Curated cases from the TB expert network: Unplugged! Series: Use of plasma microbial cell-free DNA metagenomic sequencing to diagnose Mycobacterium tuberculosis

A 52-year-old U.S.-born man with diabetes and a kidney transplant 3 months prior presented with fever of unknown origin and left-sided weakness. On admission, he was found to have right internal carotid artery thrombus and cerebral infarct. He developed respiratory failure and underwent treatment for Pseudomonas bacteremia. Fevers continued through hospital day 30 and computed tomography (CT) scans demonstrated an esophageal mass, hepatic lesions, and pulmonary nodules, which were new compared to pre-transplant imaging 2 years prior. While awaiting results from acid-fast bacilli (AFB) cultures from sputum and tissue, plasma microbial cell-free DNA (mcfDNA) metagenomic sequencing was ordered on day 29 and was positive for Mycobacterium Tuberculosis (Mtb). Based on the results of mcfDNA sequencing, clinical presentation, and radiographic findings, a diagnosis of tuberculosis disease was made, and anti-tuberculosis treatment was initiated.

While awaiting results from acid-fast bacilli (AFB) cultures and molecular studies from sputum and tissue, plasma microbial cell-free DNA (mcfDNA) metagenomic sequencing was ordered on day 29 and was positive for Mycobacterium Tuberculosis (Mtb).

The patient was discharged on hospital day 60; 27 days after discharge, 58 days after the Mtb PCR resulted positive from tissue biopsy, and 60 days after the positive mcfDNA, sputum cultures returned positive for Mycobacterium tuberculosis.