Clostridium difficile (C. difficile) is a spore-forming, gram-positive anaerobic bacillus that produces two toxins: toxin A and toxin B. These toxins typically cause gastrointestinal disease, often with severe complications. In rare cases, C. difficile-associated disease can be fatal. Although C. difficile bacteria can be present in human intestinal tracts and cause no clinical symptoms (a condition called colonization), some individuals with C. difficile colonization are at increased risk of becoming ill. The most common risk factor for C. difficile-associated disease is exposure to antibiotics, especially those with broad-spectrum activity. Although less common, exposure to agents that suppress the immune system may also increase the risk of illness. Advanced age, severe underlying illness, gastrointestinal surgery, use of nasogastric tubes, and gastrointestinal medications (such as gastrointestinal stimulants or antacids) have also been associated with an increased risk of colonization. Most cases are acquired in hospitals or nursing homes, but an increased incidence of community–acquired C. difficile has been reported as well. Recent studies indicate that C. difficile can also be found in food products, thus raising a significant question: Can C. difficile cause foodborne illness?
Sources and Transmission
C. difficile is shed in feces. Any material, device, or surface that becomes contaminated with feces—such as toilets or bathing tubs—may serve as a reservoir for C. difficile spores. The ability of C. difficile to form spores is thought to be a key feature that enables the bacteria to persist in patients and the physical environment for long periods of time, thereby facilitating its transmission.
The spores are transferred to patients in healthcare settings mainly through the hands of healthcare personnel who have touched a contaminated surface or item. Some evidence suggests that C. difficile may be brought into healthcare environments by asymptomatic carriers—otherwise healthy individuals with no apparent symptoms. Virulent strains, which cause severe disease in populations at high risk, might also cause more frequent, severe disease in populations previously at low risk—that is, in otherwise healthy persons with little or no exposure to health-care settings or antimicrobial use. Certain emerging features of C. difficile illness, such as close-contact transmission, high recurrence rate, young patient age, bloody diarrhea, and lack of antimicrobial exposure, might indicate that the illness and its effects are changing.
C. difficile has also been linked to illness in livestock. Studies have revealed high infection rates of C. difficile among neonatal pigs. Similarly, C. difficile has been implicated as a cause of diarrhea in calves. Livestock contamination raises concerns that the bacteria may make its way into retail food products. Indeed, C. difficile has been identified in raw meat intended for pet consumption in Canada, retail ground beef in Canada, and uncooked and ready-to-eat meats in retail markets in a U.S. metropolitan area.
The detection of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain of C. difficile in retail ground beef is cause for concern. This hyper-toxin-producing strain has been a cause of serious outbreaks of healthcare-associated disease in humans in North America and Europe, and was found among a small subset of specimens from community acquired cases in Connecticut. C. difficile in retail meats may derive from a number of sources, including deposition of spores in animal muscle or other tissues, fecal or environmental contamination of carcasses, or contamination during processing or in retail meat markets. C. difficile also has been identified in ready-to-eat salads in Scotland, which may have resulted from environmental contamination or transmission by food handlers.
These studies highlight the potential for transmission through the food supply, but do not prove that transmission of C. difficile can occur from food to humans. In fact, no instances of foodborne illness associated with C. difficile have been reported to date. Further research is necessary to explore the feasibility of this route of transmission.
The incubation period from ingestion of C. difficile to the development of symptoms has not been established. Among patients taking antibiotics, symptoms can appear immediately after beginning treatment or may not develop until several weeks after it is completed.
Most often, C. difficile-associated disease includes symptoms of mild to moderate non-bloody diarrhea, sometimes accompanied by lower abdominal cramping. Systemic symptoms, such as fever, are typically absent; mild abdominal tenderness is usually the only finding on physical exam.
In more severe cases, colitis develops, with symptoms of profuse watery diarrhea and abdominal pain and distention; bloody stools are rare. Fever, nausea, and dehydration are also often present in severe cases. Furthermore, a characteristic membrane with adherent yellow plaques can be found in the colon. Patients with severe colitis are at increased risk of developing paralytic ileus (blocked colon due to lack of peristalsis―the normal rhythmic contraction of the colon muscles) and toxic megacolon (dilated colon). These conditions may lead to a decrease in diarrhea. Severe cases may also include fulminant colitis―a rapid downhill clinical course that occurs among 1% to 3% of patients. Patients may have an acute abdomen and systemic symptoms, such as fever and tachycardia, and may require surgery.
Mortality rates associated with C. difficile-related disease in the U.S. increased nearly three-fold from 1999 to 2002. A recent study, which included C. difficile-related cases where C. difficile infection was present but not listed as the underlying cause of death, demonstrated an increase in deaths from 5.7 per million population in 1999 to 23.7 per million in 2004. It is possible that the increased rates were due to the emergence of a highly virulent strain of C. difficile.
Stool cultures are the most sensitive means available to detect C. difficile, however, they are also the test most often associated with false-positive results, due to presence of non-toxigenic bacterial strains. C. difficile stool cultures are also labor intensive and require the appropriate culture environment to grow anaerobic microorganisms. Results are available within 48 to 96 hours of the test.
Antigen detection tests for C. difficile have a very fast turn around time (less than one hour); these tests detect the presence of C. difficile antigen by latex agglutination or immunochromatographic assays. Antigen tests must be combined with toxin testing to verify diagnosis. One type of antigen test, enzyme immunoassay, detects toxin A, toxin B, or both A and B. It is a same-day assay but is less sensitive than the tissue culture cytotoxicity assay. The tissue culture cytotoxicity assay detects toxin B only. This assay requires technical expertise, is costly, and requires 24 to 48 hours for a final result. It does, however, provide specific and sensitive results for C. difficile-associated disease.
