Fatal Granulibacter bethesdensis Infection in Chronic Granulomatous Disease Diagnosed by Plasma Microbial Cell-Free DNA Sequencing

Granulibacter bethesdensis is a rare pathogen primarily reported in patients with chronic granulomatous disease (CGD). We present a fatal case of G. bethesdensis infection in a man in his late 20s with CGD who presented with fever, nausea, and abdominal pain. He was found to have generalized lymphadenopathy, but an extensive conventional infectious workup failed to identify an etiology. Despite broad-spectrum antimicrobial therapy, his condition progressed to profound sepsis, and he ultimately died. Cell-free DNA (cfDNA) testing of a blood specimen subsequently identified G. bethesdensis after his death. This case highlights the diagnostic challenges associated with this uncommon pathogen and the potential role of early cfDNA testing in patients with CGD and unexplained severe infection. Clinicians should consider G. bethesdensis in patients with CGD presenting with sepsis and progressive lymphadenopathy to facilitate earlier diagnosis and targeted antimicrobial therapy.