Ceftriaxone to prevent early ventilator-associated pneumonia in patients with acute brain injury: a multicentre, randomised, double-blind, placebo-controlled, assessor-masked superiority trial
Claire Dahyot-Fizelier
(1, 2, 3)
,
Sigismond Lasocki
(4)
,
Thomas Kerforne
(3)
,
Pierre-Francois Perrigault
(5)
,
Thomas Geeraerts
(6)
,
Karim Asehnoune
(7)
,
Raphaël Cinotti
(7)
,
Yoann Launey
(8)
,
Vincent Cottenceau
(9)
,
Marc Laffon
(10)
,
Thomas Gaillard
(4)
,
Matthieu Boisson
(2, 3, 1)
,
Camille Aleyrat
(3)
,
Denis Frasca
(3)
,
Olivier Mimoz
(2, 1, 3)
,
Claire Dahyot-Fizelier
(1, 2, 3)
,
Sigismond Lasocki
(4)
,
Thomas Kerforne
(3)
,
Thomas Geeraerts
(6)
,
Karim Asehnoune
(7)
,
Raphaël Cinotti
(7)
,
Yoann Launey
(8)
,
Vincent Cottenceau
(9)
,
Marc Laffon
(10)
,
Thomas Gaillard
(4)
,
Matthieu Boisson
(2, 3, 1)
,
Camille Aleyrat
(3)
,
Clément Guyonnaud
(3)
,
Rémy Bellier
,
Thierry Benard
(3)
,
Elsa Carise
(3)
,
Franck Petitpas
(11)
,
Hodanou Nanadoumgar
(3, 12, 1)
,
Nadia Imzi
(3)
,
Sabrina Seguin
(3)
,
Karine Garnier
,
Véronique Ferrand-Rigallaud
,
Séverine Clerjaud
,
Soizic Gergaud
(4, 13)
,
Flora Djanikian
(5, 14)
,
Kevin Chalard
(5, 15)
,
Ségolène Mrozek
(6)
,
Sylvain Panh
,
Antoine Roquilly
(7, 16)
,
Bertrand Rozec
(17)
,
Philippe Seguin
(8)
,
Yannick Malledant
(8, 18)
,
Djilali Elaroussi
,
Martine Ferrandiere
,
Matthieu Biais
1
Université de Poitiers - UFR Santé [Faculté de Médecine et de Pharmacie]
2 PHAR2 [Poitiers] - Pharmacologie des anti-infectieux et antibiorésistance [U 1070]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 CHU Angers - Centre Hospitalier Universitaire d'Angers
5 Hôpital Gui de Chauliac [CHU Montpellier]
6 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
9 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
10 CHU Trousseau [Tours]
11 Service de Réanimation Chirurgicale
12 Modélisations pharmacocinétiques-pharmacodynamiques pour un meilleur usage des anti-infectieux
13 UA - Université d'Angers
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 IGF - Institut de Génomique Fonctionnelle
16 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
17 Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
18 NuMeCan - Nutrition, Métabolismes et Cancer
2 PHAR2 [Poitiers] - Pharmacologie des anti-infectieux et antibiorésistance [U 1070]
3 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
4 CHU Angers - Centre Hospitalier Universitaire d'Angers
5 Hôpital Gui de Chauliac [CHU Montpellier]
6 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
8 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
9 CHU Bordeaux - Centre Hospitalier Universitaire de Bordeaux
10 CHU Trousseau [Tours]
11 Service de Réanimation Chirurgicale
12 Modélisations pharmacocinétiques-pharmacodynamiques pour un meilleur usage des anti-infectieux
13 UA - Université d'Angers
14 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
15 IGF - Institut de Génomique Fonctionnelle
16 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
17 Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
18 NuMeCan - Nutrition, Métabolismes et Cancer
Thomas Kerforne
- Fonction : Auteur
- PersonId : 1364278
- ORCID : 0000-0002-0611-4100
- IdRef : 172292212
Karim Asehnoune
- Fonction : Auteur
- PersonId : 1221700
- ORCID : 0000-0003-1899-3517
Matthieu Boisson
- Fonction : Auteur
- PersonId : 793363
- ORCID : 0000-0003-3667-5782
- IdRef : 163923787
Olivier Mimoz
- Fonction : Auteur
- PersonId : 1162006
- ORCID : 0000-0003-1737-7915
- IdRef : 058753613
Rémy Bellier
- Fonction : Auteur
Karine Garnier
- Fonction : Auteur
Véronique Ferrand-Rigallaud
- Fonction : Auteur
Séverine Clerjaud
- Fonction : Auteur
Sylvain Panh
- Fonction : Auteur
Djilali Elaroussi
- Fonction : Auteur
Martine Ferrandiere
- Fonction : Auteur
Matthieu Biais
- Fonction : Auteur
Résumé
Background: Patients with acute brain injury are at high risk of ventilator-associated pneumonia (VAP). The benefit of short-term antibiotic prophylaxis remains debated. We aimed to establish the effect of an early, single dose of the antibiotic ceftriaxone on the incidence of early VAP in patients with severe brain injury who required mechanical ventilation.Methods: PROPHY-VAP was a multicentre, randomised, double-blind, placebo-controlled, assessor-masked, superiority trial conducted in nine intensive care units in eight French university hospitals. We randomly assigned comatose (Glasgow Coma Scale score [GCS] ≤12) adult patients (age ≥18 years) who required mechanical ventilation for at least 48 h after acute brain injury to receive intravenous ceftriaxone 2 g or placebo once within the 12 h following tracheal intubation. Participants did not receive selective oropharyngeal and digestive tract decontamination. The primary outcome was the proportion of patients developing early VAP from the 2nd to the 7th day of mechanical ventilation, confirmed by masked assessors. The analysis was reported in the modified intention-to-treat population, which comprised all randomly assigned patients except those who withdrew or did not give consent to continue and those who did not receive the allocated treatment because they met a criterion for non-eligibility. The trial is registered with ClinicalTrials.gov, NCT02265406.Findings: From Oct 14, 2015, to May 27, 2020, 345 patients were randomly assigned (1:1) to receive ceftriaxone (n=171) or placebo (n=174); 330 received the allocated intervention and 319 were included in the analysis (162 in the ceftriaxone group and 157 in the placebo group). 166 (52%) participants in the analysis were men and 153 (48%) were women. 15 patients did not receive the allocated intervention after randomisation and 11 withdrew their consent. Adjudication confirmed 93 cases of VAP, including 74 early infections. The incidence of early VAP was lower in the ceftriaxone group than in the placebo group (23 [14%] vs 51 [32%]; hazard ratio 0·60 [95% CI 0·38-0·95], p=0·030), with no microbiological impact and no adverse effects attributable to ceftriaxone.Interpretation: In patients with acute brain injury, a single ceftriaxone dose decreased the risk of early VAP. On the basis of our findings, we recommend that an early, single dose of ceftriaxone be included in all bundles for the prevention of VAP in patients with brain injury who require mechanical ventilation.