Clostridium Difficile Comes of Age

Abstract

Clostridium difficile, dubbed the CD superbug by the tabloid press, is the most frequent cause of nosocomial diarrhea worldwide. C. difficile associated disease (CDAD) ranges from mild to chronic diarrhea and sometimes life-threatening disease of the gut termed pseudomembranous colitis. CDAD occurs when the bacteria that normally reside in the gut and protect it from harmful infection are killed by antibiotic treatment. This leaves the gut available for colonization by C. difficile once the antibiotic treatment finishes. The population at risk is substantial, including not only patients on antimicrobial therapy, but also the immunocompromised and the elderly. Since broad-spectrum antibiotics exacerbate the condition, treatment is difficult, especially for these susceptible groups, and the relapse rate is high (≤55%). Beyond the morbidity and mortality caused, CDAD is a substantial economic problem that can lead to patient isolation, ward closures and in extreme cases, hospital closure. More disturbingly, the reported incidence of CDAD has increased significantly in the last decade and a new hypervirulent strain is causing outbreaks of increased severity in North America and Europe [1]. The origin of this strain, termed the NAP1/027 hypervirulent strain, is uncertain, although it has been proposed that increased use of fluoroquinolones may provide a selective advantage for this epidemic strain [1]. In the UK, CDAD is a notifiable disease and for patients over 65 years of age alone, the reported incidence in 2006 was 51,690 cases. This represents a 17.2% increase on the previous year’s figures and a 30-fold increase in the number of reported cases 10 years ago. The numbers of reported C. difficile cases are now three-times those for the notorious methicillinresistant Staphylococcus aureus (MRSA) pathogen and the mortality rates for C. difficile last year far exceeded those for MRSA infection. Despite the importance of C. difficile, the pathogen does not have the profile of other pathogens and has yet to seep into the public consciousness. Given the continued use of broad-spectrum antibiotics, the aging population, increasing rates of hospitalization and the emergence of the hypervirulent strain, the incidence of CDAD is likely to continue to rise. Clearly this is alarming – but what is being done to stem the flood of C. difficile infection? The answer is, very little. Attempts to improve hospital hygiene are valiant, but as with MRSA this is not the long-term solution. A programme of research dedicated to understanding what makes the C. difficile microorganism tick at the molecular level is required. Through information derived from such studies the rational design of long-term interventions can be implemented to reduce the burden of disease (this is also true for other hospital superbugs). It is scandalous how very little government funds go into basic research on hospital superbugs – the public would be shocked [2]. The Healthcare Commission in the UK, under the direction of the Secretary of State for Health, published a report in July 2006 on a large outbreak of C. difficile infection in the Stoke Mandeville Hospital, Buckinghamshire, UK, which occurred in 2004/2005. The report was highly critical of control measures used and highlighted the unacceptably high number of deaths in the outbreak. This may be true, but blaming hygiene measures and hospital staff is a convenient excuse and does not address the underlying problem of the emergence of the hypervirulent strains.