Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis

• Published in: Pharmacotherapy Vol. 18; no. 5; p. 1069
• Main Authors: Klepser, M E, Patel, K B, Nicolau, D P, Quintiliani, R, Nightingale, C H
• Format: Journal Article
• Language: English
• Published: United States 01.09.1998
• Subjects: Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Biological Availability; Cross-Over Studies; Enterococcus faecalis; Female; Gram-Positive Bacterial Infections - drug therapy; Half-Life; Humans; Infusions, Intravenous; Male; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcal Infections - drug therapy; Staphylococcus aureus; Vancomycin - administration & dosage; Vancomycin - pharmacokinetics
• ISSN: 0277-0008
• DOI: 10.1002/j.1875-9114.1998.tb03936.x

To describe the pharmacokinetic profiles of vancomycin administered by continuous infusion and intermittent dosing and compare the duration of activity of the regimens. Randomized, open-label, crossover study. Clinical research center at an academic medical center. Twelve healthy, nonpregnant volunteers age 27.6 +/- 2.3 years. 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. 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). 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.