Evaluation of once daily tobramycin dosing in critically ill patients through Bayesian simulation.

Abstract

To evaluate if once-daily dose (ODD) regimens of tobramycin attain pharmacodynamic goals using individualized pharmacokinetic monitoring of critically ill patients with creatinine clearance (Clcr) over 60 mL/min. Fifty-one adult critically ill patients treated with intravenous tobramycin with ODD were included in the study. The effect of dosing using the proposed method was compared with a weight-based (7 mg/kg) dosing method. Pharmacokinetics parameters, peak concentration (Cpeak), minimum concentration (Cmin) and the time below the minimum inhibitory concentration (MIC) were estimated using Bayesian analysis. Pharmacodynamic parameters used to evaluate both dosing regimens were Cpeak/MIC ratio and, secondly, time below MIC (T< MIC). The median dose of tobramycin administrated in our hospital was too low for achieving pharmacodynamic goals. In contrast, the weight-based (7 mg/kg) method produced an adequate Cpeak/MIC ratio but an increase of the dose would not reduce the secondary pharmacodynamic index T<MIC. The results from the current study explain why weight-based daily dosing of tobramycin in critically ill patients with Clcr>60 mL/min achieved the Cpeak/MIC target values of 10. However in critically ill patients with Clcr>80 mL/min, T<MIC is greater than the aminoglycoside post-antibiotic effect, so these patients do not attain the secondary pharmacodynamic index. These data show the need for rapid pharmacokinetic optimization with individualized aminoglycoside dosing. Additional studies are necessary to better define the best tobramycin regimen for critically ill patients.