Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: A multicenter, randomized study*

• DOI: 10.1097/ccm.0b013e3181691b99
• Publication Date: 2009-03-04T00:51:57Z
• Authors: Jean Chastre; Richard Wunderink; Philippe Prokocimer; Michael Lee; Koné Kaniga; Ian Friedland
• Keywords: Doripenem; Ventilator-associated Pneumonia; Carbapenem

Objective: Doripenem is an investigational carbapenem with broad-spectrum activity against Gram-negative and Gram-positive pathogens, including multidrug-resistant strains, commonly responsible for ventilator-associated pneumonia (VAP). This large, phase III study compared doripenem imipenem the treatment of pneumonia. Design: Prospective, multicenter, parallel randomized, active-controlled, open-label study. Setting: Intensive care units. Patients: Adults (N = 531) who met clinical radiologic criteria Interventions: Patients were stratified by duration mechanical ventilation (<5 vs. ≥5 days), severity illness (Acute Physiology Chronic Health Evaluation II score ≤15 >15), geographic region then randomly assigned to 500 mg every 8 hrs via a 4-hr intravenous infusion or 6 1000 30- 60-min infusions, respectively, 7–14 days. Measurements Main Results: The primary efficacy end points cure rates in modified intent-to-treat (cMITT) clinically evaluable populations. was noninferior (lower boundary 95% confidence interval around difference between treatments ≥−20%). Clinical 68.3% (doripenem) 64.2% (imipenem) 59.0% 57.8% cMITT In patients Pseudomonas aeruginosa, 80.0% 42.9% (p not significant); microbiological 65.0% 37.5% (imipenem). Only 18% (5 28) P. aeruginosa isolates had minimum inhibitory concentration ≥8 μg/mL at baseline following therapy arm 64% (16 25) group .001). rate higher than Acute scores older ages. generally well tolerated. Conclusions: this pneumonia, efficacious therapeutically imipenem.