INVITRO AND INVIVO EVALUATION OF TIACUMICIN-B AND TIACUMICIN-C AGAINST CLOSTRIDIUM-DIFFICILE

被引:83
作者
SWANSON, RN
HARDY, DJ
SHIPKOWITZ, NL
HANSON, CW
RAMER, NC
FERNANDES, PB
CLEMENT, JJ
机构
关键词
D O I
10.1128/AAC.35.6.1108
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Tiacumicins B and C are members of a novel group of 18-membered macrolide antibiotics with in vitro activity against Clostridium difficile. The MICs against 15 strains of C. difficile were 0.12 to 0.25-mu-g/ml for tiacumicin B, 0.25 to 1-mu-g/ml for tiacumicin C, and 0.5 to 1-mu-g/ml for vancomycin. The resistance frequency for both compounds against C. difficile was < 2.8 x 10(-8) at four and eight times the MIC. The in vivo activities of the tiacumicins against two strains of C. difficile were compared with that of vancomycin in a hamster model of antibiotic-associated colitis. Oral therapy with 0.2, 1, or 5 mg of 5 mg of tiacumicin B or C per kg of body weight protected 100 % of clindamycin-treated hamsters exposed to C. difficile ATCC 9689. Oral treatment with identical doses of vancomycin produced a prolonged, dose-dependent survival of hamsters, but it did not prevent the development of fatal colitis at doses of up to 5 mg/kg. When clindamycin-treated animals were exposed to another strain of C. difficile, both tiacumicin B and vancomycin were protective at 5 mg/kg, but not at lower doses. Tiacumicin C was not tested in vivo against the second strain of C. difficile. No tiacumicin B or C was detected in the sera of hamsters treated with single oral doses of 25 mg/kg, while antibiotic levels in the ceca of these hamsters reached 248-mu-g/ml and 285 mg/ml for tiacumicins B and C, respectively. The tiacumicins demonstrated in vitro and in vivo potencies against C. difficile and achieved high concentrations in the cecum, but not the serum, of hamsters after oral administration.
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页码:1108 / 1111
页数:4
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