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A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia

Marin H Kollef1*, Jean Chastre2, Marc Clavel3, Marcos I Restrepo4, Bart Michiels5, Koné Kaniga6, Iolanda Cirillo6, Holly Kimko6 and Rebecca Redman6

Author Affiliations

1 Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, 660 South Euclid Avenue, Campus Box 8052, St. Louis, MO 63110, USA

2 Service de Réanimation Médicale, Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651 Paris Cedex 13, France

3 Centre Hospitalier De Limoges, Hospital Dupuytren 02 Ave, Martin Luther King 87000, Limoges, France

4 Division of Pulmonary/Critical Care Medicine, University of Texas Health Science Center at San Antonio and Division Pulmonary/Critical Care Medicine, South Texas Veterans Health Care System, 7400 Merton Minter Blvd. (11c6), San Antonio, TX, 78229 USA

5 Janssen Research and Development, Turnhoutsewig 30, 2340, Beerse, Belguim

6 Janssen Pharmaceutical Research and Development, 1000 Route 202, Raritan, NJ, 08869 USA

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Critical Care 2012, 16:R218  doi:10.1186/cc11862

Published: 13 November 2012



The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria.


This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011).


The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0).


Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome.

Trial Registration NCT00589693