Journal article
Sources of multidrug resistance in patients with previous isoniazid-resistant tuberculosis identified using whole genome sequencing: A longitudinal cohort study
- Abstract:
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Background Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB.
Methods Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs.
Results Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate.
Conclusions In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Supplementary materials, 31.2KB, Terms of use)
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- Publisher copy:
- 10.1093/cid/ciaa254
Authors
- Publisher:
- Oxford University Press
- Journal:
- Clinical Infectious Diseases More from this journal
- Volume:
- 71
- Issue:
- 10
- Pages:
- e532–e539
- Publication date:
- 2020-03-13
- Acceptance date:
- 2020-03-10
- DOI:
- EISSN:
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1537-6591
- ISSN:
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1058-4838
- Pmid:
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32166306
- Language:
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English
- Keywords:
- Pubs id:
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1093669
- Local pid:
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pubs:1093669
- Deposit date:
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2020-06-18
Terms of use
- Copyright holder:
- Srinivasan et al.
- Copyright date:
- 2020
- Rights statement:
- © The Authors 2020. Published by Oxford University Press for the Infectious Diseases Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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