Clostridium (Now Closteroides) difficile Spore Formation Is Higher in Epidemic Isolates When Treated With Vancomycin in Vivo and in Vitro

Abstract

Between 2000-2007, Clostridium (now Closteroides) difficile infections have increased by a factor of 400% and have been associated with greater disease severity. These increases are associated to the increased prevalence of the NAP1/BI/027 ribotype (ribotype-027). This ribotype was characterized as hypervirulent, and one reason was the ability to produce greater numbers of spores in vitro. However, it is unclear whether the epidemic ribotype-027 are able to produce greater numbers of spores in vivo, and if this plays a role during clinically relevant treatments. To determine if epidemic strains are able to produce more spores during clinically relevant treatments, the growth and in vivo production of spores of four C. difficile isolates (2 non-epidemic and 2-epidemic) were determined in the hamster model of C. difficile infection (CDI). By using this model, the epidemic isolates of C. difficile were found to produce more spores than the non-epidemic isolates during treatment with vancomycin. The difference in spore numbers in response to the presence of vancomycin also occurred in in vitro cultures. These differences between the epidemic and non-epidemic isolates were consistent despite there being no difference to sensitivity to vancomycin in vitro. Thus, antibiotic treatment promoted higher levels of spores of epidemic isolates in vivo and in vitro than found in non-epidemic isolates, suggesting this difference in response to clinically relevant antibiotics is a factor that contributes to the ribotype-027 being more frequently diagnosed in C. difficile cases.