Evaluation of next generation sequencing to investigate the epidemiology of Clostridium difficile infection

Clostridium difficile('C. diff') is a common cause of infectious diarrhoea following antibiotic treatment, sometimes with serious consequences. Although most cases occur in hospital in-patients, they are increasingly seen in the community, without known sources of exposure. 'C diff' can colonise the intestine prior to developing infection (CDI), and can spread between patients, causing hospital outbreaks. This was previously considered most likely due to poor hand hygiene by staff or contamination of the ward environment. More recent studies suggest many cases arise from patients own colonising 'C diff'. Knowing the source of infection is critical to future control of CDI.The proposed research programme asks, firstly, how many CDI hospital cases are caused by the patients own 'C. diff', and how many infections are caused by spread from other patients? It is technically feasible to answer this question because of newly affordable molecular technology called next-generation whole genome sequencing (WGS). WGS allows forensically accurate typing of individual 'C diff' strains down to the individual nucleotide, which helps identify their origin. We will also study strains from a sample of patients with community-acquired infection, comparing community strains; genetic similarity to hospital strains to see if, and how often, they spread within the hospital. We will also use WGS to find out if CDI recurrence is due to the patients original strain or a new infection. Knowing these patterns will allow better infection control practices.Finally, we will investigate the effects of antibiotics or a commonly used medication, proton pump inhibitors (PPIs) on healthy intestinal bacteria. We believe certain bacteria in the intestine that provide competitive exclusion against 'C diff' become depleted by these medications, facilitating further CDI. Studying the intestinal microbiota composition will identify bacteria most affected by antibiotic treatment. This will aid future treatments.

Award Date
15 May 2014
Award Value
Principal Investigator
Dr Geraldine Moloney
Host Institution
Trinity College Dublin
Research Training Fellowships for Healthcare Professionals