Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia.
Int J Antimicrob Agents. 2012 Sep 6;
Authors: Jaruratanasirikul S, Wongpoowarak W, Kositpantawong N, Aeinlang N, Jullangkoon M
Several pathophysiological changes in critically ill patients are important in determining the therapeutic success of ?-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 0.5g every 8h (q8h) for seven doses; and Group II received a 4-h infusion of 0.5g 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±1.83L and 24.89±1.63L/h, respectively. For pathogens with a MIC of 1?g/mL, the PTAs of achieving 40% T(>MIC) following administration of doripenem by a 1-h and 4-h infusion of 0.5g q8h were 92.95% and 98.32%, respectively. For pathogens with a MIC of 2?g/mL in immunocompromised hosts, the PTAs of achieving 80% T(>MIC) following administration of doripenem by 1-h and 4-h infusion of 2g 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.
PMID: 22959555 [PubMed - as supplied by publisher]