By Kelly A. Reynolds, MSPH, PhD
First associated with disease in 1978, C. difficile is not a new pathogen. It is the most frequent cause of nosocomial acquired diarrhea in developed nations, resulting in more than 300,000 infections in U.S. hospitals per year.
If you haven’t yet heard of Clostridium difficile (C. diffifile), you soon will. This spore-forming bacteria is gaining notoriety and increasingly responsible for serious infections leading to illness and death in epidemic proportions. More information is becoming available regarding environmental reservoirs of C. difficile and water has emerged as a common reservoir.
A dangerous bacterium
First associated with disease in 1978, C. difficile is not a new pathogen. It is the most frequent cause of nosocomial acquired diarrhea in developed nations, resulting in more than 300,000 infections in US hospitals per year.
The disease is most often nosocomial (acquired during a hospital stay) but can also be community-acquired. Studies show that nearly half of patients diagnosed with significant C. difficile infections are immunocompromised. Recent exposure to antibiotics is a major risk factor, reported in more than 90 percent of patients.
Infections from C. difficile are typically mild and self-limiting but others lead to severe diarrhea, colitis and death. In fact, one to two percent of cases requiring treatment in a hospital develop into fulminant infection with 20 percent requiring colectomy.. Mortality rates among those requiring surgery are a dramatic 35 to 80 percent.
Only recently has C. difficile been a notifiable disease and thus the incidence data is limited in many regions. Wales reported a high incidence of 1.6/1000 persons, resulting in over 87,000 cases per year. Patients with C. difficile colonization in long-term care facilities ranges from four to 20 percent during non-outbreak periods.
Even in the general, healthy adult population, three percent are colonized. Interestingly, neonates are also highly colonized- with reports ranging from five to 70 percent prevalence- but they are much less likely than adults to progress to disease, possibly due to a lack of developed receptors for one of the bacteria’s toxins. 
Risk factors for C. difficile disease include those who: 1) use of antibiotic treatments-particularly broad spectrum medications; 2) are over 65 years of age (the elderly are 10 times more susceptible); 3) are recently or currently hospitalized; 4) live in an extended care facility; 5) are severely immunocompromised, 6) have had abdominal surgery or invasive gastrointestinal procedures; 7) have inflammatory bowel disease or colon disease; and 8) have a previous C. difficile infection (source: Mayo Clinic [March 2009]. www.mayoclinic.com/health/c-difficile/ds00736).
Reinfection or relapse is very common. Between 12 to 25 percent of patients experience a second round of C. difficile infection within two months of a previous infection. For some, reoccurrence is frequently repeated.
Death from C. difficile is relatively rare but since 2000, numerous reports of such deaths have surfaced. Mortality rates in Quebec are now estimated at nearly seven percent. Incidence rates have also doubled from 2000 to 2003 in the US, Canada and Europe.
Canada reported an increase of 35 cases per 100,000 persons in 1992 with an increase to 160 per 100,000 in 2003. The most dramatic increases are among adults over the age of 65 where the incident rate jumped to 900 per 100,000 persons.
Sudden and dramatic increases in incidence and mortality rates suggested the possibility of a new, more aggressive, strain developing in the population. In 2005, a new strain of C. difficile was indeed identified.
The new strain was found to produce increased amounts of toxins A and B (the main virulence factors of C. difficile) and also produces an additional toxin, binary toxin, whose role in disease progression is presently unclear. Patients with this strain of the bacterium were twice as likely to progress to severe disease.
A study in New Jersey hospitals in 2004 found a two-fold increase in C. difficile disease, a seven-fold increase in complications and a 12-fold increase in outbreaks since the discovery of the newer, more virulent strain. In 2005, the US Centers for Disease Control and Prevention (CDC) recommended that in-patient healthcare facilities track the incidence of C. difficile-associated disease and patient outcomes and recognize the role of the new strain in the recent epidemic. Today, screening for C. difficile is standard for patients with diarrhea.
In order for C. difficile to establish in the colon, the normal microbial flora must be disrupted, as can occur with the use of antibiotics and also the bacterium has to be introduced to the gut via ingestion. While toxins A and B are known to cause inflammation and mucosal damage leading to diarrhea or colitis, it is unknown why some cases progress to severe disease while others do not.
Reports of severe infection and death are among both immunocompromised and otherwise healthy individuals. Researchers are testing opposing theories on colonization and whether it may lead to disease or possibly be protective by allowing the body to build up immune factors to fight off future infections.
Exposure to C. difficile is via the fecal-oral route. Infected persons shed the bacteria in their feces and thus, any environment subject to fecal contamination can serve as a route of transmission, including contaminated food, water, surfaces or hands. Animal feces, including domestic food animals and pets, have also tested positive for the bacteria. Persons may ingest live, growing (vegetative) forms of the bacteria or the hardy dormant spore form that subsequently germinates in the gut.
