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Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against
M E Klepser1, K B Patel, D P Nicolau
1College of Pharmacy, University of Iowa, Iowa City 52242-1112, USA.
Study Objective:
To describe the pharmacokinetic profiles of vancomycin administered by continuous infusion and intermittent dosing and compare the duration of activity of the regimens.
Design:
Randomized, open-label, crossover study.
Setting:
Clinical research center at an academic medical center.
Subjects:
Twelve healthy, nonpregnant volunteers age 27.6 +/- 2.3 years.
Intervention:
Subjects received the following intravenous vancomycin regimens: 1 g every 12 hours; 2 g continuous infusion over 24 hours; and 1 g continuous infusion over 24 hours. Dosages were administered with and without gentamicin 2 mg/kg.
Measurements And Main Results:
Serum samples were collected, drug concentrations determined, and bactericidal activity measured against two isolates each of methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Subjects had poor tolerability for continuous infusions. Trough concentration for the intermittent regimen was 5.5 +/- 1.9 mg/ml, and steady-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 provided cidal activity for a significantly greater percentage of the dosing interval (p<0.001).
Conclusion:
Continuous infusion does not greatly improve the activity of vancomycin and should not be routinely administered. However, it may prove useful against isolates with reduced susceptibility to the agent.