COMPARISON OF BACTERICIDAL ACTIVITIES OF INTERMITTENT AND CONTINUOUS-INFUSION DOSING OF VANCOMYCIN AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCUS-AUREUS AND ENTEROCOCCUS-FAECALIS

Study Objective. To describe the pharmacokinetic profiles of vancomyci n administered by continuous infusion and intermittent dosing and comp are the duration of activity of the regimens. Design. Randomized, open -label, crossover study Setting. Clinical research center at an academ ic medical center. Subjects. Twelve healthy nonpregnant volunteers age 27.6 +/- 2.3 years. Intervention. Subjects received the following int ravenous vancomycin regimens: 1 g every 12 hours; 2 g continuous infus ion over 24 hours; and 1 g continuous infusion over 24 hours. Dosages were administered with and without gentamicin 2 mg/kg. Measurements an d Main Results. Serum samples were collected, drug concentrations dete rmined, and bactericidal activity measured against two isolates each o f methicillin-resistant Staphylococcus aureus and Enterococcus faecali s. Subjects had poor tolerability for continuous infusions. Trough con centration for the intermittent regimen was 5.5 +/- 1.9 mg/ml, and ste ady-state concentrations were 8.8 +/- 1.6 and 16.9 +/- 1.9 mg/ml for 1 and 2 g continuous infusions, respectively. In general, all regimens provided bactericidal activity throughout the study interval. Against one isolate of E. faecalis, 2 g continuous infusion plus gentamicin pr ovided cidal activity for a significantly greater percentage of the do sing interval (p<0.001). Conclusion. Continuous infusion does not grea tly improve the activity of vancomycin and should not be routinely adm inistered. However, it may prove useful against isolates with reduced susceptibility to the agent.