Mycobacterium tuberculosis Is Selectively Killed by Rifampin and Rifapentine in Hypoxia at Neutral pH

Antimicrob Agents Chemother. 2017 Feb 23;61(3):e02296-16. doi: 10.1128/AAC.02296-16. Print 2017 Mar.

Abstract

The activities of rifampin, rifapentine, bedaquiline, PA-824, clofazimine, nitazoxanide, isoniazid, amikacin, moxifloxacin, niclosamide, thioridazine, and pyrazinamide were tested against nonreplicating (dormant) Mycobacterium tuberculosis H37Rv under conditions of hypoxia at pHs 5.8 and 7.3, mimicking environments of cellular granulomas and caseous granulomas, respectively. At pH 5.8, several drugs killed dormant bacilli, with the best being rifampin and rifapentine. At pH 7.3, only rifampin and rifapentine efficiently killed dormant bacilli, while all other drugs showed little activity.

Keywords: Mycobacterium tuberculosis; dormancy; hypoxia; killing; pH; rifampin; rifapentine; tuberculosis.

MeSH terms

  • Anaerobiosis
  • Antitubercular Agents / pharmacology*
  • Hydrogen-Ion Concentration
  • Isonicotinic Acids / pharmacology
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Nitroimidazoles / pharmacology
  • Phenazines / pharmacology
  • Quinolines / pharmacology
  • Rifampin / analogs & derivatives*
  • Rifampin / pharmacology*
  • Thiazoles / pharmacology

Substances

  • Antitubercular Agents
  • Isonicotinic Acids
  • Nitroimidazoles
  • Phenazines
  • Quinolines
  • Thiazoles
  • Rifampin
  • rifapentine