Case Sudy Evolution of BDQ Resistance
Whole genome sequencing (WGS) based prediction of drug-resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens. We utilized WGS to investigate drug-resistant mutations in a 32-year-old Tanzanian male admitted to Kibong'oto Infectious Diseases Hospital (KIDH) with a history of interrupted MDR-TB treatments over three years. Before admission, he received various all-oral Bedaquiline-based MDR-TB treatment regimens with unfavourable outcomes. Drug susceptibility testing of serial M. tuberculosis isolates using MGIT culture and WGS revealed resistance to first-line anti-TB drugs, Bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS on serial cultured isolates identified the Beijing (Lineage 2.2.2) strain resistance against Bedaquiline, with mutations in the mmpR5 gene (Rv0678. An individualized regimen comprised of Bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reports no cough, chest pain, fever, or chest tightness, but still experiences numbness in his lower limbs. We propose the incorporation of WGS in the diagnostic framework for optimal management of DR and XDR-TB patients.