Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study
| Autor: | Do Dang Anh Thu, Dang T M Ha, Sarah J. Dunstan, Nguyen Phu Huong Lan, Maxine Caws, Philip Ashton, Guy E. Thwaites, Vijay Srinivasan, Vu T. N. Ha, Dao N. Vinh, Hoang T. Hai, Timothy M Walker, Nguyen Thuy Thuong Thuong, Phan Vuong Khac Thai |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) medicine.medical_specialty Tuberculosis wa_950 030106 microbiology Antitubercular Agents Single-nucleotide polymorphism Disease Microbial Sensitivity Tests Major Articles qw_45 Mycobacterium tuberculosis 03 medical and health sciences multidrug resistance Internal medicine Tuberculosis Multidrug-Resistant medicine Isoniazid Humans Longitudinal Studies Online Only Articles Whole genome sequencing whole genome sequencing biology business.industry rifampicin resistance Isoniazid resistance biology.organism_classification medicine.disease Multiple drug resistance isoniazid resistance 030104 developmental biology Infectious Diseases AcademicSubjects/MED00290 tuberculosis qu_550 wf_200 business medicine.drug |
| Zdroj: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 |
| Popis: | 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. We investigated the sources of multidrug-resistant (MDR) tuberculosis (TB) in patients with isoniazid-resistant TB treated with first-line anti-TB therapy and show that reinfection with a new MDR-TB strain was just as common as the emergence of rifampicin resistance among these patients. |
| Databáze: | OpenAIRE |
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