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 Leone,
Adrien Bouglé,
iDIAPASON Trial Investigators
Affiliations
Arnaud Foucrier
Department of Anesthesiology and Critical Care, Beaujon Hospital, DMU Parabol, AP-HP Nord, Université de Paris
Thomas Dessalle
Department of Anesthesia, Critical Care and Perioperative Care, Pitié-Salpetrière Hospital
Sophie Tuffet
Department of Clinical Pharmacology-Clinical Research Platform, AP-HP, Sorbonne University
Laura Federici
Service de Réanimation Polyvalente, Centre Hospitalier d′Ajaccio
Claire Dahyot‑Fizelier
Department of Anaesthesia and Intensive Care, University Hospital of Poitiers
François Barbier
Service de Médecine Intensive-Réanimation, Centre Hospitalier Régional d’Orléans
Julien Pottecher
Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Department of Anaesthesiology, Critical Care and Perioperative Medicine, Fédération de Médecine Translationnelle de Strasbourg, ER 3072, Strasbourg University Hospital
Antoine Monsel
Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, GRC 29, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University
Tarik Hissem
General Intensive Care Unit, Sud-Essonne Hospital
Jean‑Yves Lefrant
UR-UM103 IMAGINE, Univ. Montpellier, Division of Anesthesia Critical Care, Pain and Emergency Medicine, Nîmes University Hospital, Montpellier, France, Nîmes University Hospital
Alexandre Demoule
Service de Médecine Intensive et Réanimation (Département R3S), APHP, Site Pitié-Salpêtrière, Sorbonne Université
Jean‑Michel Constantin
Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care, GRC 29, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University
Alexandra Rousseau
Department of Clinical Pharmacology-Clinical Research Platform, AP-HP, Sorbonne University
Tabassome Simon
Department of Clinical Pharmacology-Clinical Research Platform, AP-HP, Sorbonne University
Marc Leone
Service d’anesthésie et de Réanimation, Hôpital Nord, Assistance Publique Hôpitaux de Marseille, Aix Marseille Université
Adrien Bouglé
Department of Anesthesiology and Critical Care Medicine, Cardiology Institute, GRC 29, AP-HP, Pitié-Salpêtrière Hospital, Sorbonne University
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.
