THERAPEUTIC EFFICACY OF THE BENZOXAZINORIFAMYCIN KRM-1648 AGAINST EXPERIMENTAL MYCOBACTERIUM-AVIUM INFECTION INDUCED IN RABBITS

被引:22
作者
EMORI, M
SAITO, H
SATO, K
TOMIOKA, H
SETOGAWA, T
HIDAKA, T
机构
[1] SHIMANE MED UNIV,SCH MICROBIOL & IMMUNOL,IZUMO,SHIMANE 693,JAPAN
[2] SHIMANE MED UNIV,DEPT OPHTHALMOL,IZUMO,SHIMANE 693,JAPAN
[3] KANEKA CORP,BIOCHEM RES LABS,TAKASAGO,HYOGO 676,JAPAN
关键词
D O I
10.1128/AAC.37.4.722
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:722 / 728
页数:7
相关论文
共 36 条
[1]  
ARMSTRON.AL, 1967, AM REV RESPIR DIS, V95, P20
[2]  
BACA ME, 1989, IMMUNOLOGY, V66, P131
[3]   TREATMENT OF DISSEMINATED MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN AIDS WITH AMIKACIN, ETHAMBUTOL, RIFAMPIN, AND CIPROFLOXACIN [J].
CHIU, J ;
NUSSBAUM, J ;
BOZZETTE, S ;
TILLES, JG ;
YOUNG, LS ;
LEEDOM, J ;
HESELTINE, PNR ;
MCCUTCHAN, JA .
ANNALS OF INTERNAL MEDICINE, 1990, 113 (05) :358-361
[5]  
DANNENBERG AM, 1989, REV INFECT DIS, V11, pS369
[6]   ACTIVITY OF CLARITHROMYCIN AGAINST MYCOBACTERIUM-AVIUM INFECTION IN PATIENTS WITH ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME - A CONTROLLED CLINICAL-TRIAL [J].
DAUTZENBERG, B ;
TRUFFOT, C ;
LEGRIS, S ;
MEYOHAS, MC ;
BERLIE, HC ;
MERCAT, A ;
CHEVRET, S ;
GROSSET, J .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1991, 144 (03) :564-569
[7]  
DURR FE, 1959, AM REV RESPIR DIS, V80, P876
[8]   PATHOLOGICAL FINDINGS IN DISSEMINATED MYCOBACTERIUM AVIUM-INTRACELLULAR INFECTION - A REPORT OF 11 CASES [J].
FARHI, DC ;
MASON, UG ;
HORSBURGH, CR .
AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 1986, 85 (01) :67-72
[9]   INVITRO AND INVIVO ACTIVITIES OF CLARITHROMYCIN AGAINST MYCOBACTERIUM-AVIUM [J].
FERNANDES, PB ;
HARDY, DJ ;
MCDANIEL, D ;
HANSON, CW ;
SWANSON, RN .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1989, 33 (09) :1531-1534
[10]   AN ACUTE INFECTION MODEL FOR MYCOBACTERIUM-INTRACELLULARE DISEASE USING BEIGE MICE - PRELIMINARY-RESULTS [J].
GANGADHARAM, PR ;
EDWARDS, CK ;
MURTHY, PS ;
PRATT, PF .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1983, 127 (05) :648-649