Statins increase rifampin mycobactericidal effect

Antimicrob Agents Chemother. 2014 Oct;58(10):5766-74. doi: 10.1128/AAC.01826-13. Epub 2014 Jul 21.

Abstract

Mycobacterium leprae and Mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (XDR-TB), is pressing. Our group recently showed that M. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and Schwann cells, facilitating its viability and replication. Considering these previous results, we investigated the efficacies of two statins on the intracellular viability of mycobacteria within the macrophage, as well as the effect of atorvastatin on M. leprae infections in BALB/c mice. We observed that intracellular mycobacteria viability decreased markedly after incubation with both statins, but atorvastatin showed the best inhibitory effect when combined with rifampin. Using Shepard's model, we observed with atorvastatin an efficacy in controlling M. leprae and inflammatory infiltrate in the BALB/c footpad, in a serum cholesterol level-dependent way. We conclude that statins contribute to macrophage-bactericidal activity against Mycobacterium bovis, M. leprae, and M. tuberculosis. It is likely that the association of statins with the actual multidrug therapy effectively reduces mycobacterial viability and tissue lesion in leprosy and tuberculosis patients, although epidemiological studies are still needed for confirmation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / therapeutic use*
  • Atorvastatin
  • Cell Line
  • Drug Synergism
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Leprosy / drug therapy
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium leprae / drug effects*
  • Mycobacterium leprae / pathogenicity*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / pathogenicity
  • Pyrroles / therapeutic use
  • Rifampin / therapeutic use*
  • Simvastatin / therapeutic use

Substances

  • Antitubercular Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin
  • Simvastatin
  • Rifampin