In this study, we determined the
MICs
and MBCs of levofloxacin (LVFX), clarithromycin (CAM), and KRM-1648 (KRM) for Mycobacterium tuberculosis (MTB) strain Kurono and M. avium complex (MAC) strain N-444 residing in MONO-MAC-6 human macrophage-like cells (MM6-Mφs) and A-549 human type II alveolar epithelial cells (A-549 cells). First, the
MICs
of LVFX for MTB replicating in MM6-Mφs (1μ/m
l) and A-549 cells (2 μg/m
l) were 4 to 8 times higher than its
MICs
for extracellular MTB growing in 7HSF medium. In contrast, the
MICs
of CAM for intracellular MTB residing in both the cells (2-4μg/m
l) were 4 to 8 times less than its
MICs
for extracellular MTB organisms. On the other hand, the
MICs
of KRM for extracellular MTB were nearly the same as its
MICs
for intracellular MTB residing in both types of the cells. Secondly, the
MICs
of LVFX and CAM for extracellular MAC were not significantly different from their
MICs
for intracellular MAC residing in MM6-Mφs and A-549 cells. The MIC of KRM for MAC residing in A-549 cells was 0.25μg/m
l, and this value was 32 times higher than its MIC for MAC residing in MM6-Mφs (0.008μg/m
l). Thirdly, the MBCs of test drugs for intracellular MTB and MAC residing in both types of the cells were somewhat longer than their MBCs for extracellular organisms. These findings indicate that, in the case of pulmonary infections with MTB or MAC, the therapeutic efficacy of a given drug, especially KRM, is more or less influenced by the bacterial location in the host lung tissues where the mycobacterial pathogens survive and multiply, i. e., either alveolar Mφs, type II alveolar epithelial cells, or surrounding environment.
抄録全体を表示