BIOMAT Database Logo BIOMAT Database Logo

Activities of the benzoxazinorifamycin KRM 1648 and ethambutol against Mycobacterium avium complex in vitro and in macrophages. 1994

C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California 90027.

KRM 1648 is a 4-aminobenzoxazine derivative of rifamycin S with potent in vitro activity against the Mycobacterium avium complex (MAC); the MIC for 90% of 24 MAC isolates from AIDS patients was 0.25 microgram/ml as determined by a radiometric broth macrodilution assay. KRM 1648 was bactericidal for MAC isolates in Middlebrook 7H9 broth, with a reduction in viability of 1 to 4 orders of magnitude over 72 h. In human macrophages, KRM 1648 also was bactericidal, with a reduction of 3 to 4 orders of magnitude in CFU per ml of macrophage lysate at a concentration of 1 microgram/ml; however, the bactericidal activity varied approximately 10-fold among the three MAC serovars tested. In growth medium, ethambutol potentiated the effect of KRM 1648, but this potentiation was modest when tested against MAC in macrophages and also varied between MAC strains. KRM 1648 has potential as an antimycobacterial agent for MAC disease, perhaps in combination with other agents so that the use of lower dosages of KRM 1648 than are needed with other rifamycins may be possible.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004977 Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. (From Smith and Reynard, Textbook of Pharmacology, 1992, p863) Dexambutol,EMB-Fatol,EMB-Hefa,Etambutol Llorente,Ethambutol Hydrochloride,Etibi,Miambutol,Myambutol,EMB Fatol,EMB Hefa,Hydrochloride, Ethambutol,Llorente, Etambutol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000904 Antibiotics, Antitubercular Substances obtained from various species of microorganisms that are, alone or in combination with other agents, of use in treating various forms of tuberculosis; most of these agents are merely bacteriostatic, induce resistance in the organisms, and may be toxic. Antitubercular Antibiotics
D012294 Rifamycins A group of ANTI-BACTERIAL AGENTS characterized by a chromophoric naphthohydroquinone group spanned by an aliphatic bridge not previously found in other known ANTI-BACTERIAL AGENTS. They have been isolated from fermentation broths of Streptomyces mediterranei. Rifamycin,Rifomycin,Rifomycins
D015269 Mycobacterium avium Complex A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS; M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs. Battey Bacillus,MAIC,Mycobacterium avium-intracellulare,Mycobacterium avium-intracellulare Complex,Mycobacterium intracellulare,Nocardia intracellularis
D017291 Clarithromycin A semisynthetic macrolide antibiotic derived from ERYTHROMYCIN that is active against a variety of microorganisms. It can inhibit PROTEIN SYNTHESIS in BACTERIA by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. 6-O-Methylerythromycin,A-56268,Biaxin,TE-031,A 56268,A56268,TE 031,TE031

Related Publications

C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
[In vitro activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis].
August 1996, Kekkaku : [Tuberculosis],
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.
June 1996, Antimicrobial agents and chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages.
January 1998, The Journal of antimicrobial chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.
January 1993, Antimicrobial agents and chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.
October 1995, Antimicrobial agents and chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
[In vivo activities of benzoxazinorifamycin KRM-1648, clarithromycin, and levofloxacin, or combination of KRM-1648 with diclofenac sodium against Mycobacterium avium infection induced in mice].
August 1997, Kekkaku : [Tuberculosis],
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.
February 1992, Antimicrobial agents and chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
In vitro and in vivo activities of KRM-1648, a newly synthesized benzoxazinorifamycin, against Mycobacterium marinum.
July 1992, Zentralblatt fur Bakteriologie : international journal of medical microbiology,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.
April 1993, Antimicrobial agents and chemotherapy,
C B Inderlied, and L Barbara-Burnham, and M Wu, and L S Young, and L E Bermudez
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.
March 1999, The Journal of antimicrobial chemotherapy,
Copied contents to your clipboard!