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Free Content Pyrazinamide is not active against Mycobacterium tuberculosis residing in cultured human monocyte-derived macrophages [Unresolved issues]

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Abstract:

SETTING: Mycobacteriology Laboratory, National Jewish Medical and Research Center, Denver, Colorado.

OBJECTIVE: To evaluate the antimicrobial activity of pyrazinamide against Mycobacterium tuberculosis in cultured human monocyte-derived normal and activated macrophages.

DESIGN: Monocytes separated from human blood were incubated in plastic plates for seven days to mature into macrophage monolayers. After activation with TNF-α or IFN-γ or without prior treatment, the macrophages were infected with M. tuberculosis. Various concentrations of pyrazinamide (PZA), morphazinamide (MZA) or isoniazid (INH) were added the next day, and the viable counts of the intracellular bacteria were determined at days 0, 4, and 8.

RESULTS: No inhibitory activity of PZA at any concentration was detected, while clear dose-dependent bacteriostatic and bactericidal activities were demonstrated by MZA and INH in the same experimental model.

CONCLUSIONS: PZA has neither bacteriostatic nor bactericidal activity against M. tuberculosis persisting or multiplying in cultured monocyte-derived human macrophages, and it might be that the well-known effectiveness of this drug in tuberculosis patients is not related to its supposed activity against intracellular bacterial subpopulations.

Keywords: macrophages; pyrazinamide; tuberculosis

Document Type: Miscellaneous

Affiliations: National Jewish Medical and Research Center, The University of Colorado Health Sciences Center, Denver, Colorado, USA

Publication date: June 1, 2000

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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