Bedaquiline Resistance after Effective Treatment of Multidrug-Resistant Tuberculosis, Namibia

Abstract

Bedaquiline is currently a key drug for treating multidrug-resistant or rifampin-resistant tuberculosis. We report and discuss the unusual development of resistance to bedaquiline in a teenager in Namibia, despite an optimal background regimen and adherence. The report highlights the risk for bedaquiline resistance development and the need for rapid drug-resistance testing.

Keywords: MDR TB; Namibia; TB; antimicrobial resistance; bacteria; bedaquiline; respiratory infections; tuberculosis; tuberculosis and other mycobacteria.

Figure 1

Chest radiographs showing lungs of patient in Namibia who developed bedaquiline resistance. A) At treatment initiation; B) at culture conversion; C) 3 months after conversion.

Figure 2

Timeline for a case of tuberculosis in a patient in Namibia whose infection became drug resistant after effective treatment. The case was originally diagnosed and treated beginning in December 2021. Interruptions in treatment were caused by stockout. Second-line drugs were not used. Full detailed treatment history is unknown. The patient sought care in Namibia in September 2022; we diagnosed MDR TB in October 2022. Treatment failed and rv0678 mutation was identified in a culture from June 2023. A) Patient’s treatment history. Green bars represent treatment of drug-susceptible TB; blue bars represent treatment of MDR TB. B) Evolution of phenotypic and genotypic drug susceptibility testing with resistance-associated variants using Deeplex Myc TB (https://www.deeplex.com). Testing was done at time of diagnosis of MDR TB and after culture reversion. Bold text de novo indicates mutations. Months show time of specimen collection. C) Culture and smear test results. Asterisks indicate that tests were not done because of stockouts. Months show time of specimen collection. Dagger indicates start of MDR TB treatment. AMI, amikacin; BDQ, bedaquiline; CFZ, clofazimine; CS, cycloserine; DS, drug-susceptible; EMB, ethambutol; FQ, fluoroquinolones; INH, isoniazid; LIN, linezolid; LFX, levofloxacin; MDR, multidrug-resistant; ND, not done; PYR, pyrazinamide; R, resistant; RIF, rifampin; S, susceptible; TB, tuberculosis; WT, wild type.