NAME: Clostridium difficile
SYNONYM OR CROSS REFERENCE: Pseudomembranous colitis, C. difficile colitis.
CHARACTERISTICS: Clostridium difficile, of the Clostridiaceae family, is motile, anaerobic, and spore-forming (forms subterminal spores) Footnote 1. Vegetative cells are rod shaped, pleomorphic, and occur in pairs or short chains Footnote 1. It is catalase and superoxide dismutase negative Footnote 1, and produces 2 types of toxins: enterotoxin A and cytotoxin B, which disrupts cytoskeleton signal transductions in the host Footnote 2.
PATHOGENICITY: C. difficile is the main cause of nosocomial antibiotic- associated diarrhea Footnote 2. Antibiotics or any other procedures that disrupt the normal intestinal microbiota can lead to the overgrowth and production of toxin by C. difficile, which leads to clinical manifestations of infectionFootnote 3. The diarrhea may range from a few days of intestinal fluid loss to life-threatening pseudomembranous colitis Footnote 2. In diarrhea without pseudomembranous colitis (PMC), feces have a foul odor and are not bloody Footnote 4. Abdominal pain with or without pyrexia may also be present along with diarrhea Footnote 4. PMC is associated with intense inflammation of the colon and formation of pseudomembranes on the intestinal mucosal surface Footnote 2. Patients with PMC also have more systemic side effects Footnote 4. Rare extracolonic manifestations of C. difficile infection include bacteremia, intra-abdominal abscess, osteomyelitis, visceral abscess, empyema, toxic megacolon, colonic perforation, and reactive arthritis Footnote 5. The production of exotoxins A and B facilitates tissue damage, which results in cell necrosis and ulceration, diarrhea and fluid secretion, and colitisFootnote 3. The strain with ribotype 027, also known as North America Pulsotype (NAP) 1, is one of the most pathogenic types of C. difficile, and the severity of this strain is based on its unusually high levels of toxin A and B production, its production of a third toxin known as the binary toxin, and its resistance to fluoroquinolone antibiotics Footnote 6Footnote 7. Another new hypervirulent C. difficile strain 078 (NAP7/8) has been associated with severe diarrhea and high mortality rates have been reported from The Netherlands Footnote 8 and other countries, including Canada Footnote 9.
EPIDEMIOLOGY: C. difficile is of worldwide prevalence as 2-5% of the normal healthy adults carry the bacteria as a part of normal gut microflora Footnote 2Footnote 4, and older people tend to have a higher percentage (10-20%) of colonization Footnote 4. The main risk factors for C. difficile infections include frail elderly, peripartum women and childrenFootnote 4Footnote 7, and antibiotic therapy. The number of severe C. difficile outbreaks associated with high mortality has increased in North America and Europe since 2000 Footnote 6, and these outbreaks are associated with strain 027. The incidence of strain 078 has increased from 3% to 13% from February 2005 to February 2008 Footnote 8.
HOST RANGE: Pigs, calves, humans Footnote 10.
INFECTIOUS DOSE: Unknown.
MODE OF TRANSMISSION: Transmission mainly occurs through the fecal-oral route, via contaminated foods, fomites, or handsFootnote 3. C. difficile overgrowth and toxin production can occur in immunocompromised patients from their natural flora. Footnote 2. Nosocomial transmission has also been reported, where infections were transmitted via hospital staff and contaminated equipment Footnote 2.
INCUBATION PERIOD: 5-10 days with a range of 1 day to weeks following antibiotic treatment for AAD (antibiotic associated diarrhea) Footnote 2.
COMMUNICABILITY: Low risk of transmission from person-to-person, although nosocomial transmission from contaminated hands, instruments such as endoscopes, and the environment have been reported Footnote 2Footnote 11. Asymptomatic patients can also act as a reservoir for the transmission of this pathogen within the hospital Footnote 11.
DRUG SUSCEPTIBILITY: Susceptible to metronidazole and oral vancomycin Footnote 2Footnote 10. C. difficile also demonstrates sensitivity to penicillins and cephalosporins in vitro, but these drugs are not used for treatment because they can be destroyed by β-lactamases/cephalosporinases produced by other intestinal bacteria and are, thus, ineffective for treatment in vivo Footnote 2.
DRUG RESISTANCE: Some rare strains resistant to metronidazole have been isolated Footnote 4. Fluoroquinolone-resistant hypervirulent strain 027 has also been isolated from North America and Europe Footnote 7.
SUSCEPTIBILITY TO DISINFECTANTS: Spores are generally resistant to disinfection. Clostridium spores are resistant to ethyl and propyl alcohols Footnote 11. High level disinfectants such as 2% glutaraldehyde can kill spores within 20 minutes Footnote 11. 8% formaldehyde and 20 ppm sodium hypochlorite are also effective against bacterial spores Footnote 12.
PHYSICAL INACTIVATION: Spores of the genus Clostridium are generally heat resistant and can withstand temperature of 116°C for 3 hours, whereas their vegetative cells can be rapidly killed by temperatures of only 55-65°C Footnote 13. Most spores can be inactivated by moist heat at 121°C for 15-30 minutes Footnote 13.
SURVEILLANCE: Monitor for symptoms.Detection of toxins in stool specimens is the Gold Standard test for diagnosis of C. difficile infection Footnote 4. Detection of toxins is done using cell culture assays, or Enzyme Immunoassay (EIA) Footnote 4. Diagnosis can also be done by culturing the bacteria on appropriate media such as egg yolk agar-based media or blood agar media Footnote 1Footnote 4. Two different approaches are commonly used for typing of C. difficile strains and include PCR-ribotyping and pulse field gel electrophoresis (PFGE) Footnote 1Footnote 4.
Note: All diagnostic methods are not necessarily available in all countries.
FIRST AID/TREATMENT: Treatment should be supportive with rebalancing of fluid levels and electrolytesFootnote 3. Antibiotic treatment should be discontinued for antibiotic associated diarrhoea (AAD) infection Footnote 2. For patients who do not respond to drug withdrawal or are present with systemic illness, oral metronidazole is used for treatment Footnote 2Footnote 4Footnote 10. Oral vancomycin has been shown to be more effective than metronidazole in treating recurrent infections Footnote 2Footnote 4Footnote 10.
PROPHYLAXIS: Antibacterial prophylaxis is not recommended for C. difficile since antibiotics can have an adverse effect on the normal gut flora Footnote 4.
LABORATORY-ACQUIRED INFECTIONS: None reported to date.
SOURCE/SPECIMENS: Human fecal and excretion samples Footnote 4, contaminated food products, and bowel luminal contents or tissue.
PRIMARY HAZARDS: Accidental ingestion of the pathogen or its toxins.
SPECIAL HAZARDS: None.
RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 15.
CONTAINMENT REQUIREMENTS: Containment level 2 facilities, equipment, and operational practices are recommended for work involving infectious or potentially infectious materials, animals, or cultures.
PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes Footnote 16.
OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities Footnote 16.
SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up Footnote 16.
DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism by autoclave, chemical disinfection, gamma irradiation, or incineration before disposing Footnote 16.
STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labeled Footnote 16.
REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.
UPDATED: December 2011
PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada
Although the information, opinions and recommendations contained in this Pathogen Safety Data sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.
Copyright © Public Health Agency of Canada, 2011 Canada