• Int. J. Antimicrob. Agents · Nov 2012

    Randomized Controlled Trial

    Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia.

    • Sutep Jaruratanasirikul, Wibul Wongpoowarak, Narongdet Kositpantawong, Nanchanit Aeinlang, and Monchana Jullangkoon.
    • Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. jasutep@medicine.psu.ac.th
    • Int. J. Antimicrob. Agents. 2012 Nov 1; 40 (5): 434-9.

    AbstractSeveral pathophysiological changes in critically ill patients are important in determining the therapeutic success of β-lactam antibiotics. The aim of this study was to assess the population pharmacokinetics and probabilities of target attainment (PTAs) of doripenem in patients with ventilator-associated pneumonia, comparing administration by 1-h and 4-h infusion. Patients were randomised into two groups: Group I received a 1-h infusion of 0.5 g every 8 h (q8h) for seven doses; and Group II received a 4-h infusion of 0.5 g q8h for seven doses. A Monte Carlo simulation was performed to determine the PTAs. PTAs of achieving 40% T(>MIC) [exposure time during which the free drug concentration remains above the minimum inhibitory concentration (MIC)] and 75% T(>MIC) are required for effective bactericidal activity of this agent in immunocompetent and immunocompromised hosts, respectively. Values of volume of distribution and total clearance of doripenem in these patients were 17.26±1.83 L and 24.89±1.63 L/h, respectively. For pathogens with a MIC of 1 μg/mL, the PTAs of achieving 40% T(>MIC) following administration of doripenem by a 1-h and 4-h infusion of 0.5 g q8h were 92.95% and 98.32%, respectively. For pathogens with a MIC of 2 μg/mL in immunocompromised hosts, the PTAs of achieving 80% T(>MIC) following administration of doripenem by 1-h and 4-h infusion of 2 g q8h were 56.57% and 91.21%, respectively. In conclusion, these findings indicated that higher than recommended doses in this patient population, particularly neutropenic patients, would be necessary to optimise the pharmacokinetics of doripenem.Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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