Background: The use of intra-vesicular Bacille Calmette-Guerin (BCG) for bladder cancer can result in disseminated/endovascular BCG infection. The diagnosis of BCGosis in this setting is complicated by the risks of biopsy of an endovascular focus and the long duration of acid-fast bacilli (AFB) cultures.
Methods: A 68 year-old male with a history of hypertension, aortic aneurysm (status post repair) and bladder cancer treated with intravesicular BCG complicated by BCGosis presented several years later with two weeks of fevers, chills, night sweats and back pain. Computed tomography (CT) scan demonstrated aortitis with periaortic abscess. There was concern for BCG aortitis given the antecedent BCG exposure and prior BCGosis. Blood cultures were negative; AFB blood cultures were contaminated. A sample of plasma was sent to Karius (Redwood City, CA) for next generation sequencing (NGS). Cell-free DNA was extracted and NGS performed. Human sequences were removed and remaining sequences were aligned to a curated pathogen database of > 1000 organisms. Organisms present above a statistical threshold were reported. The patient underwent surgical replacement of the infected endograft; endovascular samples were sent for AFB culture.
Results: Plasma-based NGS of cell free DNA detected Mycobacterium tuberculosis (Mtb) complex at 48 hrs (within 28 hrs of sample receipt). Within the Mtb complex, the majority of sequences aligned to Mycobacterium bovis with five reads aligning uniquely to M. bovis. No reads aligned to the region of deletion 1 (RD1) deleted in BCG. Surgical AFB cultures were positive for Mtb complex by PCR probe at nine days; Mtb complex was recovered in culture at nineteen days.
Conclusion: Plasma metagenomic sequencing can be used to rapidly diagnose BCG-associated endovascular infection.
L. Blair, Karius: Employee , Salary .
S. Bercovici, Karius, Inc.: Employee , Salary .
A. Ahmed, Karius, Inc.: Employee , Salary .