Oka Kentaro, Osaki Takako, Hanawa Tomoko, Kurata Satoshi, Sugiyama Emi, Takahashi Motomichi, Tanaka Mamoru, Taguchi Haruhiko, Kamiya Shigeru
Tokyo R&D Center, Miyarisan Pharmaceutical Co., Ltd., Tokyo, Japan.
Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
Front Microbiol. 2018 Jun 18;9:1264. doi: 10.3389/fmicb.2018.01264. eCollection 2018.
is well known as an agent responsible for pseudomembranous colitis and antibiotic-associated diarrhea. The hamster model utilizing an oral route for infection of has been considered to be the standard model for analysis of infection (CDI) but this model exhibits differences to human CDI, most notably as most hamsters die without exhibiting diarrhea. Therefore, we attempted to develop a new non-lethal and diarrheal rat CDI model caused by endogenous using metronidazole (MNZ) and egg white. In addition, the effects of probiotic strain MIYAIRI 588 (CBM) on CDI were examined using this model. Syrian Golden hamsters received clindamycin phosphate orally at 30 mg/kg on 5 days before challenge with either VPI10463 (hypertoxigenic strain) or KY34 (low toxigenic clinical isolate). Mortality and the presence of diarrhea were observed twice a day for the duration of the experiment. Wistar rats received 10% egg white dissolved in drinking water for 1 week following intramuscular administration of 200 mg/kg MNZ twice a day for 3 days. Diarrhea score was determined for each day and fecal water content, biotin concentration, and cytotoxin titer in feces were examined. More than 70% of hamsters orally infected with died without exhibiting diarrhea regardless of toxigenicity of strain. The rats receiving egg white after MNZ administration developed diarrhea due to overgrowth of endogenous . This CDI model is non-lethal and diarrheal, and some rats in this model were spontaneously cured. The incidence of diarrhea was significantly decreased in treated rats. These results indicate that the CDI model using egg white and MNZ has potentially better similarity to human CDI, and implies that treatment with may reduce the risk of CDI.
作为导致伪膜性结肠炎和抗生素相关性腹泻的病原体而广为人知。利用口服途径感染仓鼠的模型一直被认为是分析艰难梭菌感染(CDI)的标准模型,但该模型与人类CDI存在差异,最显著的是大多数仓鼠在未出现腹泻的情况下死亡。因此,我们试图开发一种由内源性艰难梭菌引起的新的非致死性腹泻大鼠CDI模型,使用甲硝唑(MNZ)和蛋清。此外,使用该模型研究了益生菌菌株宫入588(CBM)对CDI的影响。叙利亚金仓鼠在接受VPI10463(高毒力菌株)或KY34(低毒力临床分离株)攻击前5天,口服30mg/kg磷酸克林霉素。在实验期间,每天观察两次死亡率和腹泻情况。Wistar大鼠在每天两次肌肉注射200mg/kg MNZ,持续3天后,饮用含10%蛋清的饮用水1周。每天测定腹泻评分,并检测粪便含水量、生物素浓度和粪便中的细胞毒素滴度。无论菌株的毒力如何,超过70%口服感染艰难梭菌的仓鼠在未出现腹泻的情况下死亡。MNZ给药后接受蛋清的大鼠因内源性艰难梭菌过度生长而出现腹泻。这种CDI模型是非致死性且腹泻的,该模型中的一些大鼠可自发治愈。用宫入588治疗的大鼠腹泻发生率显著降低。这些结果表明,使用蛋清和MNZ的CDI模型与人类CDI可能具有更好的相似性,并且表明用宫入588治疗可能会降低CDI的风险。