title: Studies on therapeutic activity of benzoxazinorifamycin KRM-1648 in combination with other antimicrobial agents and biological response modifiers interferon-gamma and granulocyte-macrophage colony-stimulating factor against M. leprae infection in athymic nude mice.
abstract: In the present study, we evaluated the in vivo anti-Mycobacterium leprae activities of KRM-1648 (KRM) given at long intervals in combination with ofloxacin (OFLX), clofazimine (CFZ), and dapsone (DDS). We also examined the combined effects of two biological response modifiers (BRMs), gamma interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the therapeutic efficacy of KRM. KRM exhibited potent therapeutic efficacy against M. leprae infection in mice even when given at 4-week intervals. KRM displayed increased efficacy in combination with OFLX, CFZ, and DDS (given three or six times per week) when given to mice in the multidrug combination KRM + OFLX + CFZ + DDS. The therapeutic efficacy of KRM given at 4-week intervals was increased by combined use with IFN-gamma but not by GM-CSF. Adoptive transfer of M. leprae antigen-primed lymphocytes of euthymic mice to recipient athymic nude mice with progressive M. leprae infection markedly enhanced host resistance.
authors.affiliation: Department of Microbiology and Immunology, Shimane Medical University, Izumo, Japan.
authors.forename: W W
authors.initials: WW
authors.lastname: Maw
authors.forename: H
authors.initials: H
authors.lastname: Tomioka
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002991:Clofazimine / Q000627:therapeutic use; D003622:Dapsone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D007917:Leprostatic Agents / Q000627:therapeutic use*; D007918:Leprosy / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015242:Ofloxacin / Q000627:therapeutic use; D012294:Rifamycins / Q000627:therapeutic use*
chemical_list: D007155:Immunologic Factors; D007917:Leprostatic Agents; D012294:Rifamycins; C068980:KRM 1648; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003622:Dapsone; D015242:Ofloxacin; D002991:Clofazimine