Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia.
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
medline:
5
12
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
ppublish
Résumé
Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).
Sections du résumé
BACKGROUND
BACKGROUND
Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear.
METHODS
METHODS
In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed.
RESULTS
RESULTS
A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group.
CONCLUSIONS
CONCLUSIONS
Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).
Identifiants
pubmed: 37888914
doi: 10.1056/NEJMoa2310307
doi:
Substances chimiques
Amikacin
84319SGC3C
Anti-Bacterial Agents
0
Banques de données
ClinicalTrials.gov
['NCT03149640']
EudraCT
['2016-001054-17']
Types de publication
Equivalence Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
2052-2062Subventions
Organisme : Ministère des Solidarités et de la Santé
ID : Projet hospitalier de recherche clinique PHRC-15-2
Investigateurs
Stephan Ehrmann
(S)
Emmanuelle Mercier
(E)
Denis Garot
(D)
Charlotte Salmon Gandonniere
(C)
François Barbier
(F)
Mai-Anh Nay
(MA)
Dalila Benzekri
(D)
Ferhat Meziani
(F)
Julien Demiselle
(J)
Hamid Merdji
(H)
Julie Helms
(J)
Alexandra Monnier
(A)
Julian Kaurin
(J)
Jean-Pierre Quenot
(JP)
Pascal Andreu
(P)
Jean-Etienne Herbrecht
(JE)
Raphaël Clere-Jehl
(R)
Ralf Janssen-Langenstein
(R)
Maleka Schrnck-Dhif
(M)
Vincent Castelain
(V)
Damien Roux
(D)
Noémie Zucman
(N)
Jean-Claude Lacherade
(JC)
Marie-Ange Azais
(MA)
Mickaël Landais
(M)
Marjorie Saint-Martin
(M)
Philippe Seguin
(P)
Yoann Launey
(Y)
Elodie Masseret
(E)
David Schnell
(D)
Laurence Robin
(L)
Yolène Roy
(Y)
Anne Veinstein
(A)
Benoît Veber
(B)
Thomas Clavier
(T)
Philippe Gouin
(P)
Sigismond Lasocki
(S)
Maeva Campfort
(M)
Qin Lu
(Q)
Antoine Monsel
(A)
Charlotte Arbelot
(C)
Corinne Vezinet
(C)
Gaëtan Beduneau
(G)
Martine Ferrandiere
(M)
Anne-Charlotte Tellier
(AC)
Mathilde Barbaz
(M)
Gaëtan Plantefeve
(G)
Claire Dahyot-Fizelier
(C)
Claude Guerin
(C)
Nader Chebib
(N)
Informations de copyright
Copyright © 2023 Massachusetts Medical Society.