mNGS -Guided Antimicrobial Treatment in Early Severe Community-Acquired Pneumonia Among Immunocompromised Patients

Severe Community-acquired pneumonia (SCAP) is a leading global infectious cause of intensive care unit (ICU) admission (approximately 20%-30%), and the primary reason of mortality and morbidity in immunocompromised patients. There is a global increase of patients with distinct immunocompromised conditions due to the advance of cancer treatment, increasing biologics, and immunosuppressants for autoimmune diseases and growing organ transplant recipients, and it has been estimated that patients with immunocompromised conditions account for approximately 35% of all intensive care unit (ICU) admissions. Immunocompromised patients with SCAP have more factors to complicate with sepsis, respiratory failure, acute respiratory distress syndrome, and the mortality rate can be up to 50%. With the aim to apply early accurate antimicrobial therapy to improve clinical prognosis of SCAP patients with immunocompromised conditions, timely identification of pathogen is particularly important. Conventional microbiological diagnostic methods such as standard microbiologic cultures, microscopy, polymerase chain reaction (PCR), respiratory virus multiplex PCR, as well as pathogen-specific antigens and antibody assays, are currently commonly used to detect pathogens, although they have various limitations. However, conventional antimicrobial therapy depends on the results of conventional diagnostic methods, which may delay timely accurate antimicrobial therapy at the initial stage, and the mortality of immunocompromised patients with SCAP may be increased. Metagenomic next-generation sequencing (mNGS), which can determine pathogens more quickly (usually within 24h) and accurately comparing with conventional diagnostic methods by analyzing cell-free nucleic acid fragments of pathogens using appropriate lower respiratory tract (LRT) specimen, is increasingly used in severe respiratory infectious disease, especially among immunocompromised patients. This study aims to determine whether mNGS (using LRT specimen) guided antimicrobial treatment improves clinical prognosis of SCAP patients with immunocompromised conditions when compared with conventional antimicrobial treatment.