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

Inclusion Criteria28

  • 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
  • Criteria for severe ventilator-associated pneumonia defined as:
  • Vasopressor therapy for onset of septic shock around the time of ventilator-associated pneumonia suspicion
  • Onset or severe worsening of hypoxemia (PaO2/FiO2\<150 with 60% FiO2 and 10 mm H2O peak expiratory pressure, or patient on veno-venous extracorporeal membrane oxygenation)
  • Immunosuppression defined as :
  • leukocytes \<1G/L or neutrophils \<0,5 G/L
  • within the last 3 months
  • hematopoietic stem-cell transplant or organ transplant with chronic immunosuppressant therapy
  • HIV infection with CD4\<50/mm3
  • chronic corticosteroid use (\>0.5 mg/kg day for at least one month within the last three months).
  • Patient already on Antibiotic Therapy of predicted duration ≥4 weeks (endocarditis, spondylodiscitis, abscess...)
  • Previous ventilator-associated pneumonia suspicion with sampling and/or Antibiotic Therapy for suspected ventilator-associated pneumonia
  • Previous inclusion in the trial
  • Patient included in an interventional study on ventilator-associated pneumonia management with the same primary endpoint.
  • Pregnancy, recent delivery, or breastfeeding
  • Correctional facility inmate, adult under guardianship
  • Patient under legal protection
  • Life expectancy less than 48 hours and/or decision to withhold and/or withdraw life-sustaining therapies
  • Organ donor reanimation

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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