Clostridium difficile Infection

1. Basic Facts About Clostridium difficile and Clostridium difficile infection (CDI)

Clostridium difficile (C. difficile) is an anaerobic, gram-positive bacterium. It can exist in two forms: a dormant spore that has a tough protein coat, and a vegetative form that results from spore germination. Because of the anaerobic nature of the bacteria, the dormant spore is the infectious and transmissible form.1 C. difficile was first detected in the lower intestinal tract of newborns in 1935, but it is not considered to be a normal commensal bacterium of the gut.2 It was not until 1978 that it was understood to cause the disease commonly known as Clostridium difficile infection (CDI). C. difficile is a common bacteria and has been isolated from soil, houses, shops and healthcare facilities.3, 4

How Is CDI Caused?

C. difficile causes pseudomembranous colitis, a severe inflammatory infection of the colon that is commonly known as CDI. In general, two conditions — colonization with C. difficile and exposure to antibiotics — are necessary prerequisites for infection to develop. In healthy individuals, C. difficile spores may colonize the gut, coexisting with a diverse range of bacteria — known as commensals — that make up the microbiota. The diverse commensal bacteria form a mucus layer on the epithelial cells of the intestinal tract.

However, following antibiotic treatment, the normal gut microbiota is disrupted and many commensal bacteria are killed. In this situation, microorganisms such as C. difficile may not be affected by the antibiotic and can proliferate. As a result, C. difficile spores can attach to the epithelial wall of the small intestine, germinate into the vegetative state, and reproduce. This causes the release of two exotoxins — toxin A and toxin B — which attack the epithelial cells and cause mucosal damage.5 Studies suggest that toxin B is responsible for C. difficile virulence.6, 7

The susceptibility of the patient or the virulence of the C. difficile strain may also play a role in determining whether the infection develops. Some people who experience colonization and exposure to antibiotics may become only asymptomatically colonized.8

While most antibiotics are suspected of being a trigger for the development of CDI, the risk appears to be higher for specific classes of antibiotics such as cephalosporins, fluoroquinolones and clindamycin. In recent outbreaks, the fluoroquinolone class of antibiotics has been implicated.9, 10

Who Is Affected by CDI?

CDI can affect people of all ages. However, the risk of developing CDI is greatest in patients over 65, those with chronic health conditions and comorbidities such as diabetes, those undergoing gastrointestinal surgery, those who are immunocompromised and those who have a history of prior antibiotic use.11 Additionally, those who are subject to long stays in healthcare settings such as hospitals, nursing homes and long-term care facilities are also at increased risk.

CDI Symptoms

Depending on the virulence of the infecting C. difficile strain, the toxins can cause illness ranging from mild diarrhea to pseudomembranous colitis. In all cases, the major symptom of CDI is diarrhea. Mild cases may experience only this symptom, while severe cases can include severe abdominal cramping, blood or pus in the stool, nausea, a swollen abdomen, kidney failure and an increased white blood cell count.12 A significant proportion of patients require a colectomy — removal of the colon. Severe infection can lead to sepsis and death.

How Is CDI Treated?

CDI is treated by the administration of antibiotics that can kill C. difficile bacteria. For milder cases of CDI, metronidazole is the most commonly prescribed antibiotic. For more severe cases, vancomycin or fidaxomicin administered orally will most likely be prescribed. A course of treatment usually lasts for a minimum of 10 days. More recently, fecal transplants — transplants of stool from healthy people — have been used to treat CDI with some success, although the long-term safety has not been established.12

What Is Recurrent CDI?

