Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational...

Area of Science:

• Medical Diagnostics
• Infectious Diseases
• Genomics

Background:

• Pneumonia is a significant cause of illness and death, often with an unidentified pathogen.
• Diagnosing pneumonia in immunocompromised patients is challenging, necessitating improved methods.

Purpose of the Study:

• To evaluate the additive diagnostic value of plasma microbial cell-free DNA sequencing.
• To compare this novel sequencing method with standard diagnostic approaches in immunocompromised adults with pneumonia.

Main Methods:

• A prospective, multicenter, observational study compared plasma microbial cell-free DNA sequencing to usual care in immunocompromised adults undergoing bronchoscopy.
• The primary outcome was the additive diagnostic value, defined as pneumonia etiologies exclusively identified by plasma sequencing.

Main Results:

• Plasma microbial cell-free DNA sequencing exclusively identified pneumonia etiology in 12.1% of patients (P < .001).
• In patients with negative usual care testing, plasma sequencing achieved a clinical additive diagnostic value of 17.4%.

Conclusions:

• Non-invasive plasma microbial cell-free DNA sequencing substantially enhances diagnostic yield for pneumonia in immunocompromised patients.
• This technique provides valuable complementary information to existing extensive testing protocols.