Acquisition of Rifampin Resistance in Pulmonary Tuberculosis

Antimicrob Agents Chemother. 2017 Mar 24;61(4):e02220-16. doi: 10.1128/AAC.02220-16. Print 2017 Apr.

Abstract

Mycobacterium tuberculosis strains with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare, and fixed drug combinations typically prevent augmentation of resistance to single drugs. Fourteen newly diagnosed tuberculosis patients were treated with RIF alone for 14 days, and bacterial loads, including mutation frequencies, were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be RIF resistant after 30 days of monotherapy. This indicates that temporal and spatial windows of RIF monotherapy due to uneven drug distribution within lung lesions could contribute to the acquisition of resistance to RIF.

Keywords: resistance; rifampin; treatment; tuberculosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / pharmacology*
  • Bacterial Load / drug effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Colony Count, Microbial
  • DNA-Directed RNA Polymerases / genetics
  • DNA-Directed RNA Polymerases / metabolism
  • Drug Resistance, Bacterial / genetics
  • Gene Expression
  • Humans
  • Models, Statistical*
  • Mutation Rate
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics
  • Mycobacterium tuberculosis / growth & development
  • Mycobacterium tuberculosis / metabolism
  • Rifampin / pharmacokinetics
  • Rifampin / pharmacology*
  • Tissue Distribution
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • rpoB protein, Mycobacterium tuberculosis
  • DNA-Directed RNA Polymerases
  • Rifampin