scholarly journals Early Detection of Emergent Extensively Drug-Resistant Tuberculosis by Flow Cytometry-Based Phenotyping and Whole-Genome Sequencing

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Max R. O’Donnell ◽  
Michelle H. Larsen ◽  
Tyler S. Brown ◽  
Paras Jain ◽  
Vanisha Munsamy ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Genome Sequencing ◽  
Low Frequency ◽  
Whole Genome ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTA critical gap in tuberculosis (TB) treatment is detection of emergent drug resistance. We hypothesized that advanced phenotyping with whole-genome sequencing (WGS) will detect low-frequencyMycobacterium tuberculosisdrug resistance. We assessed a reporter mycobacteriophage (Φ2GFP10)in vitroto detect drug-resistant subpopulations and predictM. tuberculosisbactericidal activity in this pilot study. Subsequently, we prospectively studied 20 TB patients with serial Φ2GFP10, Xpert MTB/RIF, andM. tuberculosisculture through end of treatment. WGS was performed, and single nucleotide polymorphisms (SNPs) were examined to detect mixed infection in selectedM. tuberculosisisolates. ResistantM. tuberculosisisolates were detected at 1:100,000, and changes in cytometry-gated events were predictive ofin vitroM. tuberculosisbactericidal activity using the Φ2GFP10 assay. Emergent drug resistance was detected in one patient by Φ2GFP10 at 3 weeks but not by conventional testing (M. tuberculosisculture and GeneXpert). WGS revealed a phylogeographically distinct extensively drug-resistant tuberculosis (XDR-TB) genome, identical to an XDR-TB isolate from the patient’s spouse. Variant lineage-specific SNPs were present early, suggesting mixed infection as the etiology of emergent resistance with temporal trends providing evidence for selection during treatment. Φ2GFP10 can detect low-frequency drug-resistantM. tuberculosisand with WGS characterize emergentM. tuberculosisresistance. In areas of high TB transmission and drug resistance, rapid screening for heteroresistance should be considered.

scholarly journals THE CASE OF PRE-EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS DETECTION BY USING THE WHOLE GENOME SEQUENCING M.TUBERCULOSIS

CHEST Journal ◽  
2020 ◽  
Vol 157 (6) ◽  
pp. A18
Author(s):  
U. Kozhamkulov ◽  
A. Akhmetova ◽  
S. Rakhimova ◽  
A. Akilzhanova ◽  
A. Daniyarov ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

scholarly journals Antitubercular Activity of Disulfiram, an Antialcoholism Drug, against Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates

2012 ◽  
Vol 56 (8) ◽  
pp. 4140-4145 ◽  
Author(s):  
Yasuhiro Horita ◽  
Takemasa Takii ◽  
Tetsuya Yagi ◽  
Kenji Ogawa ◽  
Nagatoshi Fujiwara ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antitubercular Activity ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTThe antimycobacterial activities of disulfiram (DSF) and diethyldithiocarbamate (DDC) against multidrug- and extensively drug-resistant tuberculosis (MDR/XDR-TB) clinical isolates were evaluatedin vitro. Both DSF and DDC exhibited potent antitubercular activities against 42 clinical isolates ofM. tuberculosis, including MDR/XDR-TB strains. Moreover, DSF showed remarkable bactericidal activityex vivoandin vivo. Therefore, DSF might be a drug repurposed for the treatment of MDR/XDR-TB.

scholarly journals Whole-Genome Sequencing of a Haarlem Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolate from Medellín, Colombia

2016 ◽  
Vol 4 (3) ◽  
Author(s):  
N. Alvarez ◽  
D. Haft ◽  
U. A. Hurtado ◽  
J. Robledo ◽  
F. Rouzaud
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolate ◽  
Genome Sequencing ◽  
Draft Genome ◽  
Whole Genome ◽  
Drug Resistant ◽  
High Quality ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

Colombia is one of the 105 countries that has reported at least one case of extensively drug-resistant tuberculosis (XDR-TB). The Mycobacterium tuberculosis Haarlem genotype is ubiquitous worldwide. Here, we report the high-quality draft genome sequence of a Colombian Haarlem XDR-TB clinical isolate composed of 4,329,127 bp with 4,386 genes.

scholarly journals In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Yu Pang ◽  
Zhaojing Zong ◽  
Fengmin Huo ◽  
Wei Jing ◽  
Yifeng Ma ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Genetic Characteristics ◽  
Acquired Drug Resistance ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACT Extensively drug-resistant tuberculosis (XDR-TB) is a deadly form of TB that can be incurable due to its extreme drug resistance. In this study, we aimed to explore the in vitro susceptibility to bedaquiline (BDQ), delamanid (DMD), linezolid (LZD), clofazimine (CLO), moxifloxacin (MFX), and gatifloxacin (GAT) of 90 XDR-TB strains isolated from patients in China. We also describe the genetic characteristics of XDR-TB isolates with acquired drug resistance. Resistance to MFX, GAT, LZD, CLO, DMD, and BDQ was found in 82 (91.1%), 76 (84.4%), 5 (5.6%), 5 (5.6%), 4 (4.4%), and 3 (3.3%) isolates among the XDR-TB strains, respectively. The most frequent mutations conferring fluoroquinolone resistance occurred in codon 94 of the gyrA gene (57.8%), and the strains with these mutations (69.2%) were associated with high-level MFX resistance compared to strains with mutations in codon 90 (25.0%) (P < 0.01). All 5 CLO-resistant isolates exhibited ≥4-fold upward shifts in the BDQ MIC, which were attributed to mutations of codons 53 (60.0%) and 157 (20.0%) in the Rv0678 gene. Additionally, mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance. In conclusion, our data demonstrate that the XDR-TB strains exhibit a strikingly high proportion of resistance to the current anti-TB drugs, whereas BDQ, DMD, LZD, and CLO exhibit excellent in vitro activity against XDR-TB in the National Clinical Center on TB of China. The extensive cross-resistance between OFX and later-generation fluoroquinolones indicates that MFX and GAT may have difficulty in producing the desired effect for XDR-TB patients.

scholarly journals Whole-Genome Sequencing of Two Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from India

2019 ◽  
Vol 8 (7) ◽  
Author(s):  
Syed Beenish Rufai ◽  
Sarman Singh
Keyword(s):  
Public Health ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Health Concern ◽  
Whole Genome ◽  
Drug Resistant ◽  
Public Health Concern ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

The emergence of extensively drug-resistant tuberculosis (XDR-TB) presents a considerable challenge and a public health concern due to the high mortality rate of this disease. Whole-genome sequencing (WGS) of XDR-TB isolates is thus essential for understanding the mechanism of drug resistance.

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