Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Int J Antimicrob Agents. 2012 May;39(5):376-80. doi: 10.1016/j.ijantimicag.2012.01.012. Epub 2012 Mar 23.

Abstract

Thioridazine (TDZ) in combination with antibiotics to which extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) is initially resistant yields a cure. This is due to the fact that TDZ enhances the killing of intracellular M. tuberculosis by non-killing macrophages, inhibits the genetic expression of efflux pumps of M. tuberculosis that extrude antibiotics prior to reaching their intended targets, and inhibits the activity of existing efflux pumps that contribute to the multidrug-resistant phenotype of M. tuberculosis. The combination of these effects of TDZ probably contributes to the successful recent cures of XDR-TB cases when the phenothiazine TDZ is used in combination with antibiotics to which the patient with XDR-TB was initially unresponsive.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antitubercular Agents / pharmacology*
  • Antitubercular Agents / therapeutic use
  • Biological Transport, Active / drug effects
  • Drug Resistance, Multiple, Bacterial*
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology
  • Extensively Drug-Resistant Tuberculosis / drug therapy
  • Extensively Drug-Resistant Tuberculosis / microbiology*
  • Humans
  • Macrophages / microbiology
  • Microbial Viability / drug effects
  • Mycobacterium tuberculosis / drug effects*
  • Thioridazine / pharmacology*
  • Thioridazine / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Enzyme Inhibitors
  • Thioridazine