High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates

Trisakul, Kanwara, Nonghanphithak, Ditthawat, Chaiyachat, Pratchakan, Kaewprasert, Orawee, Sakmongkoljit, Kankanon, Reechaipichitkul, Wipa, Chaiprasert, Angkana, Blair, David, Clark, Taane G., and Faksri, Kiatichai (2022) High clustering rate and genotypic drug-susceptibility screening for the newly recommended anti-tuberculosis drugs among global extensively drug-resistant Mycobacterium tuberculosis isolates. Emerging Microbes & Infections, 11 (1). pp. 1857-1866.

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Abstract

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) make TB difficult to control. Global susceptibility data for six newly recommended anti-TB drugs against M/XDR-TB are still limited. Using publicly available whole-genome sequences, we determined the proportion of 513 phenotypically XDR-TB isolates that carried mutations associated with resistance against these drugs (bedaquiline, clofazimine, linezolid, delamanid, pretomanid and cycloserine). Mutations of Rv0678 and Rv1979c were detected in 69/513 isolates (13.5%) for bedaquiline resistance and 79/513 isolates (15.4%) for clofazimine resistance with additional mmpL5 mutations. Mutations conferring resistance to delamanid were detected in fbiB and ddn genes for 11/513 isolates (2.1%). For pretomanid, a mutation was detected in the ddn gene for 3/513 isolates (0.6%). Nineteen mutations of pykA, cycA, ald, and alr genes, conferring resistance to cycloserine, were found in 153/513 isolates (29.8%). No known mutations associated with linezolid resistance were detected. Cluster analysis showed that 408/513 isolates fell within 99 clusters and that 354 of these isolates were possible primary drug-resistant TB (292 XDR-TB, 57 pre-XDR-TB and 5 MDR-TB). Clonal transmission of primary XDR isolates might contribute significantly to the high prevalence of DR-TB globally.

Item ID: 76595
Item Type: Article (Research - C1)
ISSN: 2222-1751
Keywords: bedaquiline, clofazimine, cycloserine, delamanid, linezolid, pretomanid, XDR-TB
Copyright Information: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Date Deposited: 24 Oct 2022 02:24
FoR Codes: 42 HEALTH SCIENCES > 4202 Epidemiology > 420207 Major global burdens of disease @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320211 Infectious diseases @ 50%
SEO Codes: 20 HEALTH > 2004 Public health (excl. specific population health) > 200404 Disease distribution and transmission (incl. surveillance and response) @ 100%
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