For a significant proportion of CDI patients, recurrent disease remains a risk. Recurrent disease occurs in around 20% of patients, can occur as little as one to two weeks after resolution of the initial infection, and may occur multiple times. The first recurrence is usually treated with the same antibiotics that were used to treat the initial infection. Multiple recurrent infections are usually treated with vancomycin or fidaxomicin.13

2. The Burden of Clostridium difficile Infection

CDI is one of the most prevalent healthcare-associated infections in the United States. According to a 2015 study based on surveillance carried out by the Centers for Disease Control and Prevention (CDC), nearly 500,000 Americans suffer from CDI annually, with one in five having recurrent disease. CDI is responsible for over 23,000 deaths annually and over $4.6 billion in treatment costs.13

Between 2001 and 2010, the incidence of CDI nearly doubled among adults hospitalized in the United States.14 Since 2010, the mortality rate has begun to decline, although infection rates continue to rise.

3. Transmission of Clostridium difficile

There are two main reservoirs of C. difficile: infected or colonized patients, and inanimate surfaces and objects in the healthcare environment. Transmission occurs through the fecal-oral route. As C. difficile spores are found in the gastrointestinal tract and because diarrhea is associated with CDI, the spores are shed in the stool of CDI patients and those who are asymptomatically colonized with C. difficile. Shed spores can contaminate healthcare workers’ hands and shared equipment such as thermometers, infusion pumps, mobile devices and commodes, and are then easily transmitted between patients by ingestion of spores after a contaminated surface is touched.15, 16 Studies on the survival of C. difficile on hard surfaces such as those found in the healthcare environment have shown that while the vegetative form dies within 24 hours, C. difficile spores can persist for months.17 This long survival period of the spores increases the risk of transmission from a contaminated surface that has not been properly cleaned and disinfected.

The CDC describes three categories of CDI acquisition: CDI is considered to be healthcare facility onset if a stool sample is positive more than three days after hospital admission or in a resident of a long-term care facility. CDI is considered to be community-onset, healthcare facility associated when a positive stool is collected in an outpatient setting, or within three days after hospital admission in a person with a documented overnight stay in a healthcare facility. Community-associated CDI occurs when the positive stool is collected in an outpatient setting or within three days in a person with no documented overnight stay in a healthcare facility.18 While hospitals are recognized as a major source of the infection, the incidence of community-associated CDI is increasing.

4. Preventing C. difficile Transmission: The Importance of Surface Disinfection and Hand Hygiene

The CDC emphasizes a number of actions that healthcare providers can take to prevent CDI:19

  • Prescribe and use antibiotics carefully.
  • Use proper diagnostic tests for accurate results.
  • Rapidly identify and isolate patients with CDI.
  • Practice contact precautions such as the wearing of gloves and gowns when treating C. difficile patients.
  • Practice hand hygiene using soap and water. Alcohol-based hand sanitizers do not inactivate C. difficile.
  • Clean and disinfect the rooms of CDI patients daily and on discharge with an EPA-registered disinfectant with claims against C. difficile spores.
  • When a C. difficile patient transfers, notify the new facility of the infection.

The cleaning and disinfection of surfaces, and hand hygiene, are critical activities that can help to prevent the transmission of C. difficile spores from patient to patient.

Surface Disinfection

C. difficile spores are resistant to many common disinfectants, so an EPA-registered disinfectant with a claim to inactivate C. difficile spores should be used. Rooms of CDI patients should be cleaned and disinfected daily, with particular attention paid to high-touch areas such as bed rails, bedside furniture, commodes, light switches and doorknobs, mobile devices, and medical equipment and monitors. Particular attention should also be paid to items shared between patients.

Hand Hygiene

Appropriate hand hygiene techniques should be practiced by patients, healthcare staff and visitors. Hands should be washed with soap and water for at least 30 seconds, followed by thorough drying with paper towels. Alcohol-based hand sanitizers do not inactivate C. difficile and should not be used when soap and water are available.

How Family Members and Visitors Can Help

As part of an education program, family and visitors should be educated about how they can help prevent C. difficile transmission. This includes being provided with information on the disease and transmission, the correct way to wash hands, how to identify visitors who may be at greater risk for acquiring C. difficile and the steps they can take once patients are discharged, such as cleaning and disinfecting homes, not sharing towels or hygiene products, and best practices for laundering.

