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.