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The organism known as Clostridium difficile is a gram-positive bacillus bacteria which has the ability to form spores, as well as produce a number of toxins. The toxins produced by these bacteria are presently considered to be one of the forefront causes of antibiotic-associated diarrhea (AAD).In addition, infection of this bacteria and the subsequent damage which is instigated by the organism's invasive toxins can lead to several serious gastrointestinal conditions including pseudomembranous colitis (PHAC, 2011). According to the Centre for Disease Control (2012), Clostridium difficile is proposed to be the causative of between 15 and 25% of all AAD cases in Canada. Due to its specific pathogenesis, this organism is easily spread throughout a given population, with increased risk attributed to various factors which contribute to a higher level of exposure. Given this, there are often outbreaks experienced within healthcare facilities, as well as within community settings. In addition, the organism has well known epidemiology, with certain patient attributes, exposure to high-risk environment, medical conditions and various medications contributing to an increased risk of both the asymptomatic Clostridium difficile colonization (CDC) or the symptomatic and sometimes deadly Clostridium difficile infection (CDI). Infection by Clostridium difficile can also lead to various chronic and adverse effects after the initial recovery such as recurrent infections, surgeries being required to rectify the damage which has been caused by the toxin's effect on the patient's bowels (3). As a result of this persistent organism's observable damage and tendency to spread, any sort of CDI outbreak has definite implications on the healthcare system, both from a fiscal as well as a resource and time-allocation standpoint.
Clostridium difficile (C. difficile) are gram positive, spore-forming bacillus bacteria which, as an opportunistic pathogen, inhabit the anaerobic conditions of the human gastrointestinal system. It is also the "leading cause of health care-associated diarrhea" (Bourgault, 2011). As reported in the Canadian Medical Association Journal (CMAJ), Clostridium difficile can be isolated "from the stool of 3% of healthy adults and up to 80% of healthy newborns and infants" (Kujiper, 2008). The reason that it can be so detrimental in the case of an infection is that along with a number of other virulence factors, it produces two toxins, known as toxin A and toxin B (CDC, 2012). In patients who display either a colonization or infection, the normal gastrointestinal flora is depleted due to a number of extenuating risk factors. Provided with these circumstances, the C. difficile bacteria are able to flourish and overrun the patient's bowel. The "major agressins" (Borriello, 1998) of C. difficile are undoubtedly toxins A and B, however, there are a number of other virulence factors possessed by the organism which contribute to its potential to cause harm. According to Borriello, C.difficile is influenced by its ability to adhere the intestinal wall, which may be caused by the organism's intrinsic slight positive net charge. This attracts to the "negatively charged host cells [and] may contribute to gut colonization" (Borriello, 1998). Both toxins A and B "are cytotoxic to a very large number of different cell types, both cause increased vascular permeability, and both cause haemorrhage" (Borriello, 1998). In addition, toxin A appears to cause "fluid accumulation, whereas toxin B does not" (Borriello, 1998).
Immediate clinical symptoms of C. difficile can include "fever, loss of appetite, nausea, abdominal pain and tenderness" (PHAC, 2011) as well as watery diarrhea. The diarrhea is a by-product of