Drug resistance in mycobacterium tuberculosis: Molecular mechanisms challenging fluoroquinolones and pyrazinamide effectiveness

Research output: Contribution to journalArticle

Abstract

Physicians are more and more often challenged by difficult-to-treat cases of TB. They include patients infected by strains of Mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin (multidrug-resistant TB) or to at least one fluoroquinolone (FQ) and one injectable, second-line anti-TB drug in addition to isoniazid and rifampicin (extensively drugresistant TB). The drug treatment of these cases is very long, toxic, andexpensive, and, unfortunately, the proportion of unsatisfactory outcomes is still considerably high. Although FQs and pyrazinamide (PZA) are backbone drugs in the available anti-TB regimens, several uncertainties remain about their mechanisms of action andeven more remain about the mechanisms leading to drug resistance. From a clinical point of view, a better understanding of the genetic basis of drug resistance will aid (1) clinicians to provide quality clinical management to both drug-susceptible and drug-resistant TB cases (while preventingemergence of further resistance), and (2) developers of new molecular-based diagnostic assays to better direct their researcheff orts toward a new generation of sensitive, specific, cheap, andeasy-to-use pointof-care diagnostics. In this review we provide an update on the molecular mechanisms leading to FQ-and PZA-resistance in M tuberculosis.

Original languageEnglish
Pages (from-to)1135-1143
Number of pages9
JournalChest
Volume147
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

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Pyrazinamide
Fluoroquinolones
Mycobacterium tuberculosis
Drug Resistance
Pharmaceutical Preparations
Isoniazid
Rifampin
Molecular Pathology
Poisons
Uncertainty
Tuberculosis
Physicians
Injections

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

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title = "Drug resistance in mycobacterium tuberculosis: Molecular mechanisms challenging fluoroquinolones and pyrazinamide effectiveness",
abstract = "Physicians are more and more often challenged by difficult-to-treat cases of TB. They include patients infected by strains of Mycobacterium tuberculosis that are resistant to at least isoniazid and rifampicin (multidrug-resistant TB) or to at least one fluoroquinolone (FQ) and one injectable, second-line anti-TB drug in addition to isoniazid and rifampicin (extensively drugresistant TB). The drug treatment of these cases is very long, toxic, andexpensive, and, unfortunately, the proportion of unsatisfactory outcomes is still considerably high. Although FQs and pyrazinamide (PZA) are backbone drugs in the available anti-TB regimens, several uncertainties remain about their mechanisms of action andeven more remain about the mechanisms leading to drug resistance. From a clinical point of view, a better understanding of the genetic basis of drug resistance will aid (1) clinicians to provide quality clinical management to both drug-susceptible and drug-resistant TB cases (while preventingemergence of further resistance), and (2) developers of new molecular-based diagnostic assays to better direct their researcheff orts toward a new generation of sensitive, specific, cheap, andeasy-to-use pointof-care diagnostics. In this review we provide an update on the molecular mechanisms leading to FQ-and PZA-resistance in M tuberculosis.",
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