Molecular characterisation of extensively drug-resistant Mycobacterium tuberculosis isolates in China

Zhao, Lili; Sun, Qing; Zeng, Chunyan; Chen, Yan; Zhao, Bing; Liu, Haican; Xia, Qiang; Zhao, Xiuqin; Jiao, Weiwei; Li, Guilian; Wan, Kanglin

doi:10.1016/j.ijantimicag.2014.09.018

Cited by 13 publications

(12 citation statements)

References 29 publications

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“…Other genes, such as gidB , should be included for detecting SM resistance. The mutation rate of CAP- or KAN-resistant isolates was 100.0%, significantly higher than the prior data 7,9,15,30. Furthermore, no mutation occurred within sequenced tlyA and eis loci, which might be owing to the small number of CAP- or KAN-resistant isolates in this study.…”

Section: Discussioncontrasting

confidence: 69%

“…Genomic DNA was prepared using the CTAB method as described by Somerville et al12 Strain differentiation was performed with spoligotyping as described by Kamerbeek et al13 Further genotyping of Beijing family strains was done according to the presence or absence of IS6110 in the noise transfer function (NTF) region as described previously 14,15. Modern Beijing strains inserted in the NTF region yielded 1500 bp PCR products, while ancient Beijing strains without insertions yielded 300 bp PCR products.…”

Section: Methodsmentioning

confidence: 99%

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<p>Prevalence, risk and genetic characteristics of drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China</p>

Zhao¹,

Huang²,

Xiao³

et al. 2019

IDR

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Objectives To explore the prevalence, risk and genetic characteristics of drug-resistant tuberculosis (TB) from a tertiary care TB hospital in China. Patients and methods We carried out a retrospective study including isolates from 189 patients with pulmonary TB at Fuzhou Pulmonary Hospital. All isolates from these patients were subjected to drug susceptibility testing and genotyping. For drug-resistant isolates, DNA sequencing was used to investigate mutations in 12 loci, including katG , inhA , oxyR–ahpC , rpoB , rpsL , rrs 1 (nucleotides 388–1084 of rrs), embB , tlyA , eis , rrs 2 (nucleotides 1158–1674 of rrs), gyrA and gyrB . Results Among 189 isolates, 28.6% were resistant to at least one of the seven anti-TB drugs, including isoniazid (INH), rifampin (RIF), streptomycin (STR), ethambutol (EMB), capreomycin (CAP), kanzmycin (KAN) and ofloxacin (OFX). The proportion of multidrug-resistant TB and extensively drug-resistant TB isolates was 9.5% and 1.1%, respectively. Patients in rural areas as well as previously treated patients showed a significantly increased risk of developing drug resistance. In addition, among these isolates, 111 (58.7%) were Beijing genotype strains, 84 (75.7%) of which belonged to modern Beijing sublineage. There was no association between genotype and drug resistance. The most common mutations were katG 315, rpo B 531 rpsL 43, embB 306, rrs 1401 and gyrA 94. Conclusion These findings provided additional information of drug-resistant TB in China. Previously treated patients and patients in rural areas should receive greater attention owing to their higher risk of developing drug resistance.

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Section: Discussioncontrasting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

<p>Prevalence, risk and genetic characteristics of drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China</p>

Zhao¹,

Huang²,

Xiao³

et al. 2019

IDR

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“…In this study, the most common mutations in gyrA were found in the QRDR at positions 94, 90, and 91, carried by 62% OFX mono‐resistant MTB isolates, which was in agreement with the previously findings from literatures . To our knowledge, this is the first report to show that the mutations T539A and E540D in the QRDR in gyrB were found from OFX mono‐resistant MTB isolates in China.…”

Section: Discussionsupporting

confidence: 92%

Molecular characteristics of ofloxacin mono‐resistant Mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients

ZhiRui

Xie

et al. 2017

Clinical Laboratory Analysis

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Background Ofloxacin (OFX) resistant Mycobacterium tuberculosis (MTB) isolates have been increasingly observed and are a major concern in recent years. This study investigated the genetic mutations associated with OFX resistance among clinical OFX mono‐resistant MTB isolates from new and previously treated tuberculosis patients. Methods A total of 50 unrelated OFX mono‐resistant MTB isolates were analyzed. For all isolates, the quinolone resistance determining regions of gyrA and gyrB were PCR amplified and sequenced. Results Single mutations in the quinolone resistance determining regions of gyrA (positions D94A, G, N, and Y; A90V; and S91P) and gyrB (positions T539A and E540D) were observed in 62% (31/50) and 4% (2/50) of all OFX mono‐resistant isolates, respectively. No differences were detected between the proportions of isolates with mutations in gyrA/gyrB from new and previously treated tuberculosis patients (P=.820). Conclusions Although mutations in gyrB were rare, they were as important as mutations in gyrA in predicting OFX resistance in MTB in Tianjin, China.

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“…The fact that four different amino acid changes had been observed at the gyrB codon in question (T500A/I/N/P) constitutes a potential signal for drug selection (7, 34, 35). In line with this observation, allelic exchange experiments with T500N in an Erdman background increased the MIC from wild-type levels to the CC for OFX and LFX and just above the CC for MFX (36).…”

Section: Discussionmentioning

confidence: 99%

Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin

Wang

Chen

et al. 2016

Antimicrob Agents Chemother

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f Antofloxacin (AFX) is a novel fluoroquinolone that has been approved in China for the treatment of infections caused by a variety of bacterial species. We investigated whether it could be repurposed for the treatment of tuberculosis by studying its in vitro activity. We determined the wild-type and non-wild-type MIC ranges for AFX as well as ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MFX), using the microplate alamarBlue assay, of 126 clinical Mycobacterium tuberculosis strains from Beijing, China, of which 48 were OFX resistant on the basis of drug susceptibility testing on Löwenstein-Jensen medium. The MIC distributions were correlated with mutations in the quinolone resistance-determining regions of gyrA (Rv0006) and gyrB (Rv0005). Pharmacokinetic/pharmacodynamic (PK/PD) data for AFX were retrieved from the literature. AFX showed lower MIC levels than OFX but higher MIC levels than LFX and MFX on the basis of the tentative epidemiological cutoff values (ECOFFs) determined in this study. All strains with non-wild-type MICs for AFX harbored known resistance mutations that also resulted in non-wild-type MICs for LFX and MFX. Moreover, our data suggested that the current critical concentration of OFX for Löwenstein-Jensen medium that was recently revised by the World Health Organization might be too high, resulting in the misclassification of phenotypically non-wildtype strains with known resistance mutations as wild type. On the basis of our exploratory PK/PD calculations, the current dose of AFX is unlikely to be optimal for the treatment of tuberculosis, but higher doses could be effective.

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Molecular characterisation of extensively drug-resistant Mycobacterium tuberculosis isolates in China

Cited by 13 publications

References 29 publications

<p>Prevalence, risk and genetic characteristics of drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China</p>

<p>Prevalence, risk and genetic characteristics of drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China</p>

Molecular characteristics of ofloxacin mono‐resistant Mycobacterium tuberculosis isolates from new and previously treated tuberculosis patients

Wild-Type and Non-Wild-Type Mycobacterium tuberculosis MIC Distributions for the Novel Fluoroquinolone Antofloxacin Compared with Those for Ofloxacin, Levofloxacin, and Moxifloxacin

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