Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

Abstract

PURPOSE:

Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).

METHODS:

We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.

RESULTS:

The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.

CONCLUSIONS:

Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

• Authors: Adrien Bouglé, Sophie Tuffet, Laura Federici, Marc Leone, Antoine Monsel, Thomas Dessalle, Julien Amour, Claire Dahyot-Fizelier, François Barbier, Charles-Edouard Luyt, Olivier Langeron, Bernard Cholley, Julien Pottecher, Tarik Hissem, Jean-Yves Lefrant, Benoit Veber, Matthieu Legrand, Alexandre Demoule, Pierre Kalfon, Jean-Michel Constantin, Alexandra Rousseau, Tabassome Simon, Arnaud Foucrier, iDIAPASON Trial Investigators
• Journal: Intensive care medicine (Intensive Care Med) Vol. 48 Issue 7 Pg. 841-849 (07 2022) ISSN: 1432-1238 [Electronic] United States
• PMID: 35552788 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Anti-Bacterial Agents

Topics

• Adult
• Anti-Bacterial Agents (therapeutic use)
• Humans
• Intensive Care Units
• Pneumonia, Ventilator-Associated (epidemiology)
• Pseudomonas aeruginosa
• Respiration, Artificial