全基因组测序在治疗广泛耐药结核病中的临床应用:病例报告。

IF 4.6 2区 医学 Q1 MICROBIOLOGY
Bugwesa Z Katale, Sylvia Rofael, Linzy Elton, Erasto V Mbugi, Stella G Mpagama, Daphne Mtunga, Maryjesca G Mafie, Peter M Mbelele, Charlotte Williams, Happiness C Mvungi, Rachel Williams, Gulinja A Saku, Joanitha A Ruta, Timothy D McHugh, Mecky I Matee
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引用次数: 0

摘要

背景:基于全基因组测序(WGS)的结核分枝杆菌耐药性预测有望指导临床决策,从而设计出最佳治疗方案:基于全基因组测序(WGS)的结核分枝杆菌耐药性预测有望在设计最佳治疗方案时为临床决策提供指导:我们利用 WGS 调查了一名入住 Kibong'oto 传染病医院的 32 岁坦桑尼亚男性患者的耐药性突变,该患者曾中断耐多药结核病治疗三年多。入院前,他曾接受过多种全口服贝达喹啉的耐多药结核病治疗方案,但疗效不佳:结果:使用分枝杆菌生长培养基试管培养和 WGS 对系列结核杆菌分离株进行药敏试验,发现其对一线抗结核药物、贝达喹啉和氟喹诺酮类药物耐药,但对利奈唑胺、氯法齐明和地拉那米德敏感。对连续培养的分离株进行的 WGS 发现,北京(2.2.2 系)菌株对贝达喹啉耐药,其 mmpR5 基因(Rv0678.这项研究还揭示了对贝达喹啉耐药的结核菌株中出现了两个不同的亚群,它们的 mmpR5 基因分别发生了 Asp47f 和 Glu49fs 框移突变,这可能是导致耐药时间延长的根本原因。我们设计了一套个性化的治疗方案,包括贝达喹啉、地拉米尼、吡嗪酰胺、乙硫异烟胺和对氨基水杨酸。患者在第 8 个月出院回家,目前已是治疗的第 9 个月。他没有出现咳嗽、胸痛、发烧或胸闷等症状,但下肢仍有麻木感:我们建议将 WGS 纳入诊断框架,以优化耐药和广泛耐药结核病患者的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical application of whole-genome sequencing in the management of extensively drug-resistant tuberculosis: a case report.

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.

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来源期刊
CiteScore
8.60
自引率
0.00%
发文量
49
审稿时长
>12 weeks
期刊介绍: Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.
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