RecruitingNot ApplicableNCT06743529

Immediate Versus Substantiated Antibiotic Therapy in Suspected Non-Severe Ventilator-Associated Pneumonia

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


Sponsor

Nantes University Hospital

Enrollment

686 participants

Start Date

Nov 11, 2025

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study compares two approaches to treating a type of lung infection called ventilator-associated pneumonia (VAP) in ICU patients on breathing machines: giving antibiotics immediately when pneumonia is suspected versus waiting for lab results to confirm the diagnosis before starting antibiotics. The goal is to reduce unnecessary antibiotic use. **You may be eligible if...** - You are 18 or older - You have been on a mechanical ventilator (breathing machine) for more than 48 hours - Doctors suspect you have ventilator-associated pneumonia (new lung changes on X-ray plus fever or abnormal blood counts or thick secretions) - A respiratory sample was collected less than 2 hours ago **You may NOT be eligible if...** - You are in septic shock or have severely low oxygen levels (severe VAP) - Your immune system is severely weakened (very low white blood cell count, organ transplant on immunosuppressants, HIV with very low CD4 count, or high-dose steroids) - You are already on long-term antibiotics - This is a second episode of suspected VAP - You are pregnant or breastfeeding - Your life expectancy is less than 48 hours Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

PROCEDUREcontrol group

immediate empiric Antibiotic Therapy (started within 1 hour after randomization) with antibiotic(s) chosen by the bedside physician based on time of ventilator-associated pneumoniaoccurrence, risk of antimicrobial resistance, local ecology, and local protocol. If the respiratory samples are negative, Antibiotic Therapy will be stopped. If ventilator-associated pneumonia is confirmed by positive samples, Antibiotic Therapy active against the recovered bacterial specie(s) will be given for a total of 7 days.

PROCEDUREConservative strategy

No Antibiotic Therapy until receipt of the respiratory sample culture and/or polymerase chain reaction results. If these results are negative, no Antibiotic Therapy is given. If they are positive (confirmed ventilator-associated pneumonia), Antibiotic Therapy is started as appropriate for the bacterial specie(s) detected by culture and/or polymerase chain reaction, without considering gram-stain results and without waiting for antimicrobial susceptibility testing results, and continued for a total of 7 days of Antibiotic Therapy active against the identified bacterial specie(s).


Locations(41)

CHU Angers

Angers, France, France

CH Angoulème

Angoulème, France, France

CH Argenteuil

Argenteuil, France, France

CHU Nantes

Nantes, France, France

CH d'Arles

Arles, France

CH Avignon

Avignon, France

Hôpital Nord Franche Comté

Belfort, France

CHU de Bordeaux

Bordeaux, France

CHU de Bordeaux

Bordeaux, France

CH Simone Veil

Cannes, France

CH Public du Cotentin

Cherbourg, France

CH Cholet

Cholet, France

CHU Clermont-Ferrand

Clermont-Ferrand, France

CH Dax

Dax, France

CHU Dijon

Dijon, France

APHP - Hôpital Raymond Poincaré

Garches, France

CHD Vendée

La Roche-sur-Yon, France

CH Versailles

Le Chesnay, France

CH Le Mans

Le Mans, France

CH Emile Roux

Le Puy-en-Velay, France

CHRU Lille

Lille, France

GHB Sud- Hôpital de Lorient

Lorient, France

CHU de Lyon - Hôpital Edouard Herriot

Lyon, France

CH de Melun

Melun, France

CH de Mont de Marsan

Mont-de-Marsan, France

CHU Nice -Hôpital Pasteur

Nice, France

CHU Nice - Hôpital de l'Archet

Nice, France

CHR d'Orléans

Orléans, France

APHP - Hôpital Cochin

Paris, France

APHP - Hôpital Tenon

Paris, France

CH de Pau

Pau, France

CHU Rennes

Rennes, France

CH de Saint-Nazaire

Saint-Nazaire, France

CH de Saint-Malo

St-Malo, France

CHRU de Strasbourg - Nouvel Hôpital Civil

Strasbourg, France

CHRU de Strasbourg -Hôpital de Hautepierre

Strasbourg, France

Hôpital Foch

Suresnes, France

CHRU De Tours

Tours, France

CH de Valenciennes

Valenciennes, France

CH Bretagne Atlantique

Vannes, France

CHU La Guadeloupe

Pointe-à-Pitre, Guadeloupe

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NCT06743529


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