Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex within murine peritoneal macrophages, human macrophage-like cells and human alveolar epithelial cells

Abstract

Profiles of the in-vitro antimicrobial effects of KRM-1648 and clarithromycin against Mycobacterium avium-intracellulare complex (MAC) within murine peritoneal macrophages, the THP-1 human macrophage cell line and the A-549 type II alveolar epithelial cell line were determined. MAC organisms grew more rapidly in A-549 and THP-1 cells than in murine peritoneal macrophages. Peritoneal macrophages produced significant amounts of reactive nitrogen intermediates in response to MAC infection, but A-549 and THP-1 cells did not. KRM-1648 progressively killed M. intracellulare residing in macrophages, but did not completely eliminate M. intracellulare from A-549 and THP-1 cells. Moreover, in the case of M. intracellulare-infected A-549 and THP-1 cells, bacterial regrowth was observed during the middle to late phase of cultivation. Clarithromycin exhibited moderate levels of microbicidal activity against M. intracellulare residing in peritoneal macrophages, THP-1 cells and A-549 cells. The profiles of clarithromycin-mediated killing or inhibition of the intracellular organisms in A-549 and THP-1 cells were similar to those observed for organisms within peritoneal macrophages.