Decline in C. Difficile may be due to Decreased Antibiotic Exposure Interview with:
David W. Eyre, B.M., B.Ch.
Nuffield Department of Clinical Medicine
University of Oxford
National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
John Radcliffe Hospital What are the main findings of this study?

Dr. Eyre: All cases of Clostridium difficile in Oxfordshire were studied over 3 years. Isolates were characterized by whole genome sequencing and the data was linked to hospital databases allowing epidemiological relationships between patients at the level of the hospital ward, hospital specialty, and post code to be identified. For comparison, similar information was also available for all other patients with and without diarrhea.  Preliminary work on the genetic diversity of Clostridium difficile within individuals and between individuals within discrete outbreaks allowed reliable interpretation of transmission events using genomic data.

This allowed a complete reconstruction of the pattern of transmission between affected cases in Oxfordshire to be made.

The findings were:
1. Unexpectedly few cases (13%) appear to be acquired from direct ward based contact with other symptomatic cases (these have previously been thought to be the main source of infections, and the focus of prevention efforts). Another 6% were associated with other hospital contact and 3% had plausible community contacts.

2. In 13% of cases potential donors were identified gnomically but no contact, within hospitals or the community, were identified. This suggests that the existence of other modes of transmission of Clostridium difficile.

3. The sources of Clostridium difficile infections were highly genetically diverse, with 45% of cases having a genetically distinct origin – suggesting a diverse reservoir of disease, not previously appreciated

4. During the 3 years of the study the rate of Clostridium difficile in Oxfordshire fell.  Any improvement in infection control techniques would be expected to reduce the incidence of cases caused by within hospital transmission. Surprisingly, similar rates of fall occurred in both in secondary cases (considered to be acquired from hospital associated symptomatic cases) and for primary cases (cases not associated with transmission from symptomatic cases). What should patients and clinicians take away from your report?

Dr. Eyre: This suggests that the decline in Clostridium difficile was due to factors that prevent the transition from simple exposure and asymptomatic carriage to overt disease. The main factor known to determine this factor is antibiotic exposure, particularly quinolones and cephalosporins: the use of these antibiotics fell significantly in the UK during the 3 years of the study. Hence, it is likely that the fall in incidence in Clostridium difficile was likely to be due to restriction of use of antibiotics rather than an improvement in infection control.
Therefore new ways to combat infection, including a greater focus on antibiotic use and identification of the reservoirs of infection are needed What further research do you recommend as a result of of this study?

Dr. Eyre: Identification of the reservoirs of infection, not currently well understood the extent to which each contribute to transmission and which are important in human disease


Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing

David W. Eyre, B.M., B.Ch., Madeleine L. Cule, Ph.D., Daniel J. Wilson, D.Phil., David Griffiths, B.Sc., Alison Vaughan, B.Sc., Lily O’Connor, B.Sc., Camilla L.C. Ip, Ph.D., Tanya Golubchik, Ph.D., Elizabeth M. Batty, Ph.D., John M. Finney, B.Sc., David H. Wyllie, Ph.D., Xavier Didelot, D.Phil., Paolo Piazza, Ph.D., Rory Bowden, Ph.D., Kate E. Dingle, Ph.D., Rosalind M. Harding, Ph.D., Derrick W. Crook, M.B., B.Ch., Mark H. Wilcox, M.D., Tim E.A. Peto, D.Phil., and A. Sarah Walker, Ph.D.

N Engl J Med 2013; 369:1195-1205
September 26, 2013
DOI: 10.1056/NEJMoa1216064


Last Updated on September 26, 2013 by Marie Benz MD FAAD