Clostridium difficile: emergence of hypervirulence and fluoroquinolone resistance

Clostridium difficile is a well-known cause of sporadic and healthcare-associated diarrhea. Multihospital outbreaks due to a single strain and outbreaks associated with antibiotic selective pressure, especially clindamycin, have been well documented. Severe cases and fatalities from C. difficile are uncommon. The recent global emergence of a hypervirulent strain containing binary toxin (Toxinotype III ribotype 027), with or without deletion in a regulatory gene (tcdC gene), together with high-level resistance to third generation fluoroquinolones, has been associated with increased morbidity and mortality. Although the defective regulatory gene locus is associated with increased toxin production in vitro, the in vivo significance of this mutation and of the binary toxin remains undefined. To date, treatment strategies have not evolved in response to the emergence of this hypervirulaent strain. We provide a critical, quantitative summary of the evolving clinical and molecular epidemiology of C. difficile along with implications relevant to future treatment strategies.