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

• DOI: 10.1007/s00134-022-06690-5
• Publication Date: 2022-05-13T10:03:59Z
• Authors: Adrien Bouglé; Sophie Tuffet; Laura Federici; Marc Leone; Antoine Monsel; Thomas Dessalle; Julien Amour; Claire Dahyot-Fiz...; 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 Const...; Alexandra Rousseau; Tabassome Simon; Arnaud Foucrier; ; Adrien Bouglé; Julien Amour; Thomas Dessalle; Florence Bellenfa...; Bernard Cholley; Julien Massot; Jean-Michel Const...; Alexandre Demoule; Julien Mayaux; Vincent Dubée; Hervé Dupont; Jacques Duranteau; Laura Federici; Arnaud Foucrier; Thomas Geeraerts; Céline Guichon; Pierre Kalfon; Éric Kipnis; Sigismond Lasocki; Jean-Yves Lefrant; Matthieu Legrand; Marc Leone; Thomas Lescot; Bruno Lévy; Joël Cousson; Philippe Montravers; Sébastien Tanaka; Emmanuel Novy; Alexandre Ouattara; Jean-François Payen; Walter Picard; Pascale Poète; Julien Pottecher; Christophe Quesnel; Muriel Fartoukh; Anoine Tesniere; Mélanie Fromentin; Jean-Jacques Rouby; Qin Lu; Olivier Langeron; Pierre Squara; Eric Levesque; Nicolas Mongardon; Tabassome Simon; Laurence Berard; Marine Cachanado; Nora Soussi
• Keywords: Ventilator-associated Pneumonia; Clinical endpoint; Bacterial pneumonia

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).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.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.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.