Little is known about the role of the environment, including contaminated drinking water, on the transmission and persistence of C. difficile. One study conducted in Wales found the bacteria was highly prevalent in source and recreational waters, tap water and swimming pools, among other environments.
A total of 2,580 environmental samples were collected with an overall rate of 7.1 percent positive sites. River waters yielded the most positive results with 87.5 percent (14/16 samples) contaminated with C. difficile. Other positive sites included swimming pools (50 percent, 4/8 samples), sea water (44 percent, 7/15 samples), soil (21 percent, 22/104 samples) and tap water mains (5.5 percent, 1/18 samples.
These same researchers isolated C. difficile from 20 percent of surfaces in hospitals and 2.2 percent of surfaces in private residences. Survey of 524 pets and farm animals showed that about one percent of farm animals, 10 percent of dogs and two percent of cat feces were also positive.
In addition, 2.4 percent of 300 raw vegetable samples were positive. C. difficile appears to be widespread in the environment but particularly in water. Interestingly, the organism was never detected in the gut of fish (0/107 samples).
C. difficile should be suspected in any adult with antimicrobial-associated diarrhea occurring within several months of treatment. Although infection is primarily associated with antibiotic therapies, children and adults with no known risk factors have been impacted as well. A fatal case in an otherwise healthy 37-year-old male routinely treated for bronchitis exemplifies the unpredictable nature of the disease and importance of preventing exposure and improving diagnosis that can lead to early treatment.
Symptoms from C. difficile proliferation may occur immediately after beginning antibiotic treatment or several weeks after treatment has stopped. Treatment for C. difficile can be effective and usually involves stopping the initial antibiotic use and applying treatment specifically directed toward C. difficile, such as Metronidazole in mild cases and Vancomycin for severe infections.
One study found that 97 percent (n=189) responded to initial treatment.5 Mild disease can progress very quickly to severe disease and thus rapid and complete treatment procedures are warranted. Fear over the development of antibiotic resistance in C. difficile are valid as recent data indicates a decreasing effectiveness of antibiotics in some surveys.
Treatment of asymptomatic colonization is not recommended. The use of probiotic agents and fecal enemas have been explored (i.e., replacing the good bacteria in the gut) but a definitive study of effectiveness of such treatments has not been published.
The spread of C. difficile is well documented in the literature and infection control procedures of isolating colonized patients, improved handwashing and diligent surface disinfection help to reduce the spread of infection and outbreaks. Unfortunately, the popular alcohol hand gels are not effective against C. difficile and traditional handwashing techniques using soap and water is necessary.
The highly resistant spore form of the bacteria can persist for weeks on surfaces even after use of routine disinfectants. 5 Bleach-based products, however, have been effective at reducing surface contamination and outbreaks in hospitals.
Many studies are needed to evaluate the efficacy of various disinfectants against C. difficile, possible transmission routes of the organism and various risk factors related to disease. While sodium hypochlorite is an effective surface disinfectant, little information is available looking at the need or efficacy of treatment in drinking water sources.
As with similar pathogens, the best prevention will likely be a multi-barrier approach with combined efforts of reducing exposure, avoiding antibiotics, improving hygiene and rapid utilization of effective post-infection treatments. Unnecessary antimicrobial therapy can increase the risk of C. difficile and thus elimination of this practice is further warranted. According to the CDC, of all the preventative measures recommended to reduce C. difficile infections, the most effective has been to restrict the use of indiscriminate antibiotics.
- Byrn et al., Predictors of mortality after colectomy for fulminant Clostridium difficile colitis. Archives of Surgery. 143(2)150-154.
- Eglow, R., Pothoulakis, C., Itzkowitz S., et al., 1992. Diminished Clostridium difficile toxin. A sensitivity in newborn rabbit ileum is associated with decreased toxin A receptor. Journal of Clinical Investigation. 90:822-829.
- Gravel, D. and Miller, M. 2007. Clostridium difficile associated diarrhea in acute-care hospitals participating in CNISP: November 1, 2004-April 30, 2005. Canadian Nosocomial Infection Surveillance Program.
- McDonald, L.C., Kilgore, G.E., Thompson, A., et al., 2005. An epidemic, toxin gene-variant strain of Clostridium difficile. New England Journal of Medicine. 353: 2433-2441.
- Sunenshine, R. and McDonald, L.C. 2006. Clostridium difficile-associated disease: New challenges from an established pathogen. Cleveland Clinical Journal of Medicine. 73(2):187-197.
- Al Saif, N. and Brazier, J.S. 1996. The distribution of Clostridium difficile in the environment of South Wales. Journal of Medical Microbiology. 45(2):133-137.
About the author
Dr. Kelly A. Reynolds is an associate professor at the University of Arizona College of Public Health. She holds a Master of Science degree in public health (MSPH) from the University of South Florida and a doctorate in microbiology from the University of Arizona. Reynolds has been a member of the WC&P Technical Review Committee since 1997. She can be reached via email at [email protected].