Efficacy and Safety of Intravenous Infusion of Doripenem Versus Imipenem in Ventilator-Associated Pneumonia: A Multicenter, Randomized Study

Crit Care Med. 2008 Apr;36(4):1089-96. doi: 10.1097/CCM.0b013e3181691b99.


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 with imipenem for the treatment of ventilator-associated pneumonia.

Design: Prospective, multicenter, parallel randomized, active-controlled, open-label study.

Setting: Intensive care units.

Patients: Adults (N = 531) who met clinical and radiologic criteria for ventilator-associated pneumonia.

Interventions: Patients were stratified by duration of mechanical ventilation (< 5 vs. > or = 5 days), severity of illness (Acute Physiology and Chronic Health Evaluation II score < or = 15 vs. > 15), and geographic region and then randomly assigned to doripenem 500 mg every 8 hrs via a 4-hr intravenous infusion or imipenem 500 mg every 6 hrs or 1000 mg every 8 hrs via 30- or 60-min intravenous infusions, respectively, for 7-14 days.

Measurements and main results: The primary efficacy end points were the clinical cure rates in the clinical modified intent-to-treat (cMITT) and clinically evaluable populations. Doripenem was noninferior to imipenem (lower boundary of 95% confidence interval around the difference between treatments > or = -20%). Clinical cure rates were 68.3% (doripenem) and 64.2% (imipenem) in the clinically evaluable and 59.0% (doripenem) and 57.8% (imipenem) in the cMITT populations. In patients with Pseudomonas aeruginosa, clinical cure was 80.0% (doripenem) and 42.9% (imipenem) (p not significant); microbiological cure was 65.0% (doripenem) and 37.5% (imipenem). Only 18% (5 of 28) of P. aeruginosa isolates had minimum inhibitory concentration > or = 8 microg/mL at baseline or following therapy in the doripenem arm compared with 64% (16 of 25) in the imipenem treatment group (p = .001). Clinical cure rate was higher with doripenem than imipenem at higher Acute Physiology and Chronic Health Evaluation II scores and older ages. Doripenem was generally well tolerated.

Conclusions: In this large, phase III study of patients with ventilator-associated pneumonia, a 4-hr intravenous infusion of doripenem was clinically efficacious and therapeutically noninferior to imipenem.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Carbapenems / administration & dosage
  • Carbapenems / adverse effects
  • Carbapenems / therapeutic use*
  • Doripenem
  • Female
  • Hospital Mortality
  • Humans
  • Imipenem / administration & dosage
  • Imipenem / adverse effects
  • Imipenem / therapeutic use*
  • Infusions, Intravenous
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pneumonia, Ventilator-Associated / classification
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Pneumonia, Ventilator-Associated / microbiology
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Carbapenems
  • Imipenem
  • Doripenem