title: Comparison of 30-min and 3-h infusion regimens for imipenem/cilastatin and for meropenem evaluated by Monte Carlo simulation.
abstract: 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.
authors.affiliation: Bassett Healthcare, Cooperstown, NY 13326, USA.
authors.forename: Lois S
authors.initials: LS
authors.lastname: Lee
authors.forename: Martina
authors.initials: M
authors.lastname: Kinzig-Schippers
authors.forename: Anne N
authors.initials: AN
authors.lastname: Nafziger
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Fritz
authors.initials: F
authors.lastname: Sörgel
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bertino
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015377:Cilastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077728:Cilastatin, Imipenem Drug Combination; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D009010:Monte Carlo Method; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D000077731:Meropenem