Definition of Sub-phenotypes of Pneumonia Based on the Respiratory Microbiome Composition to Predict Microbial and Clinical Treatment Failures
Background: Pneumonia remains a leading cause of antibiotic consumption globally, contributing significantly to the burden of antimicrobial resistance (AMR). The respiratory microbiome plays a crucial role in the emergence of AMR and therapeutic failure in both community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). The PHENOMENON study aims to investigate the relationship between the respiratory microbiome composition and clinical outcomes to improve the prediction of treatment failure and AMR emergence.
Methods: This multicenter prospective cohort study will include 300 adult patients across three cohorts: CAP in general wards, severe CAP in intensive care units (ICU), and ventilator-associated HAP (vHAP/VAP). Patients will undergo oropharyngeal and rectal swabbing at admission (Day 0), Day 3, Day 7-10, and Day 90, along with blood sampling and endotracheal aspirates in intubated patients. The primary objective is to assess the association between baseline respiratory microbiome composition and time to antibiotic response within 7-10 days. The composite primary endpoint includes clinical failure, microbiological failure, or AMR emergence. Secondary endpoints explore the association between microbiome composition and pneumonia recurrence, severity, hospital length of stay, and mortality at Day 28 and Day 90. Expected Outcomes: This study will provide insights into the predictive value of respiratory microbiome composition on antibiotic response and AMR emergence. Understanding these relationships may guide personalized antibiotic strategies and optimize pneumonia management, ultimately reducing treatment failure rates and improving patient outcomes.
• 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