The Path of Anti-Tuberculosis Drugs: From Blood to Lesions to Mycobacterial Cells

Nat Rev Microbiol. 2014 Mar;12(3):159-67. doi: 10.1038/nrmicro3200. Epub 2014 Feb 3.

Abstract

For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. However, most currently used anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution, and this has contributed to the long duration and limited success of current therapies. In this Progress article, I describe new methods to quantify and image drug distribution in infected lung tissue and in mycobacterial cells, and I explore how this technology could be used to design optimized multidrug regimens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / blood
  • Antitubercular Agents / pharmacokinetics*
  • Antitubercular Agents / therapeutic use
  • Drug Delivery Systems*
  • Drug Resistance, Bacterial
  • Humans
  • Lung / metabolism*
  • Lung / microbiology
  • Lung / pathology
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / metabolism
  • Tissue Distribution
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents