Genomic investigation of a sequence type 67 Clostridium difficile causing community-acquired fulminant colitis in Hong Kong

INTRODUCTION Clostridium difficile has been an increasing problem in UK hospitals. At the time of this study, there was a high incidence of C. difficile within our trust and a number of patients developed acute fulminant colitis requiring subtotal colectomy. We review a series of colectomies for C. difficile, examining the associated morbidity and mortality and the factors that predispose to acute fulminant colitis. PATIENTS AND METHODS This is a retrospective study of patients undergoing subtotal colectomy for C. difficile colitis in an NHS trust over 18 months. Case notes were reviewed for antibiotic use, duration of diarrhoea, treatment, blood results, pre-operative imaging and surgical morbidity and mortality. RESULTS A total of 1398 patients tested positive for C. difficile in this period. Of these, 18 (1.29%) underwent colectomy. All were emergency admissions, 35% medical, 35% surgical, 24% neurosurgical and 6% orthopaedic. In the cohort, 29% were aged less than 65 years. Patients had a median of three antibiotics (range, 1–6), for a median of 10 days (range, 0–59 days). Median length of stay prior to C. difficile diagnosis was 13 days. Subtotal colectomy was performed a median of 4 days (range, 0–23 days) after diagnosis. Postoperative mortality was 53% (9 of 17). The median C-reactive protein level for those who died was 302 mg/l, in contrast to 214 mg/l in the survival group. Whilst 62% of all C. difficile cases were medical, the colectomy rate was only 0.7%. In the surgical specialties, the colectomy rates were 3.2% for general surgical, 1.2% for orthopaedic and 8% for neurosurgical patients. CONCLUSIONS Colectomy for C. difficile colitis has a high mortality but can be life-saving, even in extremely sick patients. Although heavy antibiotic use is a predisposing factor, this is not an obligatory prerequisite in the development of C. difficile. Neither is it a disease of the elderly, making it difficult to predict vulnerable patients. There are large differences in colectomy rates between specialties and we suggest there may be a place for a surgical opinion in all cases of severe C. difficile colitis.

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Phenotypic characterisation of Clostridium difficile PCR ribotype 251, an emerging multi-locus sequence type clade 2 strain in Australia

Anaerobe ◽

10.1016/j.anaerobe.2019.06.019 ◽

2019 ◽

Vol 60 ◽

pp. 102066 ◽

Cited By ~ 2

Author(s):

Stacey Hong ◽

Daniel R. Knight ◽

Barbara Chang ◽

Robert J. Carman ◽

Thomas V. Riley

Keyword(s):

Clostridium Difficile ◽

Sequence Type ◽

Phenotypic Characterisation

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Typing of Clostridium difficile isolates endemic in Japan by sequencing of slpA and its application to direct typing

Journal of Medical Microbiology ◽

10.1099/jmm.0.016147-0 ◽

2010 ◽

Vol 59 (5) ◽

pp. 556-562 ◽

Cited By ~ 33

Author(s):

Haru Kato ◽

Hideaki Kato ◽

Yoichiro Ito ◽

Takayuki Akahane ◽

Sayuri Izumida ◽

...

Keyword(s):

Clostridium Difficile ◽

Protein A ◽

Sequence Type ◽

Typing System ◽

Pcr Ribotyping ◽

Stool Specimens ◽

Encoding Gene ◽

Ribotype 078 ◽

Toxic Culture ◽

Pcr Ribotype 027

A typing system for Clostridium difficile using sequencing of the surface-layer protein A encoding gene (slpA) was evaluated and used to analyse clinical isolates in Japan. A total of 160 stool specimens from symptomatic patients in Japan was examined and 87 C. difficile isolates were recovered. slpA sequence typing was found to have reliable typability and discriminatory power in comparison with PCR ribotyping, and the typing results were highly reproducible and comparable. slpA sequence typing was used to type C. difficile in DNA extracted directly from stool specimens. Among the 90 stool specimens in which direct typing results were obtained, 77 specimens were positive for C. difficile culture, and typing results from isolated strains agreed with those from direct typing in all 77 specimens. The slpA sequence type smz was dominant at all four hospitals examined, and this endemic type was detected by culture and/or direct typing in 61 (62 %) of 99 stool specimens positive for toxic culture and/or direct slpA sequence typing. Comparison of epidemic strains reported throughout the world revealed one isolate identified as slpA sequence type gc8, which was found to correspond to PCR ribotype 027 (BI/NAP1/027), whereas no isolates were found with the slpA gene identical to that of PCR ribotype 078 strain. slpA sequence typing is valuable for comparison of C. difficile strains epidemic in diverse areas because the typing results are reproducible and can easily be shared. In addition, slpA sequence typing could be applied to direct typing without culture.

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Evolutionary and Genomic Insights intoClostridioides difficileSequence Type 11: a Diverse Zoonotic and Antimicrobial-Resistant Lineage of Global One Health Importance

mBio ◽

10.1128/mbio.00446-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 22

Author(s):

Daniel R. Knight ◽

Brian Kullin ◽

Grace O. Androga ◽

Frederic Barbut ◽

Catherine Eckert ◽

...

Keyword(s):

Clostridium Difficile ◽

Antimicrobial Resistance ◽

Long Range ◽

One Health ◽

Core Genome ◽

Sequence Type ◽

Content Type ◽

Pan Genome ◽

Clostridioides Difficile ◽

Animal Populations

ABSTRACTClostridioides difficile(Clostridium difficile) sequence type 11 (ST11) is well established in production animal populations worldwide and contributes considerably to the global burden ofC. difficileinfection (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 (Tn6194[ermB]), tetracycline resistance (Tn6190[tetM] and Tn6164[tet44]), and fluoroquinolone resistance (gyrA/Bmutations), 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 theSiphoviridaeandMyoviridae. This study provides novel insights into strain relatedness and genetic variability ofC. difficileST11, a lineage of global One Health importance.IMPORTANCEHistorically,Clostridioides difficile(Clostridium difficile) has been associated with life-threatening diarrhea in hospitalized patients. Increasing rates ofC. difficileinfection (CDI) in the community suggest exposure toC. difficilereservoirs outside the hospital, including animals, the environment, or food.C. difficilesequence 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.

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