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.

Clostridium difficile PCR ribotype (RT) 014 is well-established in both human and porcine populations in Australia, raising the possibility that C. difficile infection (CDI) may have a zoonotic or foodborne etiology. Here, whole genome sequencing and high-resolution core genome phylogenetics were performed on a contemporaneous collection of 40 Australian RT014 isolates of human and porcine origin. Phylogenies based on MLST (7 loci, STs 2, 13, and 49) and core orthologous genes (1260 loci) showed clustering of human and porcine strains indicative of very recent shared ancestry. Core genome single nucleotide variant (SNV) analysis found 42% of human strains showed a clonal relationship (separated by ≤2 SNVs in their core genome) with one or more porcine strains, consistent with recent inter-host transmission. Clones were spread over a vast geographic area with 50% of the human cases occurring without recent healthcare exposure. These findings suggest a persistent community reservoir with long-range dissemination, potentially due to agricultural recycling of piggery effluent. We also provide the first pan-genome analysis for this lineage, characterizing its resistome, prophage content, and in silico virulence potential. The RT014 is defined by a large “open” pan-genome (7587 genes) comprising a core genome of 2296 genes (30.3% of the total gene repertoire) and an accessory genome of 5291 genes. Antimicrobial resistance genotypes and phenotypes varied across host populations and ST lineages and were characterized by resistance to tetracycline [tetM, tetA(P), tetB(P) and tetW], clindamycin/erythromycin (ermB), and aminoglycosides (aph3-III-Sat4A-ant6-Ia). Resistance was mediated by clinically important mobile genetic elements, most notably Tn6194 (harboring ermB) and a novel variant of Tn5397 (harboring tetM). Numerous clinically important prophages (Siphoviridae and Myoviridae) were identified as well as an uncommon accessory gene regulator locus (agr3). Conservation in the pathogenicity locus and S-layer correlated with ST affiliation, further extending the concept of clonal C. difficile lineages. This study provides novel insights on the genetic variability and strain relatedness of C. difficile RT014, a lineage of emerging One Health importance. Ongoing molecular and genomic surveillance of strains in humans, animals, food, and the environment is imperative to identify opportunities to reduce the overall CDI burden.

Clostridium difficile ribotype (RT) 017 is an important toxigenic C. difficile RT which, due to a deletion in the repetitive region of the tcdA gene, only produces functional toxin B. Strains belonging to this RT were initially dismissed as nonpathogenic and circulated largely undetected for almost two decades until they rose to prominence following a series of outbreaks in the early 2000s. Despite lacking a functional toxin A, C. difficile RT 017 strains have been shown subsequently to be capable of causing disease as severe as that caused by strains producing both toxins A and B. While C. difficile RT 017 strains can be found in almost every continent today, epidemiological studies suggest that the RT is endemic in Asia and that the global spread of this MLST clade 4 lineage member is a relatively recent event. C. difficile RT 017 transmission appears to be mostly from human to human with only a handful of reports of isolations from animals. An important feature of C. difficile RT 017 strains is their resistance to several antimicrobials and this has been documented as a possible factor driving multiple outbreaks in different parts of the world. This review summarizes what is currently known regarding the emergence and evolution of strains belonging to C. difficile RT 017 as well as features that have allowed it to become an RT of global importance.

Clostridioides difficile causes healthcare-related diarrhoea in high-income countries. Highly resistant spores persist in healthcare facilities, primarily infecting patients who have recently received antimicrobials. C. difficile infection (CDI) has been studied in detail in North America and Europe; however, the epidemiology of CDI elsewhere, including the Asia-Pacific region, is largely unknown. A survey of CDI was performed in 13 Asia-Pacific countries. Epidemiological data on 600 cases were collected and molecular typing undertaken on 414 C. difficile isolates. Healthcare facilityassociated CDI comprised 53.6% of cases, while community-associated CDI was 16.5%. The median age of cases was 63.0 years and 45.3% were female, 77.5% had used antibiotics in the previous 8 weeks, most frequently thirdgeneration cephalosporins (31.7%), and 47.3% had used proton pump inhibitors. Recurrence (9.1%) and mortality (5.2%) rates were low, while complications including colitis or pseudomembranous colitis (13.8%), colectomy (0.4%), and toxic megacolon (0.2%) were uncommon. Common C. difficile strains were ribotypes 017 (16.7%), 014/020 (11.1%) and 018 (9.9%), with wide variation between countries. Binary toxin-positive strains of C. difficile were detected rarely. Overall, disease severity appeared mild, and mortality and recurrence were low. Continued education about, and surveillance of, CDI in Asia are required to reduce the burden of disease.

Clostridium difficile has not been studied in detail in Asia, particularly Southeast Asia. We thus performed a prevalence study across four hospitals in Central Java province, Indonesia. Stool samples were collected from patients with diarrhoea and tested by enzyme immunoassay for glutamate dehydrogenase (GDH) and toxin A/B (C DIFF QUIK CHEK COMPLETE, TechLab). Specimens were cultured and molecular typing was performed. In total, 340 samples were tested, of which 70 (20.6%) were GDH positive, with toxin detected in 19 (5.6%). Toxigenic C. difficile was isolated from 37 specimens (10.9%), while a further 36 (10.6%) nontoxigenic isolates were identified. The most common strain was ribotype 017 (24.3% of 74 isolates), followed by nontoxigenic types QX 224 (9.5%), and QX 238 and QX 108 (both 8.1%). The high prevalence of C. difficile highlights a need for ongoing surveillance of C. difficile infection in Indonesia.

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The epidemiology of Clostridium difficile infection (CDI) has changed over time and between countries. It is therefore essential to monitor the characteristics of patients at risk of infection and the circulating strains to recognize local and global trends, and improve patient management. From December 2011 to May 2012 we conducted a prospective, observational epidemiological study of patients with laboratory-confirmed CDI at two tertiary teaching hospitals in Perth, Western Australia to determine CDI incidence and risk factors in an Australian setting. The incidence of CDI varied from 5.2 to 8.1 cases/10 000 occupied bed days (OBDs) at one hospital and from 3.9 to 16.3/10 000 OBDs at the second hospital. In total, 80 patients with laboratory-confirmed CDI met eligibility criteria and consented to be in the study. More than half (53.8%) had hospital-onset disease, 28.8% had community-onset and healthcare facility-associated disease and 7.5% were community-associated infections according to the definitions used. Severe CDI was observed in 40.0% of these cases but the 30-day mortality rate for all cases was only 2.5%. Besides a shorter length of stay among cases of community-onset CDI, no characteristics were identified that were significantly associated with community-onset or severe CDI. From 70 isolates, 34 different ribotypes were identified. The predominant ribotypes were 014 (24.3%), 020 (5.7%), 056 (5.7%) and 070 (5.7%). Whereas this study suggests that the characteristics of CDI cases in Australia are not markedly different from those in other developed countries, the increase in CDI rate observed emphasizes the importance of surveillance.

We used multilocus sequence typing and variable number tandem repeat analysis to determine the clonal origins of Vibrio cholerae O1 El Tor strains from an outbreak of cholera that began in 2009 in Papua New Guinea. The epidemic is ongoing, and transmission risk is elevated within the Pacific region.