SUMMARY Clostridium difficile infection (CDI) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. In the last 2 decades, PCR- and sequence-based techniques, particularly whole-genome sequencing (WGS), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. C. difficile is taxonomically distinct from many other well-known clostridia, with a diverse population structure comprising hundreds of strain types spread across at least 6 phylogenetic clades. The C. difficile species is defined by a large diverse pangenome with extreme levels of evolutionary plasticity that has been shaped over long time periods by gene flux and recombination, often between divergent lineages. These evolutionary events are in response to environmental and anthropogenic activities and have led to the rapid emergence and worldwide dissemination of virulent clonal lineages. Moreover, genome analysis of large clinically relevant data sets has improved our understanding of CDI outbreaks, transmission, and recurrence. The epidemiology of CDI has changed dramatically over the last 15 years, and CDI may have a foodborne or zoonotic etiology. The WGS era promises to continue to redefine our view of this significant pathogen.

While Clostridium difficile infection (CDI) has come to prominence as major epidemics have occurred in North America and Europe over the recent decade, awareness and surveillance of CDI in Asia have remained poor. Limited studies performed throughout Asia indicate that CDI is also a significant nosocomial pathogen in this region, but the true prevalence of CDI remains unknown. A lack of regulated antibiotic use in many Asian countries suggests that the prevalence of CDI may be comparatively high. Molecular studies indicate that ribotypes 027 and 078, which have caused significant outbreaks in other regions of the world, are rare in Asia. However, variant toxin A-negative/toxin B-positive strains of ribotype 017 have caused epidemics across several Asian countries. Ribotype smz/018 has caused widespread disease across Japan over the last decade and more recently emerged in Korea. This review summarises current knowledge on CDI in Asian countries.

The epidemiology of Clostridium difficile infection (CDI) has changed over the past decades with the emergence of highly virulent strains. The role of asymptomatic C. difficile colonization as part of the clinical spectrum of CDI is complex because many risk factors are common to both disease and asymptomatic states. In this article, we review the role of asymptomatic C. difficile colonization in the progression to symptomatic CDI, describe the epidemiology of asymptomatic C. difficile colonization, assess the effectiveness of screening and intensive infection control practices for patients at risk of asymptomatic C. difficile colonization, and discuss the implications for clinical practice. A narrative review was performed in PubMed for articles published from January 1980 to February 2015 using search terms ‘Clostridium difficile’ and ‘colonization’ or ‘colonisation’ or ‘carriage’. There is no clear definition for asymptomatic CDI and the terms carriage and colonization are often used interchangeably. The prevalence of asymptomatic C. difficile colonization varies depending on a number of host, pathogen, and environmental factors; current estimates of asymptomatic colonization may be underestimated as stool culture is not practical in a clinical setting. Asymptomatic C. difficile colonization presents challenging concepts in the overall picture of this disease and its management. Individuals who are colonized by the organism may acquire protection from progression to disease, however they also have the potential to contribute to transmission in healthcare settings.

Clostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI–III. The emergence of these three novel genomospecies predates clades C1–5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI.

Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.