Abstract
The global emergence and dissemination of epidemic Clostridioides difficile ribotype 027 (RT027) and related lineages illustrate the role of antimicrobial pressure in shaping the epidemiology of this pathogen. We propose a hierarchical model in which fluoroquinolones (FQs) served as the dominant selective force underlying the worldwide expansion of RT027-related strains, with rifampin and rifamycins acting as secondary modifiers that promoted persistence and regional dominance.