Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

Rendón, Adrián; Tiberi, Simon; Scardigli, Anna; D’Ambrosio, Lia; Centis, Rosella; Caminero, José A.; Migliori, Giovanni Battista

doi:10.21037/jtd.2016.10.14

Cited by 47 publications

(28 citation statements)

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“…Some of these unapproved MDR-TB treatment drugs include co-trimoxazole ISSN: 2520-3096 (including trimethoprim/sulfamethoxazole), bedaquiline (elevated dosage), linezolid (elevated dosage), and ciprofloxacin ( Van et al, 2013) [33] (ClinicalTrials.Gov, 2019) [4] (Shim & Jo, 2013) [29]. Furthermore, the clinicians and researchers must study new therapeutic combinations of the approved MDR-TB management drugs in the context of enhancing the therapeutic outcomes while concomitantly shortening the length of therapy and minimizing the intensity/frequency of side-effects (Rendon et al, 2016) [26]. However, the short-term MDR-TB treatment improvement measures are based on the development of the appropriate drug susceptibility interventions to effectively individualize the therapeutic approaches for reducing the overall treatment tenure.…”

Section: Conclusion and Future Recommendationsmentioning

confidence: 99%

Untitled

2019

TIJCR

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Section: Conclusion and Future Recommendationsmentioning

confidence: 99%

Untitled

2019

TIJCR

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“…Since the 1940s, several drugs have been developed for the treatment of TB (Sotgiu et al, 2015;Kurz et al, 2016). These drugs can be classified as first-line anti-TB drugs, including the isoniazid (INH), rifampicin, pyrazinamide, and ethambutol, as well as other second-line drugs, which are used in cases of treatment failure (Rendon et al, 2016). The first-line anti-TB drug, INH, which was initially shown to have anti-TB activity in 1952 (Fox, 1952), is suitable for treatment when M. tuberculosis is replicating (Chakraborty and Rhee, 2015).…”

Section: Introductionmentioning

confidence: 99%

Two Novel katG Mutations Conferring Isoniazid Resistance in Mycobacterium tuberculosis

et al. 2020

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Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is among the top 10 leading causes of death worldwide. The treatment course for TB is challenging; it requires antibiotic administration for at least 6 months, and bacterial drug resistance makes treatment even more difficult. Understanding the mechanisms of resistance is important for improving treatment. To investigate new mechanisms of isoniazid (INH) resistance, we obtained three INH-resistant (INH-R) M. tuberculosis clinical isolates collected by the Taiwan Centers for Disease Control (TCDC) and sequenced genes known to harbor INH resistance-conferring mutations. Then, the relationship between the mutations and INH resistance of these three INH-R isolates was investigated. Sequencing of the INH-R isolates identified three novel katG mutations resulting in R146P, W341R, and L398P KatG proteins, respectively. To investigate the correlation between the observed INH-R phenotypes of the clinical isolates and these katG mutations, wild-type katG from H37Rv was expressed on a plasmid (pMN437-katG) in the isolates, and their susceptibilities to INH were determined. The plasmid expressing H37Rv katG restored INH susceptibility in the two INH-R isolates encoding the W341R KatG and L398P KatG proteins. In contrast, no phenotypic change was observed in the KatG R146P isolate harboring pMN437-katG. H37Rv isogenic mutant with W341R KatG or L398P KatG was further generated. Both showed resistant to INH. In conclusion, W341R KatG and L398P KatG conferred resistance to INH in M. tuberculosis, whereas R146P KatG did not affect the INH susceptibility of M. tuberculosis.

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“…1 Multidrug-resistant tuberculosis (MDR-TB) is defined as that which is resistant to both rifampin and isoniazid, whereas extensively drug-resistant tuberculosis (XDR-TB) is defined as that which, in addition to being resistant to rifampin and isoniazid, is resistant to a fluoroquinolone and a second-line injectable drug; these are the most worrying forms of tuberculosis. 2 …”

Section: Introductionmentioning

confidence: 99%