Critically ill, immunocompromised individuals are vulnerable to both common and uncommon etiologies of respiratory infection. Identifying the etiology of infection has therapeutic, prognostic, and public health implications. In some circumstances, immunocompromised patients may be empirically treated with excessively broad antibiotics but ultimately be diagnosed with a common cause of pneumonia. In other circumstances, immunocompromised patients may have a non-specific clinical presentation for severe respiratory failure and be diagnosed with a rare etiology of infection. Because this patient population is at risk for a broad array of infections, it is important to understand the advantages and limitations of sampling and diagnostic techniques. Furthermore, the last decades of research have produced novel methods to enhance diagnostic accuracy. Many of these tests are molecular diagnostics that have high sensitivity, but their clinical impact is unknown, particularly in immunocompromised individuals. In this article we discuss various approaches to sampling and microbiologic diagnosis in immunocompromised individuals with severe respiratory failure.

Received: 03 December 2025

Accepted: 06 February 2026

Article published online:
28 February 2026

© 2026. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA