Defining pneumonia subtypes by respiratory microbiome to predict treatment failure

Definition of Sub-phenotypes of Pneumonia Based on the Respiratory Microbiome Composition to Predict Microbial and Clinical Treatment Failures

This project will see if patterns in the respiratory microbiome can predict antibiotic or clinical treatment failures in adults hospitalized with community-acquired or hospital-acquired pneumonia.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 6 sites (Clichy and 5 other locations)
• Trial ID: NCT06916481 on ClinicalTrials.gov

What this trial studies

PHENOMENON is a multicenter prospective cohort enrolling 300 adults across three cohorts: community-acquired pneumonia in general wards, severe CAP in intensive care units, and ventilator-associated or VAP in ventilated patients. Participants will provide oropharyngeal and rectal swabs at admission (Day 0), Day 3, Day 7–10 and Day 90, plus blood samples and endotracheal aspirates when intubated. The study will compare baseline and longitudinal respiratory microbiome compositions with clinical outcomes and the emergence of antimicrobial resistance to identify sub-phenotypes linked to microbial and clinical treatment failure. Results aim to generate predictive signatures that could inform future targeted interventions.

Who should consider this trial

Good fit: Adults (age ≥18) hospitalized with community-acquired pneumonia in medical wards, severe CAP in the ICU, or ventilator-associated HAP/VAP who can provide the required respiratory and rectal samples and meet timing criteria are eligible.

Not a fit: Children, outpatients, patients not hospitalized at participating centers, or those unable to provide respiratory or stool samples are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this work could help clinicians identify patients at higher risk of antibiotic failure or resistance earlier and guide more targeted treatment choices.

How similar studies have performed: Previous smaller studies have linked respiratory microbiome patterns to outcomes and antimicrobial resistance, but large multicenter prospective efforts to predict treatment failure remain limited.

Eligibility criteria

Inclusion Criteria:

* Cohort 1: CAP at emergency department and requiring hospitalization in general wards :

  * Age ≥18 years
  * Hospitalization in a medical department (not ICU)
  * Presence of at least one acute clinical sign compatible with pneumonia (e.g. dyspnea, cough, purulent sputum or purulent tracheal aspirations or crackles), and temperature above 38°C in the 48 hours prior to inclusion
  * AND new pulmonary infiltrate on chest X-ray or CT scan (on Day 0 or within three days of inclusion)
  * Efficient treatment initiated for less than 24 hours
  * Sputum collection possible
* Cohort 2: Severe CAP with ICU hospitalization :

  * Age ≥18 years
  * Hospitalization in intensive care unit for at least 24 hours.
  * Presence of at least one acute clinical sign compatible with pneumonia (e.g. dyspnoea, cough, purulent sputum or crackles), temperature greater than 38°C in the 48 hours prior to hospital admission
  * AND new pulmonary infiltrate on chest X-ray or CT scan (on Day 0 or within three days of inclusion)
  * Efficient treatment initiated for less than 24 hours
  * Sputum collection or tracheal aspiration or any distal bacterial sample (BAL, plugged telescopic catheter) collection possible
* Cohort 3: vHAP or VAP :

  * Age ≥18 years
  * vHAP: mechanical ventilation, in a patient previously hospitalized for more than 48 hours at the onset of new or worsening radiological infiltrates and 2 of the following: fever or hypothermia, leukocytosis \> 12 G/L or leukopenia \< 4G/L, purulent tracheal aspirates,
  * VAP: mechanical ventilation for more than 48 hours, new or worsening radiological infiltrates and 2 of the following: fever (\>38°C) or hypothermia (\<36.5°C) in the 24 hours prior to inclusion, leucocytosis\> 12 G/L or leukopenia \< 4G/L, purulent tracheal aspirates
  * AND plugged telescopic catheter (PTC) ≥103colony-forming units (CFU)/ml or bronchoalveolar lavage (BAL) culture ≥104 CFU/ml or purulent tracheal aspirates ≥ 106 UFC/mL
  * AND treated with active antibiotic therapy for pneumonia for less than 24 hours

Exclusion Criteria:

* Cohort 1: CAP with hospitalization in general wards :

  * AIDS
  * Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
  * Bone marrow transplant patients
  * Cancer patients undergoing chemotherapy within 3 months of inclusion
  * Opposition of the patient (absence of informed written consent)
  * Scheduled transfer to another hospital
  * Patient under guardianship or comparable legal status
  * NB: Patients included in the cohort 1 and referred to ICU within the first 24 hours will be included in the cohort 2.
* Cohort 2: Severe CAP with ICU hospitalization :

  * AIDS
  * Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
  * Bone marrow transplant patients
  * Cancer patients undergoing chemotherapy within 3 months of inclusion
  * Stays shorter than 24h in the ICU will be exlcuded
  * Absence of informed written consent of the patient if they are fit, or absence of informed written consent of the relative/caregiver (for patients unable to understand the information and in the absence of a relative/caregiver, emergency inclusion is authorized)
  * Decision to forego life-sustaining therapy
  * Patient under guardianship or comparable legal status
* Cohort 3: vHAP or VAP :

  * AIDS
  * Patient on high-dose corticosteroids \>2 mg/kg prednisone equivalent
  * Bone marrow transplant patients
  * Cancer patients undergoing chemotherapy within 3 months of inclusion
  * Absence of informed written consent of the patient if he is fit, or absence of informed written consent of the relative (for patients unable to understand the information and in the absence of a relative, emergency inclusion is authorized)
  * Decision to forego life-sustaining therapy
  * Patient under guardianship or comparable legal status

Where this trial is running

Clichy and 5 other locations

• Hospital Beaujon — Clichy, France (Active_not_recruiting)
• CHU Nantes - Saint Herblain — Nantes, France (Not_yet_recruiting)
• CHU Nantes - Saint Herblain — Nantes, France (Not_yet_recruiting)
• CHU Nantes — Nantes, France (Active_not_recruiting)
• Hospital Bichat — Paris, France (Recruiting)
• Hospital Bichat — Paris, France (Active_not_recruiting)

Study contacts

• Study coordinator: Jean-françois TIMSIT, MD, PHD

Conditions Community Acquired or Acquiring Hospital Acquired Pneumonia; Pneumonia, respiratory microbiome, antibiotic treatment