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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.CC

Abstract

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.

Authors+Show Affiliations

Service de Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Université Pierre et Marie Curie Paris 6, Paris, France. jean.chastre@psl.aphp.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18379232

Citation

Chastre, Jean, et al. "Efficacy and Safety of Intravenous Infusion of Doripenem Versus Imipenem in Ventilator-associated Pneumonia: a Multicenter, Randomized Study." Critical Care Medicine, vol. 36, no. 4, 2008, pp. 1089-96.
Chastre J, Wunderink R, Prokocimer P, et al. Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Crit Care Med. 2008;36(4):1089-96.
Chastre, J., Wunderink, R., Prokocimer, P., Lee, M., Kaniga, K., & Friedland, I. (2008). Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. Critical Care Medicine, 36(4), 1089-96. https://doi.org/10.1097/CCM.0b013e3181691b99
Chastre J, et al. Efficacy and Safety of Intravenous Infusion of Doripenem Versus Imipenem in Ventilator-associated Pneumonia: a Multicenter, Randomized Study. Crit Care Med. 2008;36(4):1089-96. PubMed PMID: 18379232.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator-associated pneumonia: a multicenter, randomized study. AU - Chastre,Jean, AU - Wunderink,Richard, AU - Prokocimer,Philippe, AU - Lee,Michael, AU - Kaniga,Koné, AU - Friedland,Ian, PY - 2008/4/2/pubmed PY - 2008/4/29/medline PY - 2008/4/2/entrez SP - 1089 EP - 96 JF - Critical care medicine JO - Crit Care Med VL - 36 IS - 4 N2 - 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. SN - 1530-0293 UR - https://www.unboundmedicine.com/medline/citation/18379232/Efficacy_and_safety_of_intravenous_infusion_of_doripenem_versus_imipenem_in_ventilator_associated_pneumonia:_a_multicenter_randomized_study_ L2 - https://dx.doi.org/10.1097/CCM.0b013e3181691b99 DB - PRIME DP - Unbound Medicine ER -