Effect of individualized pharmacokinetic dosing on patient outcome.

Abstract

To study the effect of individualized pharmacokinetic dosing of aminoglycosides on patient outcome. Prospective, randomized study. Tertiary care hospital. Ninety-five patients with documented Gram-negative infections received 97 courses of aminoglycoside therapy. Patients were randomized between pharmacokinetic dose adjustment and monitoring or traditional physician-directed techniques. Patients were stratified by severity of underlying illness before randomization. Sixty-two courses of treatment were satisfactorily completed. Patients in the severely ill group (eight kinetic, eight traditional) had significantly (p less than .05) better survival (7 kinetic, 3 traditional) when managed with pharmacokinetic consultation. The kinetic arm received greater doses (156 +/- 59 mg/dose; 2.4 +/- 0.6 mg/kg) than the traditional arm (81 +/- 27 mg/dose; 1.5 +/- 0.6 mg/kg) (p less than .001). In addition, the dose per day (mg/kg) was greater in the kinetic arm (4.1 +/- 1.5) than the traditional arm (3.2 +/- 1.3) (p less than .001). The improved survival was achieved by attaining therapeutic peak serum concentrations earlier in the course of the infection and by administering more total aminoglycoside without increasing toxicity. We conclude that pharmacokinetic management of aminoglycoside dosing may improve the outcome of severely ill patients.