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Randomized Controlled Trial
. 2023 May 30;27(1):211.
doi: 10.1186/s13054-023-04457-y.

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  1 , Thomas Dessalle  2 , Sophie Tuffet  3 , Laura Federici  4 , Claire Dahyot-Fizelier  5 , François Barbier  6 , Julien Pottecher  7 , Antoine Monsel  8 , Tarik Hissem  9 , Jean-Yves Lefrant  10 , Alexandre Demoule  11 , Jean-Michel Constantin  8 , Alexandra Rousseau  3 , Tabassome Simon  3 , Marc Leone  12 , Adrien Bouglé  13 ; iDIAPASON Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

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 et al. Crit Care. .

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.

Keywords: Antibiotic therapy; Combination therapy; Pseudomonas aeruginosa; Ventilator-associated pneumonia.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Survival curves of the survival probability for death in ICU (Kaplan–Meier estimates). Survival probability is for the 90 days since the start of appropriate antibiotic therapy
Fig. 2
Fig. 2
Evolution of the SOFA score according to the type of adapted antibiotic therapy
See this image and copyright information in PMC

Comment in

References

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