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
Authors: Foucrier Arnaud , Dessalle Thomas , Tuffet Sophie , Federici Laura , Dahyot‑Fizelier Claire , Barbier François , Pottecher Julien , Monsel Antoine , Hissem Tarik , Lefrant Jean‑Yves , Demoule Alexandre , Constantin Jean‑Michel , Rousseau Alexandra , Simon Tabassome , Leone Marc , Bouglé Adrien ,   iDIAPASON Trial Investigators, Bouglé Adrien , Amour Julien , Dessalle Thomas , Zegdi Florence Bellenfant , Cholley Bernard , Massot Julien , Constantin Jean-Michel , Demoule Alexandre , Mayaux Julien , Dubée Vincent , Dupont Hervé , Duranteau Jacques , Federici Laura , Foucrier Arnaud , Geeraerts Thomas , Guichon Céline , Kalfon Pierre , Kipnis Éric , Lasocki Sigismond , Lefrant Jean-Yves , Legrand Matthieu , Leone Marc , Lescot Thomas , Lévy Bruno , Cousson Joël , Montravers Philippe , Tanaka Sébastien , Novy Emmanuel , Ouattara Alexandre , Payen Jean-François , Picard Walter , Poète Pascale , Pottecher Julien , Quesnel Christophe , Fartoukh Muriel , Tesniere Anoine , Fromentin Mélanie , Rouby Jean-Jacques , Lu Qin , Langeron Olivier , Squara Pierre , Levesque Eric , Mongardon Nicola ,   Methodology and biostatistics team, Simon Tabassome , Berard Laurence , Cachanado Marine , Soussi Nora 
Published: May 2023

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.