Assessment of the GenoType MTBDRsl VER 2.0 compared to the phenotypic drug susceptibility testing and whole genome sequencing for the rapid detection of resistance to fluoroquinolone and second-line injectable drugs among rifampicin-resistant Mycobacterium tuberculosis isolates

Kardan-Yamchi, Jalil; Amini, Sirus; Hamzelou, Gholamreza; Foroushani, Abbas Rahimi; Ghodousi, Arash; Cirillo, Daniela María; Feizabadi, Mohammad M.

doi:10.1007/s00203-021-02387-3

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…The key, therefore, is to identify single nucleotide polymorphisms (SNPs) that are responsible for or strongly associated with resistance. In the case of the first-line drug in Mtb treatment, mutations in the 81-bp rifampicin resistance determining region (RRDR) of the rpoB gene, also known as a hotspot region, have been accurate predictors of rifampicin resistance in many studies [69][70][71]. On the other hand, it has been established that INH resistance, predominantly mediated through loss of catalase-peroxidase activity via mutations in katG, produces high-level resistant strains [18,72,73].…”

Section: Discussionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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Background Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. Results Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. Conclusion This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

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Section: Discussionmentioning

confidence: 99%

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

et al. 2022

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“…The resistance to rifampicin generally is exhibited by mutations in the 81-bp rifampicin resistance-determining region (RRDR) of the rpoB gene, also known as hotspot region, have been accurate predictors of rifampicin resistance in many studies (45,54,55). In fact, 60.9% of the RIF-resistant isolates possessed the S450L mutation in rpoB, in agreement with previous studies that reported a higher prevalence of this mutation associated with high levels of resistance, as well as H445Y and H445D (68,69).…”

Section: Discussionmentioning

confidence: 99%

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Morey-León

Mejía-Ponce

Pardo

et al. 2023

Preprint

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Tuberculosis (TB) is among the most deadly diseases that affect worldwide, its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, non-adherence to treatment and circulation of previously resistant isolates ofMycobacterium tuberculosis. The aim in this study was evaluate the performance and functionalities of web-based tools: Mykrobe, TB-profiler, PhyReSse, KvarQ, and SAM-TB for detecting resistance in isolate ofMycobacterium tuberculosisin comparison with conventional drug susceptibility tests. We used 88M. tuberculosisisolates which were drug susceptibility tested and subsequently fully sequenced and web-based tools analysed. Statistical analysis was performed to determine the correlation between genomic and phenotypic analysis. Our data show that the main sub-lineage was LAM (44.3%) followed by X-type (23.0%) within isolates evaluated. Mykrobe has a higher correlation with DST (98% of agreement and 0.941Cohen's Kappa) for global resistance detection, but SAM-TB, PhyReSse and Mykrobe had a better correlation with DST for first-line drug analysis individually. We have identified that 50% of mutations characterised by all web-based tools were canonical inrpoB, katG,embB, pncA, gyrAandrrsregions. Our findings suggest that SAM-TB, PhyReSse and Mykrobe were the web-based tools more efficient to determine canonical resistance-related mutations, however more analysis should be performed to improve second-line detection. The improvement of surveillance programs for the TB isolates applying WGS tools against first line drugs, MDR-TB and XDR-TB are priorities to discern the molecular epidemiology of this disease in the country.

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“…Following the list of WHO regions, 63 20 reference centres enrolled patients from the European region, 25,28,41,42,44,[47][48][49]52,54,55,57,59,62 10 from the Western Pacific Region, 28,32,34,36,38,45,46,51,60,61 8 from the African Region, 25,30,39,40,43,48,56,58 6 from the South-East Asian Region, 25,29,31,33,35,48,53 3 from the Eastern Mediterranean Region, 26,27,37 3 from the Region of the Americas. 28,50 Among the included studies, two (5.3%), 25,28 10 (26.3%), 26,29,34,35,39,…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The overall pooled prevalence of XDR-TB pattern estimated by the DST was assessed in 28 (73.7%) studies 26,27,29,56,58,59,61 and was 15% (95% CI = 11-20; I 2 = 95.6%). The pooled prevalence of resistance was higher for fluoroquinolones (FQ) (34%; 95% CI = 27-41; I 2 = 97.6%), followed by kanamycin (KAN) (28%; 95% CI = 21-36; I 2 = 97%), amikacin (AMK) (18%; 95% CI = 14-23; I 2 = 93.6%), and capreomycin (CM) (17%; 95% CI = 13-21; I 2 = 92%) (Fig.…”

Section: Resistance Patternsmentioning

confidence: 99%

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Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

Saderi¹,

Puci²,

Lorenzo³

et al. 2022

Archivos de Bronconeumología

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Assessment of the GenoType MTBDRsl VER 2.0 compared to the phenotypic drug susceptibility testing and whole genome sequencing for the rapid detection of resistance to fluoroquinolone and second-line injectable drugs among rifampicin-resistant Mycobacterium tuberculosis isolates

Cited by 8 publications

References 19 publications

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

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