A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

Autor: Pinhata JMW; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil. juliana.pinhata@ial.sp.gov.br., Ferrazoli L; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil., Mendes FF; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil., Gonçalves MG; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil., Rabello MCDS; Fundação Oswaldo Cruz (FIOCRUZ), Centro de Pesquisas Aggeu Magalhães, Recife, PE, Brazil., Ghisi KT; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil., Simonsen V; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil., Cavalin RF; Instituto de Infectologia Emílio Ribas (IIER), São Paulo, SP, Brazil., Lindoso AABP; Instituto de Infectologia Emílio Ribas (IIER), São Paulo, SP, Brazil., de Oliveira RS; Núcleo de Tuberculose e Micobacterioses, Centro de Bacteriologia, Instituto Adolfo Lutz (IAL), Av. Dr. Arnaldo, 351, 9º Andar, São Paulo, SP, 01246-000, Brazil.
Jazyk: angličtina
Zdroj: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology [Eur J Clin Microbiol Infect Dis] 2024 Jan; Vol. 43 (1), pp. 73-85. Date of Electronic Publication: 2023 Nov 09.
DOI: 10.1007/s10096-023-04693-8
Abstrakt: Purpose: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil.
Methods: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB.
Results: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes.
Conclusion: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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