5. CloroxPro Disinfectants with EPA-Approved Claims Against C. difficile

CloroxPro offers a range of bleach-based disinfectants that have an EPA-registered claim against C. difficile on hard, nonporous surfaces.

ProductProduct detailsC. difficile
contact time
Clorox Healthcare® Fuzion® Cleaner DisinfectantReady-to-use spray; 0.39% sodium hypochlorite2 min
Clorox Healthcare® Bleach Germicidal Disinfectants WipesReady-to-use wipes; 0.55% sodium hypochlorite3 min
Clorox Healthcare® Bleach Germicidal CleanerReady-to-use cleaner-disinfectant
in a spray bottle or pull-top; 0.65%
sodium hypochlorite
2 min
Dispatch® Hospital Cleaner Disinfectant Towels with BleachReady-to-use wipes; 0.65% sodium hypochlorite3 min
Clorox® Germicidal Bleach8.25% sodium hypochlorite; dilute 1:14 to
make a 0.59% solution
5 min

References

1. Paredes-Sabja D, Shen A, Sorg JA. Clostridium difficile spore biology: sporulation, germination, and spore structural proteins. Trends Microbiol. 2014;22(7): 406–416.
2. Leffler DA, Lamont JT. Clostridium difficile Infection. N Engl J Med 2015;372:1539-1548
3. Alam MJ, Walk ST, Endres BT, et al. Community environmental contamination of toxigenic Clostridium difficileOpen Forum Infect Dis 2017 Feb 10;4(1).
4. Alam MJ, Anu A, Walk ST, Garey KW. Investigation of potentially pathogenic Clostridium difficile contamination in household environs. Anaerobe 2014;27:31-3.
5. Reeves AE, Theriot CM, Bergin IL, et al. The interplay between microbiome dynamics and pathogen dynamics in a murine model of Clostridium difficile Infection. Gut Microbes 2011;2:145-158.
6. Lyras D, O’Connor JR, Howarth PM, et al. Toxin B is essential for virulence of Clostridium difficileNature 2009;458:1176-1179.
7. Sambol SP, Tang JK, Merrigan MM, Johnson S, Gerding DN. Infection of hamsters with epidemiologically important strains of Clostridium difficileJ Infect Dis 2001;183:1760-1766.
8. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis 1998;26:1027-1034.
9. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol 2005;26:273-280.
10. Gaynes R, Rimland D, Killum E, et al. Outbreak of Clostridium difficile infection in a long-term care facility: Association with gatifloxacin use. Clin Infect Dis 2004;38:640-645
11. Mayo Clinic. C. difficile infection. https://www.mayoclinic.org/diseases-conditions/c-difficile/symptoms-causes/syc-20351691. Accessed December 15, 2017.
12. Centers for Disease Control and Prevention. Clostridium difficile infection information for patients. https://www.cdc.gov/hai/organisms/cdiff/cdiff-patient.html. Accessed December 15, 2017.
13. Lessa, FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile Infection in the United States. N Engl J Med 2015; 372:825–834.
14. Reveles, KR, Lee, GC, Boyd, NK, Frei, CR. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J.Infect Control 2014;42:1028–1032.
15. Shaughnessy MK, Micielli RL, Depestel DD, et al. Evaluation of hospital room assignment and acquisition of Clostridium difficile infection. Infect Control Hosp Epidemiol 2011;32:201-206.
16. McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial acquisition of Clostridium difficile infection. N Engl J Med 1989;320:204-210.
17. Kramer, A.; Schwebke, I.; Kampf, G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis 2006(6):130.
18. Centers for Disease Control and Prevention. Clostridium difficile infection (CDI) tracking.  https://www.cdc.gov/hai/eip/clostridium-difficile.html. Accessed December 15, 2017.
19. Centers for Disease Control and Prevention. Frequently Asked Questions about Clostridium difficile for Healthcare Providers.  https://www.cdc.gov/hai/organisms/cdiff/cdiff_faqs_hcp.html. Accessed December 15, 2017.

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