Prevalence of extensively drug-resistant tuberculosis in a Chinese multidrug-resistant TB cohort after redefinition

Xuxia Zhang,Tongxin Li,Yufeng Wang,Liang Li,Lu Wang,Haiping Guo,Qiang Li,Cong Yao,Yuanyuan Shang,Yu Pang,Zhongtan Xue

doi:10.1186/s13756-021-00995-8

Abstract

ObjectivesRecently, the definition of extensively drug-resistant TB (XDR-TB) has been revised. In this study, we conducted a descriptive and retrospective study to determine the prevalence of XDR-TB in a Chinese multidrug-resistant TB (MDR-TB) cohort.MethodsBroth microdilution method was performed to determine in vitro susceptibilities of Mycobacterium tuberculosis (MTB) isolates to (FQs), bedaquiline (BDQ) and linezolid (LZD). The putative drug target genes conferring drug resistance were screened by DNA sequencing.ResultsA total of 425 MDR-TB isolates were included from 13 pilots in China. LZD and BDQ resistance were noted in 30 (7.1%) and 10 (2.4%) isolates. On the basis of latest definitions, 114 (26.8%) were MDR-TB, 282 (66.4%) were pre-XDR-TB, and 29 (6.8%) were XDR-TB. Among 311 FQ-resistant isolates, 265 harbored genetic mutations within QRDRs. The most common mutations were observed at codon 94 of gyrA, accounting for 47.2% of FQ-resistant MTB isolates. Only mutations within the Rv0678 gene were found to confer BDQ resistance in our cohort, conferring 40.0% of BDQ resistance. For LZD resistance, 53.3% of LZD-resistant isolates carried genetic mutations in rplC or 23S rRNA. The most frequent mutation was Cys154Arg in the rplC gene. In addition, we recorded two MDR-TB patients with resistance to both BDQ and LZD, of which one patient experienced continuous positive culture of MTB despite inclusion of efficacious moxifloxacin.ConclusionOur results demonstrate that the low prevalence of XDR-TB holds great promise for MDR-TB treatment with WHO-endorsed regimens containing BDQ-LZD combination, whereas the high prevalence of FQ-resistance in MDR-TB patients warrants national attention.

Highlights

Tuberculosis, caused by Mycobacterium tuberculosis (MTB) complex, continues to be a global public health priority [1, 2]
Bacterial isolates Between February 2018 and June 2019, a retrospective cohort study was conducted by inclusion of multidrug-resistant tuberculosis (MDR-TB) patients in 13 hospitals, aiming to determine clinical efficacy of MDR-TB patients treated with BDQ-containing regimens [18]
The positive cultures were stored in 7H9 medium supplemented with 10% of oleic acid-albumin-dextrose-catalase (OADC) and 5% glycerol. prior to determining minimum inhibitory concentration (MIC) values, the isolates were recovered on Löwenstein–Jensen (L–J) medium for 4 weeks at 37 °C

Summary

Introduction

Tuberculosis, caused by Mycobacterium tuberculosis (MTB) complex, continues to be a global public health priority [1, 2]. The emergence of multidrug-resistant tuberculosis (MDR-TB; resistant to at least isoniazid and rifampin), with an estimated burden of 78%. Because of inherent resistance to the two most potent anti-TB drugs, MDR-TB treatment requires the use of second-line drugs that are less effective, more toxic, and costlier than first-line regimens [4, 5]; the overall rate of treatment success among MDR-TB patients is currently 57% [1]. This unsatisfactory outcome is expected to worsen the epidemic of this severe form of TB. More efforts are urgently needed for new and effective drugs to improve the chemotherapy of MDR-TB [6]

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