Abstract
The etiology of C. difficile infection is primarily through contact of the pathogen to an intestinal milieu perturbed by exposure to antimicrobials. We have evaluated the relative abilities of 14 widely used antimicrobials to initiate a terminal infection in a modified hamster model of C. difficile disease. Animals were exposed to a highly toxinogenic strain of C. difficile for 10 days and were dosed with antibiotics for 5 days. Our results showed that orally administered clindamycin, amoxicillin, amoxicillin/clavulanate, and ampicillin initiated early onset disease that occurred during the 5 days of antibiotic dosing. Parenterally administered imipenem and ceftriaxone initiated disease within the first 2 days of dosing. Late onset disease (1-5 days after cessation of dosing) occurred in animals receiving the oral drugs, erythromycin, clarithromycin, and ciprofloxacin and in animals receiving parenterally administered piperacillin, piperacillin/tazobactam, ampicillin/sulbactam, and ciprofloxacin. No symptoms or C. difficile toxin A was evident in metronidazole treated, vancomycin treated or control animals not receiving antibiotics. Cecal antibiotic levels were below the MIC values for C. difficile but resulted in a perturbed intestinal microflora as evidenced by elevated cecal weights. This hamster model may be a useful model to study antibiotics relative to their risk of initiating early or late onset C. difficile disease in humans.