Abstract
Mycobacterium tuberculosis primarily causes pulmonary disease but can involve extrapulmonary sites, including bones and joints. Tuberculosis (TB) prosthetic joint infections (TB-PJIs) are rare, often diagnosed late due to low suspicion, indolent progression, and frequent culture negativity. A 73-year-old man from Guyana underwent elective right total knee arthroplasty for osteoarthritis. Postoperatively, he developed a prosthetic joint infection without an identifiable pathogen by routine cultures. Advanced testing detected Mycobacterium tuberculosis complex via next-generation 16S rRNA gene sequencing. The patient initially improved with RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) therapy but subsequently developed disseminated disease, raising concern for suspected drug-resistant TB. His hospital course was further complicated by bladder rupture and multiorgan failure, leading to death. TB-PJIs may present without pulmonary symptoms or prior TB history and should be suspected in culture-negative joint infections, particularly when conventional therapy fails. Treatment may be further complicated by suspected multidrug resistance, as illustrated in this case.