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One concern in developing treatment regimens for tuberculosis (TB) is the need to target microorganisms in various growth states and microenvironments. Noting recent work showing that metronidazole was active against Mycobacterium tuberculosis in vitro under hypoxic conditions and additional findings that caseous granulomas are relatively hypoxic, a multinational team of investigators sought to determine whether metronidazole might be effective for treating TB.
The researchers used a cynomolgus macaque model in which animals with latent TB received no treatment, isoniazid (INH) alone for 6 months, or either metronidazole alone or INH plus rifampin for 2 months. The macaques then received 5 weeks of anti–tumor necrosis factor therapy to induc…