Clinical application of whole-genome sequencing in the management of extensively drug-resistant tuberculosis: a case report.
Humans
Male
Adult
Whole Genome Sequencing
Extensively Drug-Resistant Tuberculosis
/ drug therapy
Antitubercular Agents
/ therapeutic use
Mycobacterium tuberculosis
/ genetics
Microbial Sensitivity Tests
Drug Resistance, Multiple, Bacterial
/ genetics
Tanzania
Mutation
Diarylquinolines
/ therapeutic use
Genome, Bacterial
Linezolid
/ therapeutic use
Case Report
Clinical application
Genomic Diagnostics
Whole-genome sequencing
XDR-TB
Journal
Annals of clinical microbiology and antimicrobials
ISSN: 1476-0711
Titre abrégé: Ann Clin Microbiol Antimicrob
Pays: England
ID NLM: 101152152
Informations de publication
Date de publication:
22 Aug 2024
22 Aug 2024
Historique:
received:
31
05
2024
accepted:
11
08
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
Whole-genome sequencing (WGS)-based prediction of drug resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens. We utilized WGS to investigate drug resistance mutations in a 32-year-old Tanzanian male admitted to Kibong'oto Infectious Diseases Hospital with a history of interrupted multidrug-resistant tuberculosis treatment for more than three years. Before admission, he received various all-oral bedaquiline-based multidrug-resistant tuberculosis treatment regimens with unfavourable outcomes. Drug susceptibility testing of serial M. tuberculosis isolates using Mycobacterium Growth Incubator Tubes culture and WGS revealed resistance to first-line anti-TB drugs, bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS of serial cultured isolates revealed that the Beijing (Lineage 2.2.2) strain was resistant to bedaquiline, with mutations in the mmpR5 gene (Rv0678. This study also revealed the emergence of two distinct subpopulations of bedaquiline-resistant tuberculosis strains with Asp47f and Glu49fs frameshift mutations in the mmpR5 gene, which might be the underlying cause of prolonged resistance. An individualized regimen comprising bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reported no cough, chest pain, fever, or chest tightness but still experienced numbness in his lower limbs. We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.
Sections du résumé
BACKGROUND
BACKGROUND
Whole-genome sequencing (WGS)-based prediction of drug resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens.
METHODS
METHODS
We utilized WGS to investigate drug resistance mutations in a 32-year-old Tanzanian male admitted to Kibong'oto Infectious Diseases Hospital with a history of interrupted multidrug-resistant tuberculosis treatment for more than three years. Before admission, he received various all-oral bedaquiline-based multidrug-resistant tuberculosis treatment regimens with unfavourable outcomes.
RESULTS
RESULTS
Drug susceptibility testing of serial M. tuberculosis isolates using Mycobacterium Growth Incubator Tubes culture and WGS revealed resistance to first-line anti-TB drugs, bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS of serial cultured isolates revealed that the Beijing (Lineage 2.2.2) strain was resistant to bedaquiline, with mutations in the mmpR5 gene (Rv0678. This study also revealed the emergence of two distinct subpopulations of bedaquiline-resistant tuberculosis strains with Asp47f and Glu49fs frameshift mutations in the mmpR5 gene, which might be the underlying cause of prolonged resistance. An individualized regimen comprising bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reported no cough, chest pain, fever, or chest tightness but still experienced numbness in his lower limbs.
CONCLUSION
CONCLUSIONS
We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.
Identifiants
pubmed: 39175078
doi: 10.1186/s12941-024-00737-9
pii: 10.1186/s12941-024-00737-9
doi:
Substances chimiques
Antitubercular Agents
0
bedaquiline
78846I289Y
Diarylquinolines
0
Linezolid
ISQ9I6J12J
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
76Informations de copyright
© 2024. The Author(s).
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