Journal of Antimicrobial Chemotherapy, Vol 41, 77-83, Copyright © 1998 by The British Society for Antimicrobial Chemotherapy
K Sato, T Akaki and H Tomioka
The in-vitro activities of KRM-1648, a new benzoxazinorifamycin,
clarithromycin and levofloxacin against clinical isolates of Mycobacterium
avium complex (MAC) were measured using various methods of assay and
compared with their in-vivo therapeutic activities against MAC infection in
mice. The MICs varied according to drug in the order KRM-1648 <<
clarithromycin < levofloxacin. However, KRM-1648 and clarithromycin but
not levofloxacin had similar therapeutic outcomes in MAC-infected mice.
KRM-1648 and clarithromycin given at clinical dosages caused 1 to 2 log
unit reductions in bacterial loads in the lungs of host mice. The values of
Cmax (lung)/MBC were more closely related to the therapeutic efficacy of
these drugs in mice than were MICs and MBCs alone. Potent microbicidal
activity was observed with KRM- 1648 and clarithromycin but not with
levofloxacin against extracellularly growing MAC (EG-MAC) in a liquid
medium. These two agents caused more than 3 log unit killing of MAC during
a 5 day incubation, when added at concentrations equivalent to Cmax (lung).
The anti-EG-MAC bactericidal activity of these drugs was greater than their
efficacy in mice in vivo. KRM-1648 and clarithromycin but not levofloxacin
caused respectively 2 and 0.5 log unit killing of intracellularly growing
MAC (IG-MAC) in murine peritoneal macrophages. The profiles of bacterial
killing effects of these agents against IG- MAC accurately reflected their
therapeutic effects in mice, although the in-vivo activity of KRM-1648 was
still overestimated using even this parameter.
ORIGINAL ARTICLES
Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages
Department of Microbiology and Immunology, Shimane Medical University, Japan.
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