The bacterium Clostridium difficile has been in the news regularly over the last few years, usually in relation to outbreaks of infection in hospitals and care homes for the elderly. It is the subject of much concern because it can cause potentially serious intestinal infections that are difficult to treat successfully. Controlling Cl. difficile effectively also seems to be quite problematic for healthcare institutions.

Until recently there has been little attention given to Cl. difficile as a possible foodborne pathogen, but some recent research findings have suggested that food may have a role in its transmission. The following Briefing Note examines what is known about this potentially serious pathogen, looks at the evidence for Cl. difficile as an emerging cause of foodborne illness and considers whether food producers need to take any action.

Clostridium difficile as a human pathogen

Like other clostridia, Cl. difficile is a Gram-positive, anaerobic, rod-shaped bacterium that is able to produce endospores that are quite resistant to heat, drying and chemical sanitisers. It can be found in the soil, water and in the faeces and intestinal tracts of animals and humans. First isolated about 70 years ago, it has been known as an occasional cause of intestinal infection in animals and humans since 1978. However, more recently Cl. difficile has become a major cause of hospital-acquired gastrointestinal disease in the developed world, producing infections under the general heading of Clostridium difficile Associated Diarrhoea (CCAD). CCAD may manifest itself as a range of conditions, ranging from mild diarrhoea to potentially life threatening pseudo-membranous colitis, a serious inflammation of the large intestine. Death rates have been reported to vary from 6% to 30% when colitis is present.

Like its well known food-poisoning relative, Clostridium perfringens, Cl. difficile causes illness by the production of exotoxins in the gut. Toxin-producing strains of Cl. difficile can produce two major toxins, A and B, although some strains only produce toxin B. Toxin A is an enterotoxin that causes fluid secretion and inflammation, while toxin B is a more potent cytotoxin, causing tissue damage. A few strains can also produce a binary toxin (CDT), which appears to be involved in pathogenicity, though its true significance is still uncertain.

The main risk factor for Cl. difficile infection is treatment with broad-spectrum antibiotics, especially by mouth. The antibiotics usually associated with Cl. difficile infection are clindamycin, the penicillins and the cephalosporins, but recently some outbreaks have been linked to treatment with fluoroquinolones - previously thought to be low risk. These antibiotics disrupt the normal microbial populations in the gut and it is thought that this disruption allows Cl. difficile spores to germinate and produce exotoxins, giving rise to CCAD cases. Increasing age is also a risk factor, with older patients being much more vulnerable to infection.

Transmission has generally been considered to be by the faecal-oral route, with poor hygiene in hospital wards and care facilities, coupled with the widespread use of antibiotics, being the main factors in the development of CCAD outbreaks. Up to 70% of newborn babies have been found to carry Cl. difficile in their guts without apparent symptoms, but a much lower proportion of healthy adults (~3%) are thought to be carriers.

CCAD is quite a common disease, especially in hospitals. For example, in the UK, about 40,000 cases a year are reported in people over the age of 65, with a probable further 10,000 cases in younger people. Similar incidences of CCAD probably exist in other countries. The vast majority of these cases are in hospital patients, but it is likely that CCAD is under-reported in the wider community and until recently there has been very little information available on incidence outside healthcare facilities.

Why is the problem getting worse?

Since about 2000 the severity of hospital outbreaks of CCAD appears to have been increasing, and more cases of serious illness, more complications and higher death rates have been reported. For example, in 2003, CCAD outbreaks were reported in hospitals in Canada with a mortality rate of 13.8%, whereas recorded death rates from CCAD in the period from 1991-2 were only 4.8%. Similar increases have been reported in hospital outbreaks in the USA, the UK and the Netherlands.

The reasons for this are still under investigation and may include changes in the use of antibiotics, changes in antibiotic-resistance patterns of some strains, and the emergence of more virulent strains of Cl. difficile. Much attention has focused on a strain known as ribotype 027. This produces all three toxins and has a mutation that allows it to produce larger quantities of toxin - 16 times more toxin A and 23 times more toxin B - and this may in part account for the increased virulence. This strain is also reported to be more resistant to fluoroquinolone antibiotics.

