Immediate Versus Substantiated Antibiotic Therapy in Suspected Non-Severe Ventilator-Associated Pneumonia: A Randomized Controlled Trial

Status: Recruiting
Location: See all (41) locations...
Intervention Type: Procedure
Study Type: Interventional
Study Phase: Not Applicable
SUMMARY

Ventilator-associated pneumonia is the leading nosocomial infection in the intensive care units, and is associated with prolonged mechanical ventilation and overuse of antibiotics. Initiating antibiotic therapy immediately after bacteriological sampling (immediate strategy) may expose uninfected patients to unnecessary treatment, while waiting for bacteriological confirmation (conservative strategy) may delay ventilator-associated pneumonia in infected patients. The decision to start antibiotic therapy for ventilator-associated pneumonia takes three points into account: diagnostic probability, the risks to the patient if Antibiotic Therapy is delayed, and the risk of selection of resistant bacteria. Diagnostic probability is limited, given the subjective and non-specific nature of the diagnostic criteria, and only 30-50% of suspected cases are confirmed bacteriologically (whereas samples are only taken when the pre-test probability is sufficient). The risks associated with delayed antibiotic therapy are unknown, as few observational studies have directly assessed the impact of the timing of Antibiotic Therapy initiation on outcome (frequent confusion between delayed and inappropriate Antibiotic Therapy). Iregui et al. found that delaying Antibiotic Therapy by more than 24 hours was associated with higher mortality. However, more recent before-and-after studies have shown that the conservative strategy was associated with lower mortality, more frequently appropriate initial Antibiotic Therapy and shorter duration of Antibiotic Therapy. Similarly, in a recent before-and-after study by our team, initiating antibiotic therapy only upon microbiological confirmation of ventilator-associated pneumonia without septic shock or severe acute respiratory distress syndrome was not associated with an increase in ventilation time, length of stay or excess mortality at D28; but was associated with antibiotic therapy that was more often appropriate (DELAVAP, MARTIN et al, Annals of Intensive Care, 2024). Finally, the recent multicenter TARPP pilot study in surgical intensive care suggests that antibiotic therapy initiated on the basis of microbiological data in patients with suspected ventilator-associated pneumonia not requiring vasopressor support is not associated with a poorer outcome than immediate antibiotic therapy without documentation (the only randomized study on this subject). Antibiotic Therapy for suspected ventilator-associated pneumonia that is not subsequently confirmed is an unnecessary use of antibiotics and carries a risk of selection of resistant bacteria, with adverse effects on public health. It has been reported that a conservative Antibiotic Therapy prescription strategy for intensive care units -acquired infections reduces Antibiotic Therapy use and the incidence of acquired β-lactamase-producing Enterobacteriaceae infections. Overall, in patients with suspected ventilator-associated pneumonia but no signs of clinical severity, given the uncertainty about attributable mortality and concerns about bacterial resistance, the evaluation of the conservative Antibiotic Therapy strategy is reasonable. Some French intensive care units already delay Antibiotic Therapy until confirmation of ventilator-associated pneumonia, except in patients with severe hypoxemia or the need for vasopressor support.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Invasive mechanical ventilation for longer than 48 hours

• Respiratory sample collection taken less than two hours ago (at physician discretion, according to local protocol) for a first episode of suspected ventilator-associated pneumonia (meeting the following prespecified criteria) :

‣ new or changing chest X-ray infiltrates

⁃ plus at least two of the following:

• body temperature ≥38.5°C or ≤35.5°C,

∙ blood leukocyte count \>12 000/µL or \<4000/µL,

∙ purulent tracheobronchial aspirate.

• Age ≥18 years

• Informed consent from the patient or next of kin to participation in the trial, or emergency procedure if no next of kin is available

• Patients affiliated to a social security system

Locations
Other Locations
France
CHU Angers
RECRUITING
Angers
CH Angoulème
RECRUITING
Angoulème
CH Argenteuil
RECRUITING
Argenteuil
CH d'Arles
RECRUITING
Arles
CH Avignon
RECRUITING
Avignon
Hôpital Nord Franche Comté
RECRUITING
Belfort
CHU de Bordeaux
RECRUITING
Bordeaux
CHU de Bordeaux
RECRUITING
Bordeaux
CH Simone Veil
RECRUITING
Cannes
CH Public du Cotentin
RECRUITING
Cherbourg
CH Cholet
RECRUITING
Cholet
CHU Clermont-Ferrand
RECRUITING
Clermont-ferrand
CH Dax
RECRUITING
Dax
CHU Dijon
RECRUITING
Dijon
APHP - Hôpital Raymond Poincaré
RECRUITING
Garches
CHD Vendée
RECRUITING
La Roche-sur-yon
CH Versailles
RECRUITING
Le Chesnay
CH Le Mans
RECRUITING
Le Mans
CH Emile Roux
RECRUITING
Le Puy-en-velay
CHRU Lille
RECRUITING
Lille
GHB Sud- Hôpital de Lorient
RECRUITING
Lorient
CHU de Lyon - Hôpital Edouard Herriot
RECRUITING
Lyon
CH de Melun
RECRUITING
Melun
CH de Mont de Marsan
RECRUITING
Mont-de-marsan
CHU Nantes
RECRUITING
Nantes
CHU Nice - Hôpital de l'Archet
RECRUITING
Nice
CHU Nice -Hôpital Pasteur
RECRUITING
Nice
CHR d'Orléans
RECRUITING
Orléans
APHP - Hôpital Cochin
RECRUITING
Paris
APHP - Hôpital Tenon
RECRUITING
Paris
CH de Pau
RECRUITING
Pau
CHU Rennes
RECRUITING
Rennes
CH de Saint-Nazaire
RECRUITING
Saint-nazaire
CH de Saint-Malo
RECRUITING
St-malo
CHRU de Strasbourg - Nouvel Hôpital Civil
RECRUITING
Strasbourg
CHRU de Strasbourg -Hôpital de Hautepierre
RECRUITING
Strasbourg
Hôpital Foch
RECRUITING
Suresnes
CHRU De Tours
RECRUITING
Tours
CH de Valenciennes
RECRUITING
Valenciennes
CH Bretagne Atlantique
RECRUITING
Vannes
Guadeloupe
CHU La Guadeloupe
RECRUITING
Pointe-à-pitre
Contact Information
Primary
Maëlle MARTIN
maelle.martin@chu-nantes.fr
0240 087 365
Time Frame
Start Date: 2025-11-11
Estimated Completion Date: 2029-02-11
Participants
Target number of participants: 686
Treatments
Active_comparator: Immediate strategy
Usual Care
Experimental: Conservative strategy
Conservative strategy
Sponsors
Leads: Nantes University Hospital

This content was sourced from clinicaltrials.gov