomogram.

Conclusion: AUC-based vancomycin monitoring is superior to trough-based approach as the latter can lead to unnecessarily aggressive dosing in over a quarter of patients. A simple nomogram using the estimated glomerular filtration rate may increase the percentage of patients receiving an optimal initial vancomycin dose.