Cl. difficile ribotype 027 seems to be spreading rapidly around the world, with serious outbreaks having been recorded in North America, Japan and Europe. Ribotype 027 has now been reported from at least 15 countries. About 28% of all isolates of Cl. difficile from hospital patients in England are now reported to be ribotype 027. However, experts are not unanimous in blaming this strain for the increasing severity of CCAD outbreaks. A recently published epidemiological study from the UK found no evidence that outbreaks caused by ribotype 027 were any more severe than those caused by other ribotypes.

There is also some evidence that more cases of CCAD are being reported in individuals with none of the known risk factors. For example, a study in the state of Connecticut in the USA found an incidence of 7.6 cases per 100,000 in generally healthy people in the community during 2005. Many of these people were young, had not spent time in hospital and had no history of antibiotic treatment. Similar observations have been made in recent community studies in Philadelphia and in the UK. Diagnoses of CCAD by doctors in the UK in the community rose from less than 1 case per 100,000 to 22 cases per 100,000 in the ten year period between 1994 and 2004 according to one recent report, although this increase has yet to be properly verified. In the USA it has been estimated that about 20,000 Cl. difficile infections occur each year in the community. This suggests that there may be other risk factors for infection that are as yet unknown.

Food as a source of Clostridium difficile

The main reason for the recent interest in Cl. difficile as a potential cause of foodborne disease is some recent research conducted at the University of Guelph, in Canada. These studies found that Cl. difficile strains known to infect humans - including ribotype 027 - could be found in a significant number (11% approx) of calves from dairy farms. Toxins A and B were also found in the faeces of calves on more than half the farms visited.

The researchers then went on to look at samples of ground meat on retail sale and found that 12 out of 60 samples were positive for Cl. difficile. Eight of these isolates were classified as 'toxinotype III' (similar in some respects to ribotype 027) and two were identified as human pathogens. Since that study was published, other researchers have looked at meat on sale to the public and found similar results. For example, testing of samples of ground beef in France showed that Cl. difficile was present in almost 5% of the samples.

As a common soil organism, Cl. difficile can also be isolated from plant material and vegetables, although little is known about the strains present, or their pathogenicity.

Should food producers be concerned?

Since Cl. difficile produces heat resistant spores like those of Clostridium perfringens, it is likely that some spores will survive normal cooking times and temperatures if they are present in ground beef products, such as burgers. Theoretically, spores might also be present in some other food products, such as ready-to-eat cooked meats, chilled ready meals and salads, although further surveys are needed to confirm this. Therefore it is quite probable that some viable spores of Cl. difficile strains pathogenic to humans could occasionally be ingested with food.

Whether this means that infection can be foodborne is another matter entirely. The spores of Cl. difficile do not produce toxin or illness unless they are able to germinate in the gut and information is still largely lacking on many of the factors that cause this to happen. As yet there is no evidence for any cases of CCAD that can be conclusively classified as foodborne. Nevertheless, foodborne transmission appears to be a possibility and certainly needs to be investigated. Until some firm evidence one way or the other is forthcoming, food producers can only continue to apply the same food safety and hygiene practices that are already in place to control known foodborne pathogens.

The best advice at present is simply to keep a watching brief.

Further Information

Publications

Kuijper et al.
Emergence of Clostridium difficile-associated disease in North America and Europe
Clinical Microbiology and Infection, 2006, 12(Suppl. 6), 2-18.
http://ecdc.europa.eu/Health_topics/Clostridium_difficile/pdf/C-difficile.pdf

Rodriguez-Palacios et al.
Clostridium difficile in retail ground meat, Canada
Emerging Infectious Diseases, 2007, 13(3)
http://www.cdc.gov/eid/content/13/3/485.htm

On the web

ECDC information on Cl. difficile
http://ecdc.europa.eu/Health_topics/Clostridium_difficile/Clostridium_difficile.html

CDC information on Cl. difficile
http://www.cdc.gov/ncidod/dhqp/id_cdiff.html