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The therapeutic efficacy of the benzoxazinorifamycin KRM-1648 was studied in an experimental rabbit infection system with avian Mycobacterium avium. The infected rabbits died from Yersin type infections, a peculiar type of experimental bovine tuberculosis characterized by a very rapid course, enlargement of the spleen and liver, and septic infection, 14 to 20 days after bacterial challenge, as evidenced by bacteremia and severe bacterial loads in the visceral organs. Histopathologic studies of the visceral organs of the infected rabbits revealed the development of numerous typical granulomatous lesions. This experimental rabbit infection system, features of which resemble certain features of disseminated M. avium complex infections in AIDS patients, was used to evaluate the therapeutic efficacy of KRM-1648, a newly synthesized benzoxazinorifamycin. KRM-1648 given orally at 25 and 50 mg/kg of body weight reduced the incidence and degree of bacteremia in infected rabbits and protected against subsequent death. Moreover, the drug allowed almost complete recovery of infected rabbits by week 7. KRM-1648 cleared infections in the lungs, liver, spleen, and kidneys and restored histopathologic features of healthy tissue in the visceral organs. KRM-1648 exhibited a more potent therapeutic effect against M. avium infection than rifampin and clarithromycin.

Titel:	Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.
Autor/in / Beteiligte Person:	Emori, M ; Saito, H ; Sato, K ; Tomioka, H ; Setogawa, T ; Hidaka, T
Link:	Full Text Finder (Volltext)
Zeitschrift:	Antimicrobial agents and chemotherapy, Jg. 37 (1993-04-01), Heft 4, S. 722-8
Veröffentlichung:	Washington, American Society for Microbiology, 1993
Medientyp:	academicJournal
ISSN:	0066-4804 (print)
DOI:	10.1128/AAC.37.4.722
Schlagwort:	Animals Bilirubin blood Body Weight physiology Eosine Yellowish-(YS) Hematoxylin Liver microbiology Liver pathology Lung microbiology Lung pathology Male Rabbits Spleen microbiology Spleen pathology Staining and Labeling Tuberculosis, Avian microbiology Tuberculosis, Avian pathology Antibiotics, Antitubercular therapeutic use Mycobacterium avium Rifamycins therapeutic use Tuberculosis, Avian drug therapy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Antimicrob Agents Chemother] 1993 Apr; Vol. 37 (4), pp. 722-8. MeSH Terms: Mycobacterium avium* ; Antibiotics, Antitubercular / therapeutic use ; Rifamycins / therapeutic use ; Tuberculosis, Avian / *drug therapy ; Animals ; Bilirubin / blood ; Body Weight / physiology ; Eosine Yellowish-(YS) ; Hematoxylin ; Liver / microbiology ; Liver / pathology ; Lung / microbiology ; Lung / pathology ; Male ; Rabbits ; Spleen / microbiology ; Spleen / pathology ; Staining and Labeling ; Tuberculosis, Avian / microbiology ; Tuberculosis, Avian / pathology References: Immunology. 1989 Jan;66(1):131-7. (PMID: 15493275) ; Antimicrob Agents Chemother. 1989 Sep;33(9):1531-4. (PMID: 2530933) ; Kekkaku. 1967 Dec;42(12):511-6. (PMID: 5598300) ; Antimicrob Agents Chemother. 1977 May;11(5):773-9. (PMID: 879732) ; Nature. 1979 Mar 29;278(5703):451-3. (PMID: 313007) ; Antimicrob Agents Chemother. 1981 Nov;20(5):666-77. (PMID: 6798925) ; Am Rev Respir Dis. 1982 Jan;125(1):43-8. (PMID: 7065508) ; Rev Infect Dis. 1986 Nov-Dec;8(6):1024-33. (PMID: 3541122) ; Am Rev Respir Dis. 1988 Mar;137(3):711-5. (PMID: 2830814) ; Zentralbl Bakteriol Mikrobiol Hyg A. 1989 Jan;270(3):345-60. (PMID: 2929188) ; J Infect Dis. 1989 Dec;160(6):1037-41. (PMID: 2584751) ; Res Microbiol. 1990 Feb;141(2):191-270. (PMID: 2345798) ; Res Microbiol. 1990 Feb;141(2):206-12. (PMID: 2345799) ; Ann Intern Med. 1990 Sep 1;113(5):358-61. (PMID: 2382918) ; Diagn Microbiol Infect Dis. 1990 Sep-Oct;13(5):429-33. (PMID: 2282778) ; Antimicrob Agents Chemother. 1991 Mar;35(3):542-7. (PMID: 2039206) ; Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):564-9. (PMID: 1832527) ; Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):856-8. (PMID: 1532486) ; Antimicrob Agents Chemother. 1992 Feb;36(2):387-93. (PMID: 1605603) ; Tubercle. 1989 Dec;70(4):257-71. (PMID: 2626803) ; Rev Infect Dis. 1981 Sep-Oct;3(5):867-70. (PMID: 7339817) ; Am Rev Respir Dis. 1983 May;127(5):648-9. (PMID: 6846942) ; J Clin Microbiol. 1985 Feb;21(2):168-73. (PMID: 3972985) ; Annu Rev Microbiol. 1985;39:347-69. (PMID: 3904604) ; Am J Clin Pathol. 1986 Jan;85(1):67-72. (PMID: 3940423) ; Antimicrob Agents Chemother. 1985 Oct;28(4):570-5. (PMID: 4073881) ; Ann Intern Med. 1986 Aug;105(2):184-8. (PMID: 3729201) ; Rev Infect Dis. 1989 Mar-Apr;11 Suppl 2:S369-78. (PMID: 2496453) ; Rev Infect Dis. 1989 Mar-Apr;11 Suppl 2:S448-54. (PMID: 2785283) ; Clin Microbiol Rev. 1989 Oct;2(4):360-77. (PMID: 2680057) ; Am Rev Respir Dis. 1967 Jan;95(1):20-32. (PMID: 6015922) Substance Nomenclature: 0 (Antibiotics, Antitubercular) ; 0 (Rifamycins) ; 129791-92-0 (KRM 1648) ; RFM9X3LJ49 (Bilirubin) ; TDQ283MPCW (Eosine Yellowish-(YS)) ; YKM8PY2Z55 (Hematoxylin) Entry Date(s): Date Created: 19930401 Date Completed: 19930611 Latest Revision: 20210526 Update Code: 20231215 PubMed Central ID: PMC187742

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Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.