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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

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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230680/
https://www.ncbi.nlm.nih.gov/pubmed/37254209
http://dx.doi.org/10.1186/s13054-023-04457-y
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author 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
author_facet 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
author_sort Foucrier, Arnaud
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04457-y.
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spelling pubmed-102306802023-06-01 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 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 Crit Care Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-023-04457-y. BioMed Central 2023-05-30 /pmc/articles/PMC10230680/ /pubmed/37254209 http://dx.doi.org/10.1186/s13054-023-04457-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
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
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10230680/
https://www.ncbi.nlm.nih.gov/pubmed/37254209
http://dx.doi.org/10.1186/s13054-023-04457-y
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