What is the role of antimicrobial resistance in the new epidemic of Clostridium difficile?

The epidemiology of Clostridium difficile infection (CDI) has changed in recent years, with the occurrence of large outbreaks of infection associated with the emergence of 'hypervirulent' strains, particularly PCR ribotype 027. There has been much speculation as to the nature of the factors responsible for driving the new epidemic of CDI, and various hypotheses have been proposed. These include increases in the size of the population at risk of CDI and/or their susceptibility to infection, increased exposure to the organism, and changes in the virulence/ transmissibility of the pathogen. Resistance to a range of antimicrobial agents, including the fluoroquinolones, is a common feature of these newly emerged strains. This article considers the part antimicrobial resistance may play as a driver for the observed changes in the epidemiology of CDI and presents a model that would support such a role. However, the paucity of definitive evidence for a causal role and the complexity of the epidemiology of CDI are acknowledged. It may be more accurate to view antimicrobial resistance as one of a range of factors which interact to alter the parameters of the 'CDI equation', and thereby determine the size of the CDI problem associated with any given emerging subtype of C. difficile.