Whole-genome sequencing for surveillance of tuberculosis drug resistance and determination of resistance level in China

Liu, Dongxin; Huang, Fei; Zhang, Guoliang; He, Wencong; Ou, Xichao; He, Ping; Zhao, Bing; Zhu, Baoli; Liu, Fei; Li, Zhiyuan; Liu, Chunfa; Xing, Hui; Wang, Shengfen; Zhou, Yang; Walker, Timothy M.; Liu, Lei; Crook, Derrick W.; Zhao, Yanlin

doi:10.1016/j.cmi.2021.09.014

Cited by 41 publications

(35 citation statements)

References 24 publications

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“…29 This breakpoint artifact has been also observed in a study in China which used quantitative Sensititre MYCOTB plates. 30 Also, different mutations in gyrB at amino acid positions 499-501 (the quinolone binding pocket) exhibit variable effects on the resistance level to different fluoroquinolones, in line with a previous study. 31 We also confirmed results of other studies suggesting that the gyrB Glu501Asp mutation confers resistance to moxifloxacin but not to levofloxacin at the currently endorsed critical concentrations.…”

Section: Discussionsupporting

confidence: 87%

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Finci¹,

Albertini²,

Merker³

et al. 2022

The Lancet Microbe

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Section: Discussionsupporting

confidence: 87%

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Finci¹,

Albertini²,

Merker³

et al. 2022

The Lancet Microbe

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“…Previous studies have shown that the proportion of borderline rpoB mutations in rifampicin-resistant Mycobacterium tuberculosis isolates, ranging from 3.3% to 13.1%. 3 , 10–12 The reported proportion of 20.4% in china 7 is higher than other countries. This study provided evidence that only 43.9% of rifampicin resistance conferred by borderline mutation was detected by L-J medium-based DST at the critical concentration of 40.0μg/mL 6 with 4-week incubation.…”

Section: Discussionmentioning

confidence: 88%

“…In china, borderline rpoB mutations accounted for 20.4% of the total rpoB mutations detected. 7 Regarding the higher prevalence of borderline rpoB mutations and commonly used phenotypic DSTs in China, the ability of L-J medium-based DST to detect borderline rifampicin resistance conferred by specific mutations was explored in comparison with molecular based Xpert MTB/RIF.…”

Section: Introductionmentioning

confidence: 99%

Detection of Mycobacterium tuberculosis Rifampicin Resistance Conferred by Borderline rpoB Mutations: Xpert MTB/RIF is Superior to Phenotypic Drug Susceptibility Testing

Xing¹,

Song²,

Zheng³

et al. 2022

IDR

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Objective To compare the ability of detection of borderline rifampicin resistance in Mycobacterium tuberculosis between molecular assay and phenotypic drug susceptibility tests. Methods Fifty-seven isolates with His445Leu, Asp435Tyr, Leu452Pro, Leu430Pro, His445Asn, Ile491Phe, and His445Ser mutations in rpoB gene identified by whole-genome sequencing conferring borderline rifampicin resistance were included. Molecular-based Xpert MTB/RIF, phenotypic Löwenstein–Jensen (L-J) medium-based drug susceptibility test (DST) with a critical concentration of 40.0μg/mL and minimal inhibitory concentration (MIC) assay were performed to detect borderline rifampicin resistance. Results When using Xpert MTB/RIF, 48/57 (84.2%) isolates exhibited resistance to rifampicin. 25/57 (43.9%) and 33/57 (57.9%) isolates showed rifampicin resistance by L-J medium-based DST with 4 and 6 weeks of incubation, respectively. 30/57 (52.6%) and 40/57 (70.2%) strains were resistant to rifampicin by MIC method at cutoff values of 1.0 and 0.5μg/mL, respectively. The detection rate of rifampicin resistance of Xpert MTB/RIF was significantly higher than that of phenotypic methods ( p < 0.001). Of the 57 isolates with borderline rpoB mutations, 5 (8.8%) had MICs of 0.25 or 0.12μg/mL, 22 (38.6%) had MICs of 0.5μg/mL or 1.0μg/mL, and 30 (52.6%) other isolates showed MICs ≥2.0μg/mL. Conclusion Molecular-based Xpert MTB/RIF showed superior ability to detect borderline rifampicin resistance over phenotypic DST methods. Extending the incubation time of L-J DST or lowering the cutoff value of the MIC method can improve borderline rifampicin resistance detection.

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“…However, in this study, we collected sputum from patients on a continuous basis and performed pictures and cultures, which explained the low bacteriological examination. This is a common problem in most tuberculosis outbreak investigations, which has limited our understanding of the whole transmission network ( 30 ). Second, we did not follow those students who received preventive therapy for a long enough time.…”

Section: Discussionmentioning

confidence: 99%

A university-clustered tuberculosis outbreak during the COVID-19 pandemic in eastern China

Zhu

Yu³

et al. 2022

Front. Public Health

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During the COVID-19 pandemic in 2020, a tuberculosis outbreak occurred in a university in eastern China, with 4,488 students and 421 staff on the campus. A 19-year-old student was diagnosed in August 2019. Later, the first round of screening was initiated among close contacts, but no active cases were found. Till September 2020, four rounds of screening were performed. Four rounds of screening were conducted on September 9, November 8, November 22-25 in 2019 and September 2020, with 0, 5, 0 and 43 cases identified, respectively. A total of 66 active tuberculosis were found in the same university, including 4 sputum culture-positive and 7 sputum smear-positive. The total attack rate of active tuberculosis was 1.34% (66/4909). The whole-genome sequencing showed that the isolates belonged to the same L2 sub-specie and were sensitive to all tested antituberculosis drugs. Delay detection, diagnosis and report of cases were the major cause of this university tuberculosis epidemic. More attention should be paid to the asymptomatic students in the index class. After the occurrence of tuberculosis cases in schools, multiple rounds of screening should be carried out, and preventive therapy should be applied in a timely manner.

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Whole-genome sequencing for surveillance of tuberculosis drug resistance and determination of resistance level in China

Cited by 41 publications

References 24 publications

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Investigating resistance in clinical Mycobacterium tuberculosis complex isolates with genomic and phenotypic antimicrobial susceptibility testing: a multicentre observational study

Detection of Mycobacterium tuberculosis Rifampicin Resistance Conferred by Borderline rpoB Mutations: Xpert MTB/RIF is Superior to Phenotypic Drug Susceptibility Testing

A university-clustered tuberculosis outbreak during the COVID-19 pandemic in eastern China

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