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Related Experiment Videos

Drug tolerance in Mycobacterium tuberculosis.

R S Wallis1, S Patil, S H Cheon

  • 1Case Western Reserve University, Cleveland Ohio, USA. rsw@po.cwru.edu

Antimicrobial Agents and Chemotherapy
|October 30, 1999
PubMed
Summary

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Mycobacterium tuberculosis drug tolerance, a delayed killing of bacteria in vitro, is linked to longer treatment persistence and relapse in tuberculosis patients. This phenotypic tolerance may not be drug-specific.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Tuberculosis treatment outcomes vary, with some patients rapidly clearing Mycobacterium tuberculosis while others experience prolonged persistence.
  • Understanding factors influencing treatment failure, such as mycobacterial drug tolerance, is crucial for improving tuberculosis therapy.

Purpose of the Study:

  • To investigate the relationship between mycobacterial drug tolerance, persistence of infection, and relapse in patients with pulmonary tuberculosis.
  • To determine if drug tolerance is associated with treatment outcomes in drug-susceptible tuberculosis.

Main Methods:

  • Analyzed 39 drug-susceptible Mycobacterium tuberculosis isolates from patients in Brazil and Uganda.
  • Assessed in vitro drug killing rates (bactericidal activity) and measured mycobacterial growth index (GI) in BACTEC 12B medium.

Related Experiment Videos

  • Correlated in vitro drug tolerance with clinical outcomes including treatment persistence and relapse.

    • Main Results:

    • Rifampin demonstrated the greatest bactericidal activity, followed by isoniazid-ethambutol, then ethambutol.
    • Isolates from patients who relapsed or had prolonged persistence showed significantly higher tolerance to isoniazid-ethambutol and rifampin.
    • Strain tolerance to isoniazid and rifampin predicted the duration of persistence during therapy.

    Conclusions:

    • Mycobacterial drug tolerance is a significant factor associated with poor treatment outcomes in tuberculosis.
    • Tolerance appears to be a phenotypic trait that may emerge during prolonged in vivo drug exposure.
    • Drug tolerance, rather than minimum inhibitory concentration (MIC), may be a key determinant in tuberculosis treatment success.