PA-824 , moxifloxacin and pyrazinamide combination therapy for tuberculosis

Expert Opin Investig Drugs. 2013 Jul;22(7):927-32. doi: 10.1517/13543784.2013.801958. Epub 2013 May 21.

Abstract

Introduction: New treatment regimens are urgently required for tuberculosis (TB). The existing four-drug regimen for TB is > 20 years old, with multidrug resistant (MDR) and extensively drug-resistant (XDR) TB on the increase.

Areas covered: Recently, the first novel potential combination TB treatment regimen for both drug-sensitive and MDR TB incorporating a new nitroimidazole compound, PA-824 , was investigated in a Phase II proof-of-concept clinical trial. This article reviews the rationale for this novel study, discusses the development strategy for PA-824 and highlights the study findings and its implications for future development of this regimen.

Expert opinion: Expert opinion will be offered on the utility of this new multicomponent treatment regimen. We will highlight how this study informs the development pathway for future novel TB regimens and explore the PA-824, moxifloxacin (MOX) and pyrazinamide combination as a first step towards developing a single treatment regimen for both drug-sensitive and drug-resistant diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / adverse effects
  • Antitubercular Agents / therapeutic use*
  • Aza Compounds / administration & dosage
  • Aza Compounds / adverse effects
  • Aza Compounds / therapeutic use*
  • Clinical Trials as Topic
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Fluoroquinolones
  • Humans
  • Molecular Structure
  • Moxifloxacin
  • Nitroimidazoles / administration & dosage
  • Nitroimidazoles / adverse effects
  • Nitroimidazoles / therapeutic use*
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / adverse effects
  • Pyrazinamide / therapeutic use*
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Aza Compounds
  • Drug Combinations
  • Fluoroquinolones
  • Nitroimidazoles
  • Quinolines
  • pretomanid
  • Pyrazinamide
  • Moxifloxacin