Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial
Arnaud Foucrier, Thomas Dessalle, Sophie Tuffet, Laura Federici, Claire Dahyot‐Fizelier, François Barbier, Julien Pottecher, Antoine Monsel, Tarik Hissem, Jean‐Yves Lefrant, Alexandre Demoule, Jean‐Michel Constantin, Alexandra Rousseau, Tabassome Simon, Marc Léone, Adrien Bouglé, iDIAPASON Trial Investigators, Adrien Bouglé, Julien Amour, Thomas Dessalle, Florence Bellenfant Zegdi, Bernard Cholley, Julien Massot, Jean‐Michel Constantin, 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 Lü, Olivier Langeron, Pierre Squara, Éric Levesque, Nicola Mongardon, Methodology and biostatistics team, Tabassome Simon, Laurence Bérard, Marine Cachanado, Nora Soussi
Abstract
BACKGROUND: The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator‑associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP. METHODS: Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test. RESULTS: A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission. CONCLUSIONS: Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group. TRIAL REGISTRATION: NCT02634411 , Registered 15 December 2015.