A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia.
Crit Care. 2012 Nov 13;16(6):R218
Authors: Kollef MH, Chastre J, Clavel M, Restrepo MI, Michiels B, Kaniga K, Cirillo I, Kimko H, Redman R
Abstract
ABSTRACT: INTRODUCTION: 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. METHODS: A prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem 1 gram as a 4-hour infusion every 8 hours with a fixed 10-day course of imipenem-cilastatin 1 gram as a 1-hour infusion every 8 hours (April 2008 through June 2011). RESULTS: 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 Pseudomonas aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). CONCLUSIONS: 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 7 days to optimize clinical outcome. Trial registration: clinicaltrials.gov NCT00589693.
PMID: 23148736 [PubMed - as supplied by publisher]