Genome-Based Infection Tracking Reveals Dynamics of Clostridium difficile Transmission and Disease Recurrence.
BACKGROUND
Accurate tracking of Clostridium difficile transmission within healthcare settings is key to its containment but is hindered by the lack of discriminatory power of standard genotyping methods. We describe a whole-genome phylogenetic-based method to track the transmission of individual clones in infected hospital patients from the epidemic C. difficile 027/ST1 lineage, and to distinguish between the 2 causes of recurrent disease, relapse (same strain), or reinfection (different strain).


METHODS
We monitored patients with C. difficile infection in a UK hospital over a 2-year period. We performed whole-genome sequencing and phylogenetic analysis of 108 strains isolated from symptomatic patients. High-resolution phylogeny was integrated with in-hospital transfers and contact data to create an infection network linking individual patients and specific hospital wards.


RESULTS
Epidemic C. difficile 027/ST1 caused the majority of infections during our sampling period. Integration of whole-genome single nucleotide polymorphism (SNP) phylogenetic analysis, which accurately discriminated between 27 distinct SNP genotypes, with patient movement and contact data identified 32 plausible transmission events, including ward-based contamination (66%) or direct donor-recipient contact (34%). Highly contagious donors were identified who contributed to the persistence of clones within distinct hospital wards and the spread of clones between wards, especially in areas of intense turnover. Recurrent cases were identified between 4 and 26 weeks, highlighting the limitation of the standard <8-week cutoff used for patient diagnosis and management.


CONCLUSIONS
Genome-based infection tracking to monitor the persistence and spread of C. difficile within healthcare facilities could inform infection control and patient management.
['Kumar|Nitin|N|', 'Miyajima|Fabio|F|', 'He|Miao|M|', 'Roberts|Paul|P|', 'Swale|Andrew|A|', 'Ellison|Louise|L|', 'Pickard|Derek|D|', 'Smith|Godfrey|G|', 'Molyneux|Rebecca|R|', 'Dougan|Gordon|G|', 'Parkhill|Julian|J|', 'Wren|Brendan W|BW|', 'Parry|Christopher M|CM|', 'Pirmohamed|Munir|M|', 'Lawley|Trevor D|TD|']
D000328:Adult D016360:Clostridioides difficile D003015:Clostridium Infections D003428:Cross Infection D004196:Disease Outbreaks D005260:Female D016680:Genome, Bacterial D005838:Genotype D006760:Hospitalization D006801:Humans D008297:Male D008875:Middle Aged D010802:Phylogeny D020641:Polymorphism, Single Nucleotide D012008:Recurrence D021521:Ribotyping D017422:Sequence Analysis, DNA D006113:United Kingdom D055815:Young Adult
recurrence C. difficile 027/ST1 whole-genome sequencing highly contagious individuals ward-based transmission