Use of vancomycin hydrochloride for treatment of Clostridium difficile enteritis in Syrian hamsters
Boss, S.M.; Gries, C.L.; Kirchner, B.K.; Smith, G.D.; Francis, P.C.
Laboratory Animal Science 44(1): 31-37
1994
ISSN/ISBN: 0023-6764 PMID: 8007657 Document Number: 426117
As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic-induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 ( lt 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects. Since no detectable concentrations of vancomycin were present in the plasma of hamsters after oral dosing, these findings suggest that long-term vancomycin treatment does not result in systemic exposure in hamsters but can protect against fatal C. difficile enteritis.