Genetic factors associated with acquired phenotypic drug resistance and its compensatory evolution during tuberculosis treatment.
Clin Microbiol Infect
; 30(5): 637-645, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38286176
ABSTRACT
OBJECTIVES:
We elucidated the factors, evolution, and compensation of antimicrobial resistance (AMR) in Mycobacterium tuberculosis (MTB) isolates under dual pressure from the intra-host environment and anti-tuberculosis (anti-TB) drugs.METHODS:
This retrospective case-control study included 337 patients with pulmonary tuberculosis from 15 clinics in Tianjin, China, with phenotypic drug susceptibility testing results available for at least two time points between January 1, 2009 and December 31, 2016. Patients in the case group exhibited acquired AMR to isoniazid (INH) or rifampicin (RIF), while those in the control group lacked acquired AMR. The whole-genome sequencing (WGS) was conducted on 149 serial longitudinal MTB isolates from 46 patients who acquired or reversed phenotypic INH/RIF-resistance during treatment. The genetic basis, associated factors, and intra-host evolution of acquired phenotypic INH/RIF-resistance were elucidated using a combined analysis.RESULTS:
Anti-TB interruption duration of ≥30 days showed association with acquired phenotypic INH/RIF resistance (aOR = 2·2, 95% CI, 1·0-5·1) and new rpoB mutations (p = 0·024). The MTB evolution was 1·2 (95% CI, 1·02-1·38) single nucleotide polymorphisms per genome per year under dual pressure from the intra-host environment and anti-TB drugs. AMR-associated mutations occurred before phenotypic AMR appearance in cases with acquired phenotypic INH (10 of 16) and RIF (9 of 22) resistances.DISCUSSION:
Compensatory evolution may promote the fixation of INH/RIF-resistance mutations and affect phenotypic AMR. The TB treatment should be adjusted based on gene sequencing results, especially in persistent culture positivity during treatment, which highlights the clinical importance of WGS in identifying reinfection and AMR acquisition before phenotypic drug susceptibility testing.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Rifampina
/
Tuberculose Pulmonar
/
Sequenciamento Completo do Genoma
/
Isoniazida
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Mycobacterium tuberculosis
/
Antituberculosos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
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Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Microbiol Infect
Assunto da revista:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China