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Journal Article > Research

MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era

Beckert P, Sanchez-Padilla E, Merker M, Dreyer V, Kohl TA, Utpatel C, Koser CU, Barilar I, Ismail N, Omar SV, Klopper M, Warren RM, Hoffmann H, Maphalala G, Ardizzoni E, de Jong BC, Kerschberger B, Schramm B, Andres S, Kranzer K, Maurer FP, Bonnet MMB, Niemann S
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Abstract
Background
Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini.

Methods
We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017).

Results
MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2.

Conclusion
The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.
Subject Area
tuberculosisoutbreaks
DOI
10.1186/s13073-020-00793-8
Published Date
25-Nov-2020
PubMed ID
33239092
Languages
English
Journal
Genome Medicine
Volume / Issue / Pages
Volume 12
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