It is important to note that C. difficile toxin is very unstable. The toxin degrades at room temperature and may be undetectable within two hours after collection of a stool specimen. False-negative results occur when specimens are not promptly tested or kept refrigerated until testing can be completed.
C. difficile-associated disease will resolve in one-quarter of antibiotic-related cases within two to three days of discontinuing the problematic antibiotic. The infection can usually be treated with an appropriate course (about ten days) of antibiotics, including metronidazole or vancomycin (administered orally). Following treatment, repeat testing is not recommended if the individual’s symptoms have resolved, due to the fact that many patients remain colonized. In high risk individuals, recurrence of infection or relapse may occur after treatment.
C. difficile-associated disease can be prevented in healthcare settings by using antibiotics judiciously and using contact precautions such as isolation, hand hygiene, and gloves and gowns with patients with known or suspected infection.
To ensure prevention, healthcare institutions should implement an environmental cleaning and disinfection strategy, especially for items likely to be contaminated with feces and surfaces that are touched frequently. These institutions should use an Environmental Protection Agency (EPA)-registered hypochlorite-based disinfectant for environmental surface disinfection after normal cleaning, making sure to follow the label instructions. Generic sources of hypochlorite (such as household chlorine bleach) may also be appropriately diluted and used. Alcohol-based disinfectants, however, are not effective against C. difficile and should not be used to disinfect environmental surfaces. Institutions should also follow the manufacturer’s instructions for disinfection of endoscopes and other devices. Infection control practices in long-term care and home health settings are similar to those practices recommended for traditional health-care settings.
Note: EPA-registered hospital disinfectants are recommended for general use whenever possible in patient-care areas. At present there are no EPA-registered products with specific claims for inactivating C. difficile spores, but there are a number of registered products that contain hypochlorite. If an EPA-registered proprietary hypochlorite product is used, consult the label instructions for proper and safe use conditions.
C. difficile in Ready-to-Eat Salads, Scotland
A 2008 study of ready-to-eat salads in Glasgow, Scotland found C. difficile in three (7.5%) out of forty salad samples. Samples were collected from packaged, ready-to-eat salads purchased from seven Glasgow supermarkets from May 1 through June 30, 2008. The majority (87.5%) of the salads were imported from European Union countries, and it was among those salads that the organism was found.
The specific C. difficile strains found in the salads were 001 (a common clinical isolate in Scotland) and 017 (a common European strain, negative for toxin A and positive for toxin B). None of the isolates were resistant to vancomycin or metronidazole, which is consistent with findings from other C. difficile isolates found in Scotland. Recent studies have, however, highlighted the emergence of increased resistance to metronidazole among C. difficile isolates in England.
The findings of these isolates from ready-to-eat salads highlights the potential risk associated with consuming these products, particularly since they are not cooked prior to eating. The consumption of these foods by vulnerable populations could possibly lead to C. difficile colonization and an increase in the asymptomatic C. difficile carriage rate among humans. This could result in an increase in C. difficile transmission within the community at large and in the healthcare environment. Nevertheless, as previously noted, no cases of foodborne illness linked to C. difficile have been reported.
C. difficile in Retail Meat Products, USA, 2007
In a 2007 study, packaged meats were purchased from three national-chain grocery stores in the Tucson, Arizona area. The meat products were purchased on three occasions, at one-month intervals, over a four-month period. Sampled products included both uncooked (ground beef, ground pork, ground turkey, pork sausage, and pork chorizo) and ready to eat meats (beef summer sausage, pork braunschweiger). The pork chorizo product was produced and distributed locally; all other samples were national brands. To ensure that a range of product was tested, products with different sell-by dates (a surrogate for production date) were sampled for each meat type. Samples were not, however, representative of all meat products within each grocery store.
C. difficile was found in 37 (42.0%) of 88 retail meats, including 42.4% of beef, 41.3% of pork, and 44.4% of turkey products. Ready-to-eat products were more commonly culture positive (11 out of 23, or 47.8%) than were uncooked meats (26 out of 65, or 40.0%), although the difference was not statistically significant. The highest percentages of C. difficile isolates were recovered from pork braunschweiger (62.5%) and ground beef (50.0%). No particular association of contamination was found with the meat processor, the sell-by date, the store, or the month sampled.
Approximately one-fourth of the C. difficile isolates were comprised of the 027/TT III strain, which was previously described almost exclusively in the context of the current human epidemic strain. Three-fourths of the isolates were comprised of the 078/TT V strain. Until recently, the 078 strain had been an uncommon cause of healthcare-associated C. difficile-associated disease in humans, but it is now emerging in pigs and calves with diarrhea and in persons with C. difficile-associated disease.
This study, as well as a previous study in Canada that found C. difficile in retail ground meat, raises concerns about the potential for foodborne transmission, even though they do not prove transmission of C. difficile from foods to humans. They do, however, highlight the need for further studies to characterize the risks posed by this organism in the human food supply.
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Sunenshine RH, McDonald LC. Clostridium difficile-associated disease: new challenges from an established pathogen. Cleve Clin J Med. 2006;73(2):187-97. See also the Centers for Disease Control and Prevention website on C. difficile infections: http://www.cdc.gov/ncidod/dhqp/id_Cdiff.html