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Case Reports
. 2019 May 30;380(22):2178-2180.
doi: 10.1056/NEJMc1815121.

Bedaquiline Microheteroresistance after Cessation of Tuberculosis Treatment

Margaretha de Vos  1 , Serej D Ley  1 , Kristin B Wiggins  2 , Brigitta Derendinger  3 , Anzaan Dippenaar  3 , Melanie Grobbelaar  3 , Anja Reuter  4 , Tania Dolby  5 , Scott Burns  6 , Marco Schito  7 , David M Engelthaler  2 , John Metcalfe  8 , Grant Theron  3 , Annelies van Rie  9 , James Posey  6 , Rob Warren  10 , Helen Cox  11
Affiliations
Case Reports

Bedaquiline Microheteroresistance after Cessation of Tuberculosis Treatment

Margaretha de Vos et al. N Engl J Med. .
No abstract available

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Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of the manuscript.

Figures

Figure 1
Figure 1
Chronology of the diagnosis and treatment of the case study Summary of treatment provision, genotypic drug resistance (based on whole genome sequencing, WGS), phenotypic bedaquiline drug susceptibility testing (DST, MGIT), targeted deep sequencing and treatment monitoring during standardised treatment and a subsequent individualised bedaquilinecontaining regimen. Overall, eight isolates (A-H) collected 4.7 months after initiation of standard treatment regimen until 6 months after all TB treatment was stopped underwent WGS, targeted deep sequencing of Rv0678 and phenotypic bedaquiline DST. The patient was initially diagnosed with MDRTB with low-level isoniazid resistance using Genotype MTBDRplus, and treated with a standardised MDR-TB treatment regimen but remained culture positive. As per guidelines, subsequent isolates were phenotypically characterized for ofloxacin and amikacin susceptibility. Ofloxacin resistance was first noted 6 months after treatment initiation. All isolates remained susceptible to second-line injectables. At 8.1 months a revised regimen was initiated with the subsequent addition of bedaquiline (22 days after initiation of revised regimen) and withdrawal of pyrazinamide and ethambutol (2 months after initiation of revised regimen). Bedaquiline was administered for 6 months. The patient refused kanamycin at month 6 of the revised regimen for a duration of 2.4 months. The individualized regimen was continued until the outcome of treatment failure at 15 months. Phenotypic DST showed that all isolates with a variant frequency of >1% in Rv0678 were resistant to bedaquiline at 1µg/ml in MGIT. Abbreviations: MDR-TB=multi-drug resistant tuberculosis; INH=isoniazid; Z=pyrazinamide; KAN=kanamycin; MXF=moxifloxacin; ETH=ethionamide; TZD=terizidone; hdIND=high dose isoniazid; KAN=kanamycin; LZD=linezolid; E=ethambutol; PAS=para-aminosalicyclic acid; BDQ=bedaquiline; WGS=whole genome sequencing; DST=drug susceptibility testing; ins=insertion; R=resistant; S=susceptible
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References

    1. Schnippel K, Ndjeka N, Maartens G, et al. . Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study. The Lancet Respiratory medicine 2018;6:699-706. - PubMed
    1. Conradie F, Meintjes G, Hughes J, et al. . Clinical access to Bedaquiline Programme for the treatment of drug-resistant tuberculosis. S Afr Med J 2014;104:164-6. - PubMed
    1. Colman RE, Anderson J, Lemmer D, et al. . Rapid Drug Susceptibility Testing of Drug-Resistant Mycobacterium tuberculosis Isolates Directly from Clinical Samples by Use of Amplicon Sequencing: a Proof-of-Concept Study. Journal of clinical microbiology 2016;54:2058-67. - PMC - PubMed
    1. Andries K, Villellas C, Coeck N, et al. . Acquired resistance of Mycobacterium tuberculosis to bedaquiline. PloS one 2014;9:e102135. - PMC - PubMed
    1. McLeay SC, Vis P, van Heeswijk RP, Green B. Population pharmacokinetics of bedaquiline (TMC207), a novel antituberculosis drug. Antimicrobial agents and chemotherapy 2014;58:5315-24. - PMC - PubMed

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