Search

Clostridium ( Clostridioides ) difficile causes toxin-mediated diarrhea and pseudomembranous colitis, primarily among hospital inpatients. Outbreaks of C. difficile infection (CDI) have been caused by strains with acquired antimicrobial resistance, particularly fluoroquinolone resistance, including C. difficile ribotype (RT) 027 in North America and Europe and RT 017, the most common strain in Asia. Despite being the most common cause of hospital-acquired infection in high-income countries, and frequent misuse of antimicrobials in Asia, little is known about CDI in the Asia-Pacific region. We aimed to determine the antimicrobial susceptibility profiles of a collection of C. difficile isolates from the region. C. difficile isolates ( n  = 414) from a 2014 study of 13 Asia-Pacific countries were tested for susceptibility to moxifloxacin, amoxicillin-clavulanate, erythromycin, clindamycin, rifaximin, metronidazole, vancomycin, and fidaxomicin according to the Clinical and Laboratory Standards Institute's agar dilution method. All isolates were susceptible to metronidazole, vancomycin, amoxicillin-clavulanate, and fidaxomicin. Moxifloxacin resistance was detected in all countries except Australia, all RT 369 and QX 239 strains, and 92.7% of RT 018 and 70.6% of RT 017 strains. All C. difficile RT 012, 369, and QX 239 strains were also resistant to erythromycin and clindamycin. Rifaximin resistance was common in RT 017 strains only (63.2%) and was not detected in Australian, Japanese, or Singaporean isolates. In conclusion, antimicrobial susceptibility of C. difficile varied by strain type and by country. Multiresistance was common in emerging RTs 369 and QX 239 and the most common strain in Asia, RT 017. Ongoing surveillance is clearly warranted., (Copyright © 2020 American Society for Microbiology.)

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 facility-associated 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 third-generation 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.

Clostridioides difficile ( Clostridium difficile ) sequence type 11 (ST11) is well established in production animal populations worldwide and contributes considerably to the global burden of C. difficile infection (CDI) in humans. Increasing evidence of shared ancestry and genetic overlap of PCR ribotype 078 (RT078), the most common ST11 sublineage, between human and animal populations suggests that CDI may be a zoonosis. We performed whole-genome sequencing (WGS) on a collection of 207 ST11 and closely related ST258 isolates of human and veterinary/environmental origin, comprising 16 RTs collected from Australia, Asia, Europe, and North America. Core genome single nucleotide variant (SNV) analysis identified multiple intraspecies and interspecies clonal groups (isolates separated by ≤2 core genome SNVs) in all the major RT sublineages: 078, 126, 127, 033, and 288. Clonal groups comprised isolates spread across different states, countries, and continents, indicative of reciprocal long-range dissemination and possible zoonotic/anthroponotic transmission. Antimicrobial resistance genotypes and phenotypes varied across host species, geographic regions, and RTs and included macrolide/lincosamide resistance (Tn 6194 [ ermB ]), tetracycline resistance (Tn 6190 [ tetM ] and Tn 6164 [ tet44 ]), and fluoroquinolone resistance ( gyrA / B mutations), as well as numerous aminoglycoside resistance cassettes. The population was defined by a large "open" pan-genome (10,378 genes), a remarkably small core genome of 2,058 genes (only 19.8% of the gene pool), and an accessory genome containing a large and diverse collection of important prophages of the Siphoviridae and Myoviridae This study provides novel insights into strain relatedness and genetic variability of C. difficile ST11, a lineage of global One Health importance. IMPORTANCE Historically, Clostridioides difficile ( Clostridium difficile ) has been associated with life-threatening diarrhea in hospitalized patients. Increasing rates of C. difficile infection (CDI) in the community suggest exposure to C. difficile reservoirs outside the hospital, including animals, the environment, or food. C. difficile sequence type 11 (ST11) is known to infect/colonize livestock worldwide and comprises multiple ribotypes, many of which cause disease in humans, suggesting CDI may be a zoonosis. Using high-resolution genomics, we investigated the evolution and zoonotic potential of ST11 and a new closely related ST258 lineage sourced from diverse origins. We found multiple intra- and interspecies clonal transmission events in all ribotype sublineages. Clones were spread across multiple continents, often without any health care association, indicative of zoonotic/anthroponotic long-range dissemination in the community. ST11 possesses a massive pan-genome and numerous clinically important antimicrobial resistance elements and prophages, which likely contribute to the success of this globally disseminated lineage of One Health importance., (© Crown copyright 2019.)