Whole-Genome Sequencing for Resistance Level Prediction in Multidrug-Resistant Tuberculosis

Li, Jinli; Yang, Tingting; Chuangyue, Hong; Zheng, Yan-Peng; Wu, Likai; Gao, Qian; Yang, Hui; Tan, Wenfa

doi:10.1128/spectrum.02714-21

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Mutations in the inhA and ahpC promoters usually result in low-level resistance. But it would become a high-level resistance when they appeared with katG mutation ( 34 ). Moreover, of the 64 drug-resistant MTB-positive individuals we identified, 10 of them were resistant to two of the first-line therapy antibiotics, and eight were resistant to three.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy

Chen,

Sechi,

Molicotti

2024

Microbiol Spectr

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Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) are the most common pathogens of mycobacterial infection, and their prevalence varies around the world. This study aimed to estimate the prevalence of mycobacterial infection and drug resistance in North Sardinia, Italy and to optimize the process of mycobacteria identification. From January 2020 to April 2023, samples from 1,836 suspected individuals in North Sardinia were analyzed. Conventional methods (microscopy smear and culture) and molecular methods (polymerase chain reaction, DNA probe, and mass spectrum) were used in MTB and NTM identification. Among 1,836 suspected individuals, 89 were MTB-positive and 44 were NTM-positive. Bronchial aspiration and bronchoalveolar lavage performed well as substitute specimens for sputum in MTB detection. For drug resistance, 71.91% of MTB and 83.33% of NTM were resistant to at least one antibiotic. The average turn-around time of MTB, slowly growing mycobacteria, and rapidly growing mycobacteria was 7.12, 48.87, and 11.27 days, respectively. Overall, our results show that the prevalence of mycobacterial infection in North Sardinia is relatively optimistic. However, the high proportion of drug resistance detected in the isolates is alarming. The implementation of advanced techniques could help optimize the process of mycobacteria identification. IMPORTANCE Mycobacterial infection is a major threat to public health worldwide. Accurate identification of infected species and drug resistance detection are critical factors in treatment. We focused on shortening the turn-around time of identifying mycobacteria species and antibiotic resistance tests.

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Section: Discussionmentioning

confidence: 99%

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy

Chen,

Sechi,

Molicotti

2024

Microbiol Spectr

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“…Microdilution plates have sought to address inconsistencies between phenotypic DST methods by assessing minimum inhibitory concentrations (MICs) rather than critical concentrations for ethambutol(41). Studies employing the Sensititre™ Mycobacterium tuberculosis MYCOTBI AST plate also report emb B406 mutations among strains exhibiting resistance below the 5 μg/mL breakpoint for ethambutol(43–45). Liu et al .…”

Section: Discussionmentioning

confidence: 99%

“…These observations are accompanied by a recommendation that the BACTEC™ MGIT™ 960 critical concentration be lowered to ensure resistance at or near the 5 µg/mL critical concentration is detected(15).Microdilution plates have sought to address inconsistencies between phenotypic DST methods by assessing minimum inhibitory concentrations (MICs) rather than critical concentrations for ethambutol(41). Studies employing the Sensititre™ Mycobacterium tuberculosis MYCOTBI AST plate also report embB406 mutations among strains exhibiting resistance below the 5 µg/mL breakpoint for ethambutol(43)(44)(45). Liu et al (2021) explain that embB406 mutations elevated ethambutol MICs at sub-threshold levels (44).…”

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confidence: 99%

Mutations inembB406 are associated with low-level ethambutol resistance in CanadianMycobacterium tuberculosisisolates

Hiebert

Sharma

Rabb

et al. 2023

Preprint

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Background: InMycobacterium tuberculosis, molecular predictions of ethambutol resistance rely primarily on the detection of mutations withinembB. However, discordance betweenembB406 mutations and phenotypic drug sensitivity questions its clinical significance. This study aims to decipher the association ofembB406 mutations with ethambutol resistance inM. tuberculosis. Methods: AllM. tuberculosisisolates from our culture collection containingembB406 mutations (n=16) and pan-sensitive control isolates (n=10) were selected for this study. Phenotypic drug susceptibility testing for ethambutol was performed in duplicate on the BACTEC™ MGIT™ 960 at concentrations of 2, 3, 4, and 5 μg/mL with strain H37Rv as assay control. Whole genome sequencing was performed on Illumina Miseq for drug resistance predictions (MyKrobe Predictor v.0.7.0), phylogenomics (SNVPhyl v.1.2.3) and single nucleotide polymorphism analysis (Snippy). Results: TwoembB406 mutation subtypes were found among 16 strains: Gly406Asp and Gly406Ala. MyKrobe predicted all strains of either subtype to be ethambutol resistant. However, 12 of 16 strains appear phenotypically sensitive at 5 µg/mL but exhibit variable resistance between 2-4 µg/mL. Of these 12 strains, a newly described frameshift mutation in regulator embR (Gln258fs) was found in 9 strains. Conclusions: Mutations inembB406 are associated with low-level ethambutol resistance currently undetectable by the critical concentration of 5 μg/mL for ethambutol. Novel mutations are predicted to exacerbate variability in ethambutol resistance. We suggest amendment to molecular and phenotypic drug susceptibility testing to improve ethambutol DST sensitivity and specificity as well as concordance between rapid and gold standard methods.

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“…Resistance to isoniazid (H) and rifampicin (R) -the two most powerful OAT regimens -known as Multidrug-Resistant Tuberculosis (MDR-TB) has become a major concern in controlling TB cases. Patients with MDR-TB cannot be cured with first-line OAT regimens (Jiang et al, 2023;Mbona et al, 2023;Santos et al, 2022) Worse treatment outcomes, high mortality rates, longer duration of treatment (approximately two years), high costs, and various other complications make the treatment of MDR-TB more complex compared to drug-sensitive TB (Li et al, 2022;Trubnikov et al, 2021;Usmanova et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Multidrug Resistant Tuberculosis (MDR-TB) Factors: Literature Review

Subairi,

Muhith,

Zahro

2023

janh

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Background: Multidrug-resistant tuberculosis (MDRTB) is the biggest problem in preventing and eradicating TB in the world. MDR-TB occurs if the tuberculosis germs are resistant to various first-line OAT, at least two drugs, namely isoniazid and rifampicin. The emergence of MDR-TB cases presents new obstacles and challenges to the effectiveness of TB control programs due to difficult diagnosis, high rates of therapy failure, and death. This literature review aims to determine the factors that cause multidrug-resistant tuberculosis (MDR-TB). Methods: The method used in this article is a literature review using journal databases from Pubmed and Google Scholar in the 2020-2023 time period with the keywords "drug MDR TB," "multi-drug TB MDR factors," "TB MDR," and " resistant TB medicine" found in 1,990 articles, 304 from Pubmed, and 1,960 from Google Scholar). Articles were selected according to the criteria, and the result was 20 articles ready to be reviewed Results: The results of this study show that risk factors have been proven to show that there is a significant relationship between history of diabetes mellitus, history of TB treatment, patient motivation, adherence to taking medication, duration of TB treatment, status of drug side effects, employment, marital status, economic level, history of contact with patients. MDR TB, stress level, and family support are related to the incidence of MDR TB Conclusion: The conclusion of the 20 articles reviewed shows that age, gender, compliance with taking medication, diabetes mellitus, and a history of contact with MDR TB patients are the factors that most influence the occurrence of MDR TB

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Whole-Genome Sequencing for Resistance Level Prediction in Multidrug-Resistant Tuberculosis

Abstract: Whole-genome sequencing (WGS) has excellent potential in drug-resistance prediction. The MICs are essential indications of adding a particular antituberculosis drug dosage or changing the entire treatment regimen.

Cited by 8 publications

References 21 publications

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy

Evaluation of mycobacteria infection prevalence and optimization of the identification process in North Sardinia, Italy

Mutations inembB406 are associated with low-level ethambutol resistance in CanadianMycobacterium tuberculosisisolates

Multidrug Resistant Tuberculosis (MDR-TB) Factors: Literature Review

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