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Impact of Goal-Oriented and Model-Based Clinical Pharmacokinetic Dosing of Aminoglycosides on Clinical Outcome: A Cost-Effectiveness Analysis

van Lent-Evers, Nicolette A. E. M.*; Mathôt, Ron A. A.*; Geus, William P.; van Hout, Ben A.; Vinks, Alexander A. T. M. M.*


The benefits of a pharmacy-based, active therapeutic drug monitoring (TDM) service (ATM) on outcomes were examined in a prospective study at four hospitals. ATM involved pharmacokinetic dosage optimization at the start of treatment, subsequent Bayesian adaptive control, and frequent patient evaluation. Cost-effectiveness was calculated based on real costs. The ATM group comprised 105 patients and 127 patients with nonguided TDM who were followed up as controls. Forty-eight of the ATM and 62 of the nonguided TDM patients had an infection on admission. Peak concentrations in ATM patients were significantly higher (10.6 ± 2.9 mg/L; nonguided TDM, 7.6 ± 2.2 mg/L; p < 0.01). Trough levels in the ATM group were significantly lower (p < 0.01). There was a trend toward lower mortality in the ATM group (nine of 105 versus 18 of 127; p = 0.26) that was significant for patients with an infection on admission (one of the 48 ATM patients died versus nine of the 62 nonguided TDM patients; p = 0.023). ATM reduced the length of hospital stay for all patients in the study (20.0 ± 1.4 days; nonguided TDM, 26.3 ± 2.9 days; p = 0.045) and for patients admitted with an infection (12.6 ± 0.8 days; nonguided TDM, 18.0 ± 1.4; p < 0.001). The incidence of nephrotoxicity was reduced from 13.4% (nonguided TDM) to 2.9% (p < 0.01). With ATM, total costs were lower for all patients (Dutch guilders [DFL], 13,125 ± 9,267; nonguided TDM, DFL 16,862 ± 17,721; p < 0.05) and for patients admitted with an infection (DFL 8,883 ± 3,778; nonguided TDM, DFL 11,743 ± 7,437; p < 0.01). Goal-oriented, model-based dosing of aminoglycosides resulted in higher antibiotic efficacy, shorter hospitalization, and reduced incidence of nephrotoxicity. By combining efficacy with savings, ATM offered a significant alternative to usual care.

*TDM and Clinical Toxicology Laboratory, The Hague Central Hospital Pharmacy, The Hague, †Department of Intensive Care, Leyenburg Hospital, The Hague, Department of Gastroenterology, Leiden University Medical Center, Leiden, and the ‡Institute for Medical Technology Assessment (iMTA), Erasmus University, Rotterdam, The Netherlands

Dr. van Lent-Evers is currently at the Department of Clinical Pharmacy, Lorentz Hospital, Zeist, The Netherlands

Received August 26, 1998; accepted September 25, 1998.

Address correspondence and reprint requests to Alexander A. T. M. M. Vinks, Central Hospital Pharmacy, P.O. Box 43100, 2504 AC The Hague, The Netherlands.

Copyright © 1999 Wolters Kluwer Health, Inc. All rights reserved.