Scientists Provide Insight Into Virulent Strain of Clostridium Difficile

Scientists have characterized an emerging virulent strain of Clostridium difficile that has been associated with outbreaks of severe disease in North America and Europe. Their findings are published in this week's issue of The Lancet.

C difficile infection results in a broad spectrum of disease ranging from mild diarrhea to severe life threatening conditions. The bacterium produces two protein toxins, A and B. In 2002, hospitals in Montreal and southern Quebec, Canada, began experiencing an epidemic of severe C difficile-associated disease (CDAD), suggesting a more virulent strain of the bacterium was involved. In this study, Michel Warny of Acambis in Cambridge, Mass., and colleagues examined whether the increased virulence of this strain could be due to increased production of toxins A and B.

The investigators obtained samples from 124 patients with CDAD at the Centre Hospitalier Universitaire de Sherbrooke in Quebec. They also collected additional isolates from the United States, Canada, and the United Kingdom. Using genotyping methods, the researchers identified the virulent C. difficile strain, NAP1/027, in 67 percent of hospital-acquired CDAD cases and in 37 percentof community-acquired cases seen in Sherbrooke. In addition, they compared toxin A and B production in NAP1/027 with other contemporary non-epidemic isolates from various locations. They found that NAP1/027 could produce 16 times more toxin A and 23 times more toxin B than control strains. The study also shows that NAP1/027 carries a deletion in a gene (tcdC) involved in the control of toxin production.

Warny states, In the UK, where the number of reported cases of C difficile-associated disease doubled over three years, NAP1/027 is the cause of ongoing outbreaks in at least three hospitals where a high case-fatality ratio has been noted In the Netherlands, NAP1/027 was identified in two severe outbreaks also associated with fatalities . . . Clinicians need to be vigilant in the prevention, diagnosis and treatment of this disorder.

In an accompanying comment, Torbjorn Noren of Orebro University, Sweden, states, The possibility of CDAD epidemics calls for more comparative studies on virulent strains and antibiotic use, By highlighting the clinical aggravation of CDAD together with the spread of a virulent C difficile strain, Warny and colleagues article is of great value, supporting the new treatment strategy of neutralizing the pathogenic bowel toxin, either by a toxin-binding polymer or a vaccine.

Source: The Lancet