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Statins increase rifampin mycobactericidal effect.

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 XDR-TB, is pressing. Our group has recently described 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 efficacy of two statins on the intracellular viability of mycobacteria within the macrophage, and atorvastatin effect on BALB/c mice M. leprae infection. 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 atorvastatin efficacy in control 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 M. bovis, M. leprae and M. tuberculosis. It is likely that statins association with the actual multidrug therapy could effectively reduce mycobacteria viability and tissue lesion in Leprosy and Tuberculosis patients, although epidemiological studies are still needed for confirmation.

More information

Type
Journal Article
Author
Lobato LS
Rosa PS
Ferreira JS
Neumann AS
Silva MG
Nascimento DC
Soares CT
Pedrini SCB
Oliveira DLSá
Monteiro CP
Pereira GMB
Ribeiro-Alves M
Hacker MA
Moraes MO
Pessolani MCV
Duarte RS
Lara FA
Year of Publication
2014
Journal
Antimicrobial Agents and Chemotherapy
Language
eng
ISSN Number
1098-6596
DOI
10.1128/AAC.01826-13
Alternate Journal
Antimicrob. Agents Chemother.
Publication Language
eng