Objective: To determine whether PPI administration to hamsters (a well studied model of antibiotic-associated CDI) render these animals susceptable to colonization and/or disease following challenge with toxigenic Clostridium difficile (CD).
Methods: Esomeprazole (ESO) in bicarbonate buffer was administered orally to groups of 10 hamsters, followed by oral challenge with spores of the epidemic CD strain BI17. Fecal pellets were collected and cultured semi-quantitatively on selective CD medium daily for the first week after challenge with CD, then biweekly for one week and weekly thereafter. All animals were monitored for colonization and disease for 30 days. At least 2 negative control hamsters (given bicarbonate, but no PPI, followed by BI17 challenge) and 2 positive control hamsters (given oral clindamycin followed five days later by BI17 challenge) were included in each experiment.
Results: Pilot studies confirmed that 25 mg/kg ESO caused a physiologic effect increasing stomach pH from 2.5 to 3.9. In the first experiment, 10 hamsters received oral ESO at 25 mg/kg daily for 4 days followed by 10,000 BI17 spores on day five. None of these hamsters or negative control hamsters had detectable colonies of CD in their pellets or signs of disease following BI17 challenge. In the second experiment, 10 hamsters received oral ESO at 50 mg/kg daily for 7 days and were administered 1 million BI17 spores on day 5 (during continued PPI administration). Nine of 10 hamsters (90%) had fecal pellet cultures positive for CD up to 48 hours after spore challenge: 6 had detectable CD 24 hours and 7 had CD detectable 48 hours after challenge. Among culture-positive hamsters, colony counts were low (1 to 2 plate quadrants) at 24 hours and rare (1 to 5 colonies) at 48 hours. At 72 hours after challenge and later, no CD colonies were detected. None of these hamsters exhibited disease symptoms. Negative control hamsters who received the same BI17 challenge but no PPI had no detectable CD in their fecal pellets or subsequent disease. The positive control hamsters had detectable CD in their fecal pellets 24 hours post-BI17 challenge, and died 1-4 days later.
Conclusions: C. difficile colonies were detected at low levels in fecal pellets of hamsters given the higher dose of esomeprazole and challenged during esomeprazole administration with a higher inoculum of the epidemic BI17 strain. Despite transient appearance of C. difficile in the feces, hamsters did not develop disease. It is possible that PPIs facilitate C. difficile proliferation in the intestine, but are not sufficient alone to render the host susceptible to CDI.