Clostridium difficile infection (CDI), caused by the headline grabbing, potentially fatal “superbug”, is one of the most common healthcare-acquired infections. At this scientific session from the UK Bioscience Forum, public health and industry experts described the challenges in controlling CDI, as well as promising clinical approaches to prevent and treat it.
From January 2004 to July 2014, CDI is estimated to have cost £1 billion to patients and the NHS, including reputational damage and loss of confidence. Dr Patel, Consultant Medical Microbiologist, Public Health England and Honorary Consultant Medical Microbiologist, Barts Health NHS Trust, described CDI as creating “a decade of suffering” for patients.
C.difficile, also known as C.diff, can cause diarrhoea, intestinal inflammation and serious illness, with 10% mortality rate in patients whose gut flora have been disrupted by antibiotics. During its peak in 2007, close to 60,000 cases were reported in England, Wales and Northern Ireland. As a spore-forming bacterium, C.diff spores can survive several years and spread easily.
The number of cases in hospitals has declined dramatically since the introduction in 2004 of mandatory surveillance of both C.diff and Methicillin-resistant Staphylococcus aureus, with 6,000 CDI cases reported in the financial year ending March 2013.1 Nonetheless, levels could fall by a further 20% by improving antimicrobial prescribing, Dr Patel believes.
The importance of tackling over-prescribing and misuse of antibiotics was reiterated by Dr Paul Cotter, Principal Investigator, Alimentary Pharmabiotic Centre and Permanent Researcher, Teagasc Food Research Centre, Cork, Ireland. His team has been researching bacteriocins, made by non-pathogenic bacteria, as a new approach to treating CDI.
Dr Cotter’s team found that the bacteriocin thuricin was a promising candidate against C.diff. Antibiotics and some bacteriocins act as “weapons of mass destruction”, said Dr Cotter, so while they kill pathogenic bacteria, they also kill healthy gut flora. However, they discovered that thuricin had a narrow spectrum of activity targeting only one gene or species, in this case C.diff.
Prevention is equally important in controlling C.diff. Dr Christian Felter, Associate Vice President (Global Medical Affairs), Sanofi Pasteur, France, described the company’s development of the investigational monoclonal antibody Cdiffense vaccine to prevent primary symptomatic CDI. It is currently in Phase 3 development and is recruiting 15,000 patients across 200 centres in 17 countries worldwide.
CDI treatment is further compounded by the continued emergence of new highly virulent strains. Dr Clifford Shone, Scientific Area Leader (Toxins), PHE, said that in severe cases, C.diff toxins A and B leak into the systemic circulation, causing widespread damage beyond the gut.
Dr Shone’s team is developing PolyCAb polycolonal antibodies for severe CDI cases. Unlike monoclonal antibodies, polyclonals are highly diverse, easier to profile, deliver broader toxin neutralisation, especially in systemic circulation pools, and are cheaper to produce. Clinical trials are slated to begin in early 2015.
With these promising approaches in development against CDI the outlook in looking considerably more optimistic than a decade ago. Panel chair Dr Albert John Misfud, Consultant Medical Microbiologist, PHE and Honorary Clinical Senior Lecturer, Queen Mary (University of London), reminded the session in his concluding speech that clinical interventions should be aligned with realistic and manageable targets. Otherwise, hospitals may become too concerned about meeting targets than diagnosing patients.