Effectiveness of Azithromycin and/or Chinese Medicine in the Early and Late Stage Infections of Shiga Toxin-Producing Escherichia coli- Infected Mouse Models

Main Author: Yunus Amran, Muhammad
Format: Article
Bahasa: eng
Terbitan: Wiley Blackwell , 2016
Subjects:
Online Access: http://repository.unhas.ac.id/handle/123456789/20715
Daftar Isi:
  • Introduction & Objectives: We developed a fatal neurological mouse model by infecting with a high dose (1010 CFU/mouse) of Shiga toxin 2c (Stx2c)-producing E. coli O157:H- strain E32511/HSC (Streptomycin and Mitomycin resistant/SMr MMCr) in 1994 (Infect Immun 62:3447 3453). Furthermore, we reported that fosfomycin and kanamycin were not effective in preventing the fatality in this animal model (FEMS Immunol Med Microbiol. 26: 101???108, 1999). Recently, Zhang et al. (J Infect Dis. 199: 486???493, 2009) reported that pediatric doses of azithromycin (AZM), but not ciprofloxacin, was effective in treating a piglet model orally infected with Stx2cproducing E. coli. In our present study, we evaluated the effectiveness of AZM and/or Chinese medicine (herbal medicine, which is known to have a purgative effect in the intestinal tract) using our mouse model inoculated with 1011 CFU/mouse of E32511/HSC (SMr MMCr) and simultaneously injected intraperitoneally with MMC, which we presumed as a late stage of EHEC infection. We also tested the effectiveness of Chinese medicine alone by using the mouse model infected with Shiga toxin 2d-producing E. coli O91:H21 strain B2F1 (Streptomycin resistant/SMr) (Infect Immun. 61:3832???3842, 1993), which we presumed as an early stage of EHEC infection. Material & Methods: ICR mice were infected with 1011 CFU/mouse of E32511/HSC (SMr MMCr), simultaneously injected intraperitoneally with MMC, thereafter treated with AZM 2, 6 or 24 h after inoculation and/or Chinese medicine 2 h after inoculation of E32511. Chinese medicine alone once per day, for five consecutive days, was given one day after oral inoculation of mouse with B2F1 (SMr) 104 CFU. Survival was observed for 2 weeks, and the data were statistically analyzed. Immunohistochemistry and pathological examinations were performed to observe the damages to mouse organs especially the brain. Results: Based on the survival rate analysis, we found that the administration of AZM in a single dose was significantly effective when given 2 h after infection compared to 6 and 24 h after infection. Moreover, administration of AZM 6 h after infection combined with Chinese medicine 2 h after infection was also effective in this mouse model inoculated with 1011 CFU of E32511/HSC (SMr MMCr). In the mouse model inoculated with 104 CFU of B2F1(SMr), treatment with Chinese medicine alone, once a day for 5 days, a day after bacterial inoculation, was significantly effective in the mouse survival and protected the colon and small intestine from bacterial adhesion. Conclusions: We found the effectiveness of AZM and its combination with Chinese medicine in our mouse model inoculated with E32511/ HSC (SMr MMCr). Moreover, only Chinese medicine was found to be effective in the mouse model inoculated with B2F1 (SMr).