Comparison of 30-min and 3-h infusion regimens for imipenem/cilastatin and for meropenem evaluated by Monte Carlo simulation.

Author(s): Lee LS, Kinzig-Schippers M, Nafziger AN, Ma L, Sorgel F, Jones RN, Drusano GL, Bertino JS Jr

Affiliation(s): Bassett Healthcare, Cooperstown, NY 13326, USA.

Publication date & source: 2010-11, Diagn Microbiol Infect Dis., 68(3):251-8. Epub 2010 Sep 18.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

Imipenem/cilastatin and meropenem are carbapenem antibiotics that are infused intravenously (IV) over 30 to 45 min. We evaluated probability of target attainment and cumulative probability of target attainment of 30-min and 3-h infusions for imipenem/cilastatin and meropenem. Eighteen healthy adults in a randomized, 4-phase, crossover study received 1000 mg of imipenem/cilastatin or meropenem as a single-dose IV over 30 min or 3 h. A population pharmacokinetics analysis using a 2-compartment IV infusion model was performed. Monte Carlo simulations using various dosage regimens at steady-state and 30-min and 3-h infusion rates were performed to evaluate the probabilities of attaining 20% (bacteriostatic), 30%, and 40% (maximum kill) time above the MIC. Three-hour infusions of imipenem/cilastatin and meropenem improved the cumulative probability of target attainment for a variety of populations of microorganisms compared to 30-min infusions. Prolonged infusions have the potential to optimize efficacy of imipenem/cilastatin and meropenem. Copyright (c) 2010 Elsevier Inc. All rights reserved.