Clostridium difficile in gnotobiotic mice

A. B. Onderdonk, R. L. Cisneros, J. G. Bartlett

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Germfree mice associated with Clostridium difficile 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 per g (dry weight). Despite the high toxin levels and chronic inflammation over a 30-day period, the mortality rate was low (<2%). Daily treatment of these animals with two oral doses of 2 mg of vancomycin resulted in stool levels of >200 μg/ml, well in excess of the minimum inhibitory concentration for C. difficile. This therapy decreased viable cell density by 2 to 3 logs and increased the spore counts from 105.8 to 107.8 colony-forming units per g (dry weight) by day 7, and animals were free of detectable toxin. However, once therapy was stopped, viable bacteria and spore counts and cytotoxin concentrations returned to previous levels. Treatment of mice with concentrations of clinidamycin shown to be inhibitory in vitro had no effect on C. difficile toxin titers or bacterial counts, although the appearance of a clindamycin-resistant population was noted. These data indicate that vancomycin, given orally, decreases the concentration of toxin, but C. difficile survive as spores. By contrast, large populations of vegetative cells and high cytotoxin levels persist when clindamycin is used, even at an inhibitory concentration.

Original languageEnglish (US)
Pages (from-to)277-282
Number of pages6
JournalInfection and immunity
Issue number1
StatePublished - 1980
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


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