Prevention and Control of Clostridium difficile

 Clostridium difficile (C.difficile) causes a potentially life-threatening antibiotic-associated diarrhea and colitis. The organism produces a spectrum of disease, ranging from simple and self-limited diarrhea to its most advanced and characteristic form, pseudomembranous colitis. It is well recognized as the major, if not the only, important cause of infectious diarrhea that develops in patients/residents following hospitalization or admission to a long-term care facility.

The Organism

C. difficile is a spore-forming, gram-positive, strictly anaerobic bacillus that causes diarrhea and colitis in humans and in a number of animal species. The organism produces two toxins, toxin A and toxin B. Its spores can survive outside the human body for weeks to months on environmental surfaces and devices, including bedrails, commodes, thermometers, improperly sterilized endoscopes, bathing tubs, etc.

Clinical Definition of C. difficile-associated diarrhea (CDAD)

Diarrhea is defined as watery or unformed stools, occurring > 3 times a day for at least 2 days, usually associated with abdominal cramping, fever, dehydration, white blood cells in the stool, and peripheral leukocytosis.

Laboratory confirmation of a suspected case of CDAD consists of a positive result of one of the following tests:

• Endoscopy for colonic pseudomembranes
• Stool culture for C. difficile with toxin production
• Stool enzyme immunoassay for either Toxin A or Toxin B
• Stool cytotoxicity assay positive for Toxin B.

It is suggested that each facility maintain a line listing of residents with either suspected or confirmed CDAD.

Pathogenesis

Current understanding of the pathogenesis of C. difficile-associated disease (CDAD) is that C. difficile, like most other enteric pathogens, is acquired exogenously, or from outside the human body. A unique aspect of C. difficile is that the occurrence of infection depends nearly completely on prior antimicrobial therapy to disrupt the indigenous microflora of the intestine. Most often noted antimicrobials are clindamycin, cephalosporins, and penicillins, but almost every other type of antimicrobial has been implicated.

A variety of clinical outcomes ensue following acquisition of the organism. These range from asymptomatic colonic colonization, to diarrhea, to the more severe manifestations of C. difficile disease, such as pseudomembranous colitis, toxic megacolon, and colonic perforation.

Reservoir

Hospitals and long term care facilities appear to be the major reservoirs for C. difficile. The organism can be cultured from residents with and without diarrhea, from the environment of infected residents, to include bedpans, bedrails, bedside commodes, wheelchairs, etc., and from the hands of health care workers caring for these residents.

The spores of the organism can survive for weeks and months in the environment.

Residents with active diarrhea are much more infectious than those who are asymptomatic.

Transmission

Transmission of C. difficile occurs when the organism or its spores are ingested orally. This may occur because of direct contact, person to person spread on hands, or from the environment. Nosocomial transmission has been documented, and outbreaks have been reported in both hospitals and long term care facilities.

Epidemiology of CDAD

The critical epidemiologic features of CDAD in the healthcare environment include:

• Frequent antimicrobial exposure of patients
• Environmental contamination with C. difficile spores
• Contamination of the hands of personnel with C. difficile spores
• The presence of hospitalized patients colonized asymptomatically with C. difficile
• Decreased risk of CDAD in patients who are asymptomatically colonized with C. difficile

The most important risk for CDAD is antimicrobial exposure of the patient. The association of prior antimicrobial agents with C. difficile disease is nearly universal. Although CDAD is a toxin-mediated bacterial infection, almost all affected patients have recently been treated with antimicrobial agents.

The degree of environmental contamination with C. difficile is dependent upon the status of the resident in the room at the time. Contamination is highest in rooms of residents with C. difficile diarrhea, intermediate in rooms of residents who are symptomatically colonized with C. difficile, and lowest in rooms of residents who are not colonized or infected with C. difficile.

Just as the environment is contaminated, so are the hands of personnel who are in direct contact with residents and their environment. It is generally agreed that the risk of acquiring C. difficile is greater from healthcare workers than directly from the environment, although the exact mode of transmission is difficult to prove.

It has now been hypothesized that CDAD has at least a "three-hit" disease pathogenesis. Two exposures appear to be essential: first, exposure to antimicrobials, and second, exposure to toxigenic C. difficile, in that order. Clinical observations suggest that most patients do not become ill following the first two exposures, and the presence of at least one additional factor appears to be necessary for CDAD to occur. The additional factor is likely related to host susceptibility and/or immunity.

Risk Factors

Patients who are highest risk for CDAD are those who:

• Are currently taking or have recently taken antimicrobials
• Have had gastrointestinal surgery or manipulation
• Have had a long length of stay in a healthcare setting
• Have a serious underlying illness
• Are immunocompromised
• Are of advanced age

Colonization versus Disease

There are important distinctions between disease and colonization.

Symptomatic Disease

• Patient exhibits clinical symptoms, e.g., diarrhea.
• Patient usually tests positive for both the C. difficile organism and its toxin.
• Transmission of C. difficile from persons with CDAD has been well documented in hospitals and long term care facilities.

Asymptomatic Colonization

• Patient has NO symptoms, e.g., the diarrhea has stopped.
• More common than clinical disease.
• Patient is colonized with C. difficile.
• Stool samples from these patients may test positive for the organism.

Laboratory Tests for CDAD

The proper laboratory specimen for diagnosis is a single, watery, unformed or loose stool specimen (not rectal swabs). The specimen should be submitted in a clean, watertight container. Special transport media are not necessary. Testing stools of asymptomatic patients is not clinically useful and is not recommended.

Symptomatic residents, i.e., those with significant diarrhea and/or abdominal pain AND a history of antimicrobial use within the past 30 days, should have their stool tested.
The specimen should be tested for C. difficile toxins and should be cultured.

Surveillance cultures of asymptomatic residents or screening cultures of new admissions for C. difficile are not routinely indicated and should not be done.

If the stool is to be processed by the state DHMH laboratory, a C. difficile stool kit, known as a "miscellaneous" kit, should be used. Facilities should ask their local health departments for assistance in obtaining these kits.

Treatment

• In 15% to 23% of patients with symptomatic CDAD, simply stopping the offending antibiotic(s) will result in resolution of the diarrhea without any additional treatment.
• Metronidazole (Flagyl) is the preferred treatment for initial episodes of CDAD and first recurrences.
• Oral Vancomycin should be reserved for patients who do not respond to metronidazole or who have severe, life-threatening illness.

Decolonization

Treatment with metronidazole or Vancomycin of asymptomatic patients who are colonized with C. difficile in an attempt to rid the patient of the organism generally does not work and should not be attempted.

Prevention and Control

Room Placement

• Private room is recommended, especially for residents who are fecally incontinent or who cannot practice good handwashing.
• Cohort symptomatic CDAD residents only with other symptomatic CDAD residents. Because of environmental contamination, persons with CDAD should share toilets only with other CDAD residents.
• Residents with CDAD may be moved to a multiple unit room and/or cohorting may be discontinued when the diarrhea ceases. Communal activities may also resume when diarrhea ceases.

Isolation Precautions

• Contact precautions should be used for CDAD residents with diarrhea.
• Hands should be washed frequently with soap and water. Since C. difficile is a spore forming bacteria, alcohol-based hand gels and lotions are not effective in reducing the spread of the organism and are not recommended.
  
• Gloves should be worn when entering the room.
• Gowns should be worn if physical contact with the resident or the resident's environment is anticipated.
• Common use equipment such as stethoscopes should be dedicated to the infected patient and not shared between residents.
• Precautions should continue until diarrhea ceases, i.e., less than 3 stools per day.
• Long term care facilities should have some system in place for alerting healthcare workers and visitors that a resident is on contact precautions, such as labeling the chart or door of the room, without compromising that resident's privacy.

Environmental Cleaning

• The environment of a resident with CDAD should be cleaned thoroughly at least twice per day, with special attention to those items likely to be contaminated with feces, i.e., bedrails and bedside commodes.
• An EPA-approved hospital disinfectant-detergent should be used for all environmental cleaning.

Transfer of Patients

• Transfer of patients with C.difficile colonization or disease to a long term care facility must be accompanied by notice to the facility that the patient has CDAD.
• Likewise, the same notice must accompany transfer of residents with CDAD to an acute care facility from a long term care facility.
• Long term care facilities may not refuse to accept patients/residents with C. difficile colonization or disease, as long as the facility is able to place the resident according to the scheme mentioned previously.
• A patient/resident with C. difficile colonization or disease who transfers to a long term care facility does not need to have absence of diarrhea or negative stool cultures before the transfer can occur.

Rectal Thermometers

• The use of rectal thermometers is discouraged in all residents, since C. difficile has been implicated in outbreaks in hospitals and long term care facilities.
• Oral or electronic tympanic thermometers are recommended for routine use.

Outbreaks of CDAD in Long Term Care Facilities

• An outbreak of CDAD is defined as three (3) or more cases of facility acquired, symptomatic CDAD cases occurring in the same general area of the facility within a period of seven (7) days.
• Infected residents should be placed in a private room or cohorted. Once there is clinical resolution of the infection after treatment, i.e., no diarrhea, the resident(s) may be removed from precautions.
• There is no need to culture the resident(s) to remove them from precautions.
• An intense education program for staff on C. difficile and its transmission should be conducted, along with rigorous supervision of glove and gown use. If, after these procedures are done, there continue to be new cases of clinically significant CDAD, an epidemiologist from the local health department should be called in for assistance.

References

• Gerding, DN, Johnson, S, et al. C. difficile-associated diarrhea and colitis. Infection Control and Hospital Epidemiology, 1995; 16:459-477.
• Johnson, S, and Gerding, DN. Clostridium difficile-associated diarrhea. Clinical Infectious Diseases, 1998; 26 (5): 1027-1036.
• Lozniewski, A, Rabaud, C, Dotto, E, et al. Laboratory diagnosis of Clostridium difficile-associated diarrhea and colitis. Journal of Clinical Microbiology, 2001; 39 (5): 996-998.