CLOSTRIDIUM-DIFFICILE IN GNOTOBIOTIC MICE
CLOSTRIDIUM-DIFFICILE IN GNOTOBIOTIC MICE
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DOI：
10.1128/iai.28.1.277-282.1980
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发表时间：
1980-01-01
影响因子：
3.1
通讯作者：
BARTLETT, JG
中科院分区：
文献类型：
--
作者：
ONDERDONK, AB;CISNEROS, RL;BARTLETT, JG
无菌小鼠与C. difficile [引起结肠炎相关性结肠炎的病原体]发展为肠道疾病，其特征在于固有层的多形细胞浸润、腹泻和盲肠细胞毒素浓度在10-6稀释度下呈阳性。活菌数量从未超过1010菌落形成单位[CFU]/g（干重）。尽管高毒素水平和慢性炎症超过30天，死亡率很低（< 2%）。每天用2次口服剂量的2 mg万古霉素治疗这些动物，导致粪便水平> 200 μ g/ml，远远超过对C的最小抑制浓度。很难该疗法使活细胞密度降低2-3个对数，并在第7天将孢子计数从105.8-107.8 CFU/g（干重）增加;动物没有可检测到的毒素。一旦停止治疗，活菌和孢子计数以及细胞毒素浓度恢复到先前的水平。用体外抑制浓度的克林霉素处理小鼠，对C。艰难梭菌毒素滴度或细菌计数，尽管注意到克林霉素耐药群体的出现。口服万古霉素可降低毒素浓度，而C.艰难梭菌可以作为孢子存活。相比之下，大量的营养细胞和高细胞毒素水平持续克林霉素时，即使在抑制浓度。
Germ-free mice associated with C. difficile [the pathogen responsible for antibiotic-associated colitis] developed intestinal disease characterized by polymorphonuclear cell infiltration of the lamina propria, diarrhea and cecal cytotoxin concentrations positive at a 10-6 dilution. The numbers of viable bacteria never exceeded 1010 colony-forming units [CFU]/g (dry wt). Despite the high toxin levels and chronic inflammation over 30 days, the mortality rate was low (< 2%). Daily treatment of these animals with 2 oral doses of 2 mg of vancomycin resulted in stool levels of > 200 .mu.g/ml, well in excess of the minimum inhibitory concentration for C. difficile. This therapy decreased viable cell density by 2-3 logs and increased the spore counts from 105.8-107.8 CFU/g (dry wt) by day 7; animals were free of detectable toxin. Once therapy was stopped, viable bacteria and spore counts and cytotoxin concentrations returned to previous levels. Treatment of mice with concentrations of clindamycin that were inhibitory in vitro had no effect on C. difficile toxin titers or bacterial counts, although the appearance of a clindamycin-resistant population was noted. Vancomycin, given orally, may decrease the concentration of toxin, but C. difficile may survive as spores. By contrast, large populations of vegetative cells and high cytotoxin levels persist when clindamycin is used, even at an inhibitory concentration.