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.
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.
Sato
K
K
Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
Tomioka
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D017291:Clarithromycin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D006801:Humans; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000254:growth & development; D011650:Pulmonary Alveoli / Q000382:microbiology*; D012294:Rifamycins / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D012294:Rifamycins; C068980:KRM 1648; D017291:Clarithromycin