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Emergence and characterisation of bedaquiline, pretomanid and linezolid resistance in recurrent rifampicin-resistant tuberculosis patient: A case report

Year: 2026

Type: article

Abstract: Background Bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD)-based (BPaL) regimens have transformed rifampicin-resistant tuberculosis (RR-TB) treatment. However, resistance to these drugs is increasingly reported, while longitudinal data integrating clinical, phenotypic and genomic evolution remain limited. Case presentation We report a fatal case of recurrent RR-TB in a 40-year-old South African woman with HIV infection who received BPaL therapy. Following treatment completion, recurrent disease was complicated by pregnancy, treatment interruption and loss to follow-up. She subsequently re-presented with advanced cavitary pulmonary tuberculosis and respiratory failure. Despite re-initiation of BPaL, she deteriorated and died from septic shock. Routine drug susceptibility testing, available posthumously, confirmed resistance to BDQ, Pa and LZD. Seven sequential Mycobacterium tuberculosis isolates collected during treatment underwent minimum inhibitory concentration (MIC) testing and whole-genome sequencing. All demonstrated phenotypic resistance to the three BPaL drugs. Serial genomic analysis identified progressive Rv0678 diversification associated with a two-fold increase in BDQ MIC, while resistance-associated rrl and fbiC mutations remained comparatively stable despite persistently elevated LZD and Pa MICs. Conclusions This case demonstrates the interaction of treatment interruption, delayed resistance detection and continued within-host bacterial adaptation during BPaL therapy. Longitudinal phenotypic and genomic findings revealed distinct resistance trajectories among BPaL drugs, highlighting the importance of treatment retention, timely susceptibility testing and genomic surveillance for preserving BPaL effectiveness.

Source: IDCases

DOI: 10.1016/j.idcr.2026.e02817

Authors: Kabelo Gabriel Kaapu, Ramathetje Virginia Ntsoane, Casious Raphiri, Molebogeng Ruth Lekalakala-Mokaba, Ivy Rukasha

Institutions: University of Limpopo, National Health Laboratory Service, Department of Health

Language: English

Topic: Tuberculosis Research and Epidemiology

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,370