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Acquisition of Rifampin Resistance in Pulmonary Tuberculosis

Xavier A Kayigire1,2, Sven O Friedrich3,2, Lize van der Merwe2

  • 1Division of Molecular Biology and Human Genetics, MRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.

Antimicrobial Agents and Chemotherapy
|February 8, 2017
PubMed

Insights

Spontaneous resistance to rifampin (RIF) in tuberculosis is rare. However, RIF monotherapy in patients may create conditions for RIF-resistant Mycobacterium tuberculosis to emerge, even with limited exposure.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Spontaneous mutations conferring rifampin resistance in Mycobacterium tuberculosis are rare.
  • Fixed drug combinations generally prevent the emergence of single-drug resistance.

Purpose of the Study:

  • To investigate the potential for rifampin monotherapy to select for resistant Mycobacterium tuberculosis strains.
  • To assess the frequency of rifampin resistance under specific monotherapy conditions.

Main Methods:

  • Fourteen newly diagnosed tuberculosis patients received rifampin monotherapy for 14 days.
  • Bacterial loads and mutation frequencies were determined.
  • A statistical model estimated resistance levels after 30 days.

Main Results:

  • A statistical model predicted that 1% of remaining viable mycobacteria could be rifampin-resistant after 30 days of monotherapy.
  • This suggests a potential window for resistance acquisition.

Conclusions:

  • Temporal and spatial variations in rifampin drug distribution within lung lesions during monotherapy could facilitate the emergence of rifampin resistance.
  • Even rare spontaneous mutations can be selected under specific therapeutic conditions.
Keywords:
resistancerifampintreatmenttuberculosis

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