Quantitative study of antibiotic-induced susceptibility to Clostridium difficile enterocecitis in hamsters

Commonly used antibiotics were compared for their ability to induce Clostridium difficile enterocecitis and death in hamsters. Susceptibility to infection with C. difficile was measured by calculating 50% lethal doses (in CFU) for hamsters for various intervals after antibiotic treatment. Infection occurred after very small doses of C. difficile were given to hamsters treated with clindamycin, ampicillin, flucloxacillin, and cefuroxime; there was little difference between the antibiotics in the degree of susceptibility that they induced. A large difference in the duration of susceptibility was observed, however, with susceptibility being temporary following ampicillin, flucloxacillin, and cefuroxime administration but long-lived following clindamycin administration. A larger dose of ampicillin, multiple doses of ampicillin, and a combination of antibiotics had comparatively small effects on the duration of susceptibility. C. difficile growth and toxin production in in vitro suspensions of cecal contents were found to correlate closely with in vivo hamster infectivity. A persisting loss of colonization resistance following antibiotic treatment may be a type of postantibiotic effect. Although these results cannot be applied directly to humans, they suggest lines of further investigation into how antibiotics may differ in producing risks of C. difficile infection and pseudomembranous colitis in patients.