Characterization of Polymorphisms Associated with Multidrug-Resistant Tuberculosis by Whole Genomic Sequencing: A Preliminary Report from Mexico

Zenteno-Cuevas, Roberto; Fernandez, Esdras; Viveros, Diana; Madrazo-Moya, Carlos Francisco; Cancino-Muñoz, Irving; Comas, Iñaki; González-Covarrubias, Vanessa; Barbosa-Amezcua, Martín; Cuevas-Córdoba, Betzaida

doi:10.1089/mdr.2019.0054

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…Interestingly, we identified one extensively drug-resistant strain. The presence of this type of strain has previously been reported in Mexico [30,36,37]. Extensively drug-resistant TB occurs as a consequence of the inadequate treatment of MDR-TB patients.…”

Section: Discussionmentioning

confidence: 78%

Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico

Valencia-Trujillo,

Avila-Trejo,

García-Reyes

et al. 2024

Pathogens

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Background: Drug-resistant tuberculosis (TB) is associated with higher mortality rates in patients with human immunodeficiency virus (HIV). In Mexico, the number of deaths due to TB among the HIV-positive population has tripled in recent years. Methods: Ninety-three Mycobacterium tuberculosis strains isolated from the same number of HIV-infected patients treated in a public hospital in Mexico City were studied to determine the drug resistance to first- and second-line anti-TB drugs and to identify the mutations associated with the resistance. Results: Of the 93 patients, 82.7% were new TB cases, 86% were male, and 73% had extrapulmonary TB. Most patients (94%) with a CD4 T-lymphocyte count <350 cells/mm3 were associated with extrapulmonary TB (p <0.0001), whilst most patients (78%) with a CD4 T-lymphocyte count >350 cells/mm3 were associated with pulmonary TB (p = 0.0011). Eighty-two strains were pan-susceptible, four mono-resistant, four poly-resistant, two multidrug-resistant, and one was extensively drug-resistant. In the rifampicin-resistant strains, rpoB S531L was the mutation most frequently identified, whereas the inhA C15T and katG S315T1 mutations were present in isoniazid-resistant strains. The extensively drug-resistant strain also contained the mutation gyrA D94A. Conclusions: These data highlight the need to promptly diagnose the drug resistance of M. tuberculosis among all HIV-infected patients by systematically offering access to first- and second-line drug susceptibility testing and to tailor the treatment regimen based on the resistance patterns to reduce the number of deaths in HIV-infected patients.

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Section: Discussionmentioning

confidence: 78%

Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico

Valencia-Trujillo,

Avila-Trejo,

García-Reyes

et al. 2024

Pathogens

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“…However, the exact molecular mechanism of action remains unclear ( Schubert et al, 2017 ). Studies on genetic polymorphisms related to EMB thus far have focused on polymorphisms that occur in the gene of Mtb bacteria ( Zenteno-Cuevas et al, 2019 ). Only a few studies have explored gene polymorphisms in humans that have an impact on the clinical response to EMB, including resistance and toxicity.…”

Section: Introductionmentioning

confidence: 99%

“…In human genetic polymorphism studies of anti-TB, the majority focus on RIF or INH. These studies discussed polymorphisms related to clinical response and toxicity ( Baskaran and Sabina, 2017 ; Bao et al, 2018 ; Richardson et al, 2018 ; Yang et al, 2019 ; Zenteno-Cuevas et al, 2019 ; Rivière et al, 2020 ). However, EMB has an important role in the treatment of tuberculosis, such as maintaining the effectiveness of therapeutic regimens ( Horsburgh et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic polymorphism related to ethambutol outcomes and susceptibility to toxicity

et al. 2023

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The World Health Organization (WHO) stated that ensuring access to effective and optimal treatment is a key component to eradicate tuberculosis (TB) through the End TB Strategy. Personalized medicine that depends on the genetic profile of an individual is one way to optimize treatment. It is necessary because of diverse drug responses related to the variation in human DNA, such as single-nucleotide polymorphisms (SNPs). Ethambutol (EMB) is a drug widely used as the treatment for Mycobacterium Tuberculosis (Mtb) and/non-tuberculous mycobacteria and has become a potential supplementary agent for a treatment regimen of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. In human genetic polymorphism studies of anti-tuberculosis, the majority focus on rifampicin or isoniazid, which discuss polymorphisms related to their toxicity. Whereas there are few studies on EMB, the incidence of EMB toxicity is lower than that of other first-line anti-TB drugs. To facilitate personalized medicine practice, this article summarizes the genetic polymorphisms associated with alterations in the pharmacokinetic profile, resistance incidence, and susceptibility to EMB toxicity. This study includes 131 total human studies from 17 articles, but only eight studies that held in the low-middle income country (LMIC), while the rest is research conducted in developed countries with high incomes. Personalized medicine practices are highly recommended to maintain and obtain the optimal therapeutic effect of EMB.

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Global status of phenotypic pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates: an updated systematic review and meta-analysis

Wang

Tang

Heidari

et al. 2023

Journal of Chemotherapy

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Characterization of Polymorphisms Associated with Multidrug-Resistant Tuberculosis by Whole Genomic Sequencing: A Preliminary Report from Mexico

Cited by 4 publications

References 30 publications

Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico

Phenotypic and Genotypic Drug Resistance of Mycobacterium tuberculosis Strains Isolated from HIV-Infected Patients from a Third-Level Public Hospital in Mexico

Genetic polymorphism related to ethambutol outcomes and susceptibility to toxicity

Global status of phenotypic pyrazinamide resistance in Mycobacterium tuberculosis clinical isolates: an updated systematic review and meta-analysis

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