Emergence and characterisation of bedaquiline, pretomanid and linezolid resistance in recurrent rifampicin-resistant tuberculosis patient: A case report
- 1Department of Pathology School of Medicine, University of Limpopo, South Africa
- 2Microbiology Department, Polokwane Laboratory, National Health Laboratory Service, Polokwane, South Africa
- 3MDR-TB Unit, FH Odendaal Hospital, Limpopo Department of Health, South Africa
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.
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BibTeX
@article{kaapu2026emergence,
title = {{Emergence and characterisation of bedaquiline, pretomanid and linezolid resistance in recurrent rifampicin-resistant tuberculosis patient: A case report}},
author = {Kabelo Gabriel Kaapu and Ramathetje Virginia Ntsoane and Casious Raphiri and Molebogeng Ruth Lekalakala-Mokaba and Ivy Rukasha},
journal = {IDCases},
year = {2026},
month = oct,
doi = {10.1016/j.idcr.2026.e02817},
url = {https://doi.org/10.1016/j.idcr.2026.e02817},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Emergence and characterisation of bedaquiline, pretomanid and linezolid resistance in recurrent rifampicin-resistant tuberculosis patient: A case report
AU - Kabelo Gabriel Kaapu
AU - Ramathetje Virginia Ntsoane
AU - Casious Raphiri
AU - Molebogeng Ruth Lekalakala-Mokaba
AU - Ivy Rukasha
PY - 2026
DA - 2026/10/24
JO - IDCases
DO - 10.1016/j.idcr.2026.e02817
UR - https://doi.org/10.1016/j.idcr.2026.e02817
AB - 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.
SN - 2214-2509
ER -