Timing of Bronchoscopy and Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Host Pneumonia

Abstract Background Immunocompromised patients are at high risk of pneumonia, with associated poor outcomes. Rapid microbiologic diagnosis is crucial, yet diagnostic yields vary widely. We evaluated the variability in diagnostic yield of usual care testing and plasma microbial cell-free DNA (mcfDNA) sequencing in the prospective observational Pneumonia in the Immunocompromised—Use of the Karius Test for the Detection of Undiagnosed Pathogens (PICKUP) study, specifically focusing on timing of testing relative to the onset of pneumonia. Methods In this exploratory analysis, patient characteristics, variability in diagnostic yield, and the timing of bronchoscopy and mcfDNA sequencing from date of first abnormal imaging associated with suspected pneumonia were evaluated across enrolling sites. Results A total of 222 patients from 10 enrolling sites were analyzed. Usual care diagnostic yield varied across sites (range, 7.7%–57.7%). Patient characteristics did not differ between sites, and median time from abnormal imaging to bronchoscopy was not different across sites (3 days [IQR, 3]). Diagnostic yield of bronchoscopy was significantly higher when performed ≤3 days (early) from abnormal imaging (38.5% [52/135]) versus >3 days (delayed) (21.8% [19/87]) (difference, 16.7% [95% CI, 2.5%–28.3%]; P = .009). Adding mcfDNA sequencing to usual care testing increased overall diagnostic yield by 7.9% for patients undergoing early bronchoscopy, and by 16.3% for delayed bronchoscopy. Conclusions Early bronchoscopy enhances diagnostic yield in immunocompromised patients with suspected pneumonia. Irrespective of timing, plasma mcfDNA sequencing increases overall diagnostic yield in this clinical scenario. These findings underscore the importance of prompt diagnostic strategies in this patient population.