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

Abstract

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.

The role of antibiotic stewardship in limiting antibacterial resistance among hematology patients

“…23 Aminoglycoside dosing is optimized via the administration of large (once daily) doses up to 7 mg/kg for gentamicin and tobramycin and up to 20 mg/kg for amikacin, aiming at a serum peak/MIC ratio of 8-12 (individual MIC or local data), which also minimizes nephrotoxicity. 28 Active therapeutic drug monitoring 29 should be performed to avoid toxic drug levels arising via accumulation. Optimization of vancomycin dosing is achieved by using a loading dose (up to 35 mg/kg) and ensuring optimal trough levels of approximately 15 mg/L, either by twice-daily administration or continuous infusion, in order to achieve an (AUC) 0-24 : MIC ratio of more than 400, which correlates with positive outcomes in patients with MRSA bacteremia.…”

Treatment of extensively drug-resistant Gram-negative infections in critically ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of Clinical Microbiology and Infection, October 2012

“…PK/PD modelling suggests that a daily 10 mg/kg dose of gentamicin or tobramycin provides an 80% probability of response, even for an MIC of 4.0 mg/mL, with a negligible likelihood of toxicity [16]. As stated before, the dosage regimen for the individual patient needs to ensure an adequate drug exposure in this patient in relation to the MIC and should be re-evaluated according to TDM [17].…”

Population Pharmacokinetic–Pharmacodynamic (PK/PD) Modeling of Anti-infective Agents and Its Applications to Individualized Therapy

“…Ideally, a process of therapeutic drug management is adopted that combines the measurement of drug levels with the application of pharmacokinetic and pharmacodynamic principles. A few prospective studies using population models and Bayesian feedback have shown the superiority of model-based PK/PD guidance, both in terms of cost effectiveness and better clinical outcomes including better survival (van Lent-Evers et al 1999;Leon-Djian et al 2011).…”