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The Impact of Early Adequate Treatment on Extubation and Discharge Alive of Patients With Pseudomonas aeruginosa-Related Ventilator-Associated Pneumonia*

Sommer, Harriet, PhD1; Timsit, Jean-François, MD, PhD2,3; von Cube, Maja, MSc1; Schumacher, Martin, PhD1; Darmon, Michael, MD, PhD4; Schwebel, Carole, MD, PhD5; Ruckly, Stéphane, MSc6; Wolkewitz, Martin, PhD1 on behalf of COMBACTE-MAGNET Consortium

doi: 10.1097/CCM.0000000000003305
Clinical Investigations

Objectives: We aim to examine the effect of early adequate treatment in comparison with inadequate or delayed treatment on being extubated or discharged alive over time, in patients with Pseudomonas aeruginosa-related ventilator-associated pneumonia.

Design: Retrospective analyses of a prospective observational multicenter cohort study.

Setting: ICU.

Patients: Patients of the French prospective database (OUTCOMEREA) were included if they acquired a ventilator-associated pneumonia due to P. aeruginosa between 1997 and 2014 and were mechanically ventilated for more than 48 hours.

Interventions: Early adequate treatment in comparison with inadequate or delayed adequate treatment.

Measurements and Main Results: Multistate models were applied to estimate the time-dependent probability of being extubated or discharged alive, and separate Cox regression analyses were used to assess the treatment effect on all important events that influence the outcome of interest. A propensity score-adjusted innovative regression technique was used for a combined and comprehensive patient-relevant summary effect measure. No evidence was found for a difference between adequate and inadequate or delayed treatment on being extubated or discharged alive. However, for all patients, the probability of being extubated or discharged alive remains low and does not exceed 50% even 40 days after a P. aeruginosa-related ventilator-associated pneumonia.

Conclusions: Early adequate treatment does not seem to be associated with an improved prognosis. Its potential benefit requires further investigation in larger observational studies.

1Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center – University of Freiburg, Freiburg, Germany.

2UMR 1137 IAME Inserm/Université Paris Diderot, F75018, Paris, France.

3APHP Medical and Infectious Diseases ICU, Bichat Hospital, Paris, France.

4APHP, Hôpital Saint Louis Paris, Paris, France.

5Centre Hospitalier Universitaire de Grenoble, Grenoble, France.

6Outcomerea Network, Paris, France.

*See also p. 1703.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Drs. Sommer and Timsit and Ms. von Cube were supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement n [115737-2 – COMBACTE-MAGNET], resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies. Dr. Wolkewitz received funding from the German Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: sommer@imbi.uni-freiburg.de

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