Clinical application of whole-genome sequencing in the management of extensively drug-resistant tuberculosis: a case report.

Autor: Katale BZ; Tanzania Commission for Science and Technology (COSTECH), P.O. BOX 4302, Dar es Salaam, Tanzania. bugwesa2002@yahoo.co.uk., Rofael S; Centre for Clinical Microbiology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2QG, UK.; Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Elton L; Centre for Clinical Microbiology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2QG, UK., Mbugi EV; Department of Biochemistry and Molecular Biology, Muhimbili University of Health and Allied Sciences (MUHAS), P.O. BOX 65001, Dar es Salaam, Tanzania., Mpagama SG; Kibong'oto Infectious Diseases Hospital (KIDH), P.O. BOX 12, Mae Street, Siha, Kilimanjaro, Tanzania., Mtunga D; Central Tuberculosis Reference Laboratory, National Tuberculosis and Leprosy Programme, Muhimbili National Hospital, P.O Box 65000, Dar es Salaam, Tanzania., Mafie MG; Central Tuberculosis Reference Laboratory, National Tuberculosis and Leprosy Programme, Muhimbili National Hospital, P.O Box 65000, Dar es Salaam, Tanzania., Mbelele PM; Kibong'oto Infectious Diseases Hospital (KIDH), P.O. BOX 12, Mae Street, Siha, Kilimanjaro, Tanzania.; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), P.O. BOX 65001, Dar es Salaam, Tanzania., Williams C; Centre for Clinical Microbiology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2QG, UK., Mvungi HC; Kibong'oto Infectious Diseases Hospital (KIDH), P.O. BOX 12, Mae Street, Siha, Kilimanjaro, Tanzania., Williams R; Centre for Clinical Microbiology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2QG, UK., Saku GA; Kibong'oto Infectious Diseases Hospital (KIDH), P.O. BOX 12, Mae Street, Siha, Kilimanjaro, Tanzania., Ruta JA; Kibong'oto Infectious Diseases Hospital (KIDH), P.O. BOX 12, Mae Street, Siha, Kilimanjaro, Tanzania., McHugh TD; Centre for Clinical Microbiology, University College London (UCL), Royal Free Campus, Rowland Hill Street, London, NW3 2QG, UK., Matee MI; Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences (MUHAS), P.O. BOX 65001, Dar es Salaam, Tanzania.
Jazyk: angličtina
Zdroj: Annals of clinical microbiology and antimicrobials [Ann Clin Microbiol Antimicrob] 2024 Aug 22; Vol. 23 (1), pp. 76. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1186/s12941-024-00737-9
Abstrakt: 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: 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: 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: We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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