Frequently Asked Questions about Clostridium difficile for Healthcare Providers

Clostridium difficile is a spore-forming, Gram-positive anaerobic bacillus that produces two exotoxins: toxin A and toxin B. It is a common cause of antibiotic-associated diarrhea (AAD). It accounts for 15-25% of all episodes of AAD.

• pseudomembranous colitis (PMC)
• toxic megacolon
• perforations of the colon
• sepsis
• death (rarely)

Clinical symptoms include:

• watery diarrhea
• fever
• loss of appetite
• nausea
• abdominal pain/tendernes

The risk for disease increases in patients with:

• antibiotic exposure
• proton pump inhibitors
• gastrointestinal surgery/manipulation
• long length of stay in healthcare settings
• a serious underlying illness
• immunocompromising conditions
• advanced age

Clostridium difficile colonization

• patient exhibits NO clinical symptoms
• patient tests positive for Clostridium difficile organism and/or its toxin
• more common than Clostridium difficile infection

Clostridium difficile infection

• patient exhibits clinical symptoms
• patient tests positive for the Clostridium difficile organism and/or its toxin

• Stool culture for Clostridium difficile: While this is the most sensitive test available, it is the one most often associated with false-positive results due to presence nontoxigenic Clostridium difficile  strains. However, this can be overcome by testing isolates for toxin production (i.e. so called “toxigenic culture”). Nonetheless, stool cultures for Clostridium difficile  are labor intensive, require an appropriate culture environment to grow anaerobic microorganisms, and have a relatively slow turn-around time (i.e. results available in 48-96 hours) making them overall less clinically useful. Results of toxigenic cultures do serve as a gold-standard against which other test modalities are compared in clinical trials of performance.
• Molecular tests: FDA-approved PCR assays, which test for the gene encoding toxin B, are highly sensitive and specific for the presence of a toxin-producing Clostridium difficile organism. 
• Antigen detection for Clostridium difficile: These are rapid tests (<1 hr) that detect the presence of Clostridium difficile  antigen by latex agglutination or immunochromatographic assays. Because results of antigen testing alone are non-specific, antigen assays have been employed in combination with tests for toxin detection, PCR, or toxigenic culture in two-step testing algorithms.
• Toxin testing for Clostridium difficile:
  • Tissue culture cytotoxicity assay detects toxin B only. This assay requires technical expertise to perform, is costly, and requires 24-48 hr for a final result. It does provide specific and sensitive results for Clostridium difficile infection. While it served as a historical gold standard for diagnosing clinical significant disease caused by Clostridium difficile, it is recognized as less sensitive than PCR or toxigenic culture for detecting the organism in patients with diarrhea.
  • Enzyme immunoassay detects toxin A, toxin B, or both A and B. Due to concerns overtoxin A-negative, B-positive strains causing disease, most laboratories employ a toxin B-only or A and B assay. Because these are same-day assays that are relatively inexpensive and easy to perform, they are popular with clinical laboratories. However, there are increasing concerns about their relative insensitivity (less than tissue culture cytotoxicity and much less than PCR or toxigenic culture).
• Clostridium difficile toxin is very unstable. The toxin degrades at room temperature and may be undetectable within 2 hours after collection of a stool specimen. False-negative results occur when specimens are not promptly tested or kept refrigerated until testing can be done.

Clostridium difficile is shed in feces. Any surface, device, or material (e.g., commodes, bathing tubs, and electronic rectal thermometers) that becomes contaminated with feces may serve as a reservoir for the Clostridium difficile spores. Clostridium difficile spores are transferred to patients mainly via the hands of healthcare personnel who have touched a contaminated surface or item.

In about 20% of patients, Clostridium difficile infection will resolve within 2-3 days of discontinuing the antibiotic to which the patient was previously exposed. The infection can usually be treated with an appropriate course (about 10 days) of antibiotics, including metronidazole, vancomycin (administered orally), or recently approved fidaxomicin. After treatment, repeat Clostridium difficile testing is not recommended if the patients’ symptoms have resolved, as patients may remain colonized.

• Use antibiotics judiciously
• Use Contact Precautions: for patients with known or suspected Clostridium difficile  infection:
  • Place these patients in private rooms.  If private rooms are not available, these patients can be placed in rooms (cohorted) with other patients with Clostridium difficile infection.
  • Use gloves when entering patients’ rooms and during patient care.
  • Perform Hand Hygiene after removing gloves.
    • Because alcohol does not kill Clostridium difficile spores, use of soap and water is more efficacious than alcohol-based hand rubs. However, early experimental data suggest that, even using soap and water, the removal of C. difficile spores is more challenging than the removal or inactivation of other common pathogens.
    • Preventing contamination of the hands via glove use remains the cornerstone for preventing Clostridium difficile  transmission via the hands of healthcare workers; any theoretical benefit from instituting soap and water must be balanced against the potential for decreased compliance resulting from a more complex hand hygiene message.
    • If your institution experiences an outbreak, consider using only soap and water for hand hygiene when caring for patients with Clostridium difficile infection.
  • Use gowns when entering patients’ rooms and during patient care.
  • Dedicate or perform cleaning of any shared medical equipment.
  • Continue these precautions until diarrhea ceases.
    • Because Clostridium difficile-infected patients continue to shed organism for a number of days following cessation of diarrhea, some institutions routinely continue isolation for either several days beyond symptom resolution or until discharge, depending upon the type of setting and average length of stay.
• Implement an environmental cleaning and disinfection strategy:
  • Ensure adequate cleaning and disinfection of environmental surfaces and reusable devices, especially items likely to be contaminated with feces and surfaces that are touched frequently.
  • Consider using an Environmental Protection Agency (EPA)-registered disinfectant with a sporicidal claim for environmental surface disinfection after cleaning in accordance with label instructions; generic sources of hypochlorite (e.g., household chlorine bleach) also may be appropriately diluted and used. (Note: Standard EPA-registered hospital disinfectants are not effective against Clostridium difficile  spores .) Hypochlorite-based disinfectants may be most effective in preventing Clostridium difficile  transmission in units with high endemic rates of Clostridium difficile infection.
  • Follow the manufacturer’s instructions for disinfection of endoscopes and other devices.
• Recommended infection control practices in long term care and home health settings are similar to those practices taken in traditional health-care settings.

Surfaces should be kept clean, and body substance spills should be managed promptly as outlined in CDC’s “Guidelines for Environmental Infection Control in Health-Care Facilities.” [PDF 1.4 MB] Routine cleaning should be performed prior to disinfection. EPA-registered disinfectants with a sporicidal claim have been used with success for environmental surface disinfection in those patient-care areas where surveillance and epidemiology indicate ongoing transmission of Clostridium difficile.
Note: EPA-registered disinfectants are recommended for use in patient-care areas. When choosing a disinfectant, check product labels for inactivation claims, indications for use, and instructions.

Over the past several years nationwide, states have reported increased rates of C. difficile infection, noting more severe disease and an associated increase in mortality. C. diff infection remains a disease mostly associated with healthcare (at least 80%) Patients most at risk remain the elderly, especially those using antibiotics. Although the elderly are still most affected, more disease has been reported in traditionally ‘low risk’ persons such as healthy persons in the community, and peripartum women. These changes may be largely due to the new emergence of the current epidemic strain of C. difficile, known by its names assigned by various typing schemes as restriction enzyme analysis type BI, North American Pulsed Field type 1 (NAP1), or PCR ribotype 027.  BI/NAP1/027  has spread widely after first being found responsible for outbreaks in Pittsburgh (2000), Atlanta (2001-2), and Montreal (2003). This strain appears more virulent possibly due to its increased production of toxins A and B and its production of an additional toxin known as binary toxin, as well as other factors still under study. In addition to being more virulent, it is more resistant to a commonly-used class of antimicrobials known as the fluoroquinolones. Additional information about this strain and how it has changed the face of C. diff infection see Bench-to-bedside review: Clostridium difficile colitis.

Like other strains of C. difficile, BI/NAP1/027 can be detected in the stool of infected patients by using laboratory tests that are commonly available in most hospitals. However, none of the FDA-approved tests differentiate between the various strains of C. difficile. Fortunately, because the control measures for outbreaks of any strain of C. difficile are similar, identification of the specific strain is not imperative for controlling outbreaks.

The usual treatment for C. difficile infection includes, if possible, stopping antibiotics being given for other purposes and/or treatment with metronidazole or vancomycin. In order to reduce selective pressure for vancomycin resistance in enterococci, current guidelines recommend the first-line use of metronidazole over vancomycin.

Recent reports suggest that BI/NAP1/027 may not respond as well to treatment with metronidazole despite the absence of laboratory evidence of metronidazole resistance. Evidence suggests that more severe disease should be treated with vancomycin, over metronidazole.

Increased fluoroquinolone resistance does not affect the management of infections caused by this strain. Fluoroquinolones have never been recommended for treatment of C. difficile infection and susceptibility testing is performed only as a part of an epidemiological investigation. However, resistance to fluoroquinolones may provide the new strain with an advantage over susceptible strains to spread within healthcare facilities where these antibiotics are commonly used.

Healthcare facilities should monitor the number of C. difficile infections and, especially if rates at the facility increase, the severity of disease and patient outcomes. If an increase in rates or severity is observed, healthcare facilities should reassess compliance with core recommended practices as outlined in the Options for Evaluation of Enviromental Cleaning for known cases of C. diff infection including the following:

If compliance appears high to core recommendations, consideration should be made to implement supplemental recommendations as described in the toolkit.. If assistance is needed with these measures, additional help should be sought from local or state health departments and/or local infection control experts.

The Centers for Disease Control and Prevention also has General Information about Clostridium difficile.