Clostridium difficile infection (CDI) is a major cause of infectious diarrhoea and colitis following antibiotic treatment. It is mostly diagnosed in hospitalised patients but an increasing proportion of cases, 17%, are reported to originate in the community. CDI prevention continues to be a priority for infection control teams. Up to 20% of first infections subsequently recur. This may be either a relapse due to the original strain or a newly acquired strain. Detailed resolution of C difficile epidemiology is now achievable through whole genome sequence (WGS) analysis. Current infection control practice is informed by DNA based ribotyping of strains but this method is far less discriminatory than WGS. New strains are constantly appearing; in the applicant’s hospital, ribotypes 078 and 020 are now more commonly identified than the previously predominant ribotype 027 strain.
We will undertake whole genome sequencing for all C difficile isolates on a prospective basis in the hospital over a two-year period using an Illumina MiSeq instrument. We will identify related strains, and use clinical information to identify novel targets for infection control. We will analyse similarity of hospital and community-acquired strains, and identify recurrent episodes as molecular relapses or re-infections.
Antibiotics, and likely also proton pump inhibitors, are known to disrupt the intestinal microbiome. Several independent studies, including research by the applicants in a murine model, have established links between antibiotic mediated perturbation of the gut microbiota and CDI. We will employ next-generation sequencing as a means to analyse patients’ intestinal microbiota by 16S ribosomal gene amplicon sequencing in a prospective cohort study comparing patients with single-episode CDI with those who suffer recurrent infections. This research should add important evidence to support future biotherapeutic approaches and identify changes in gut microbial diversity and composition associated with clinical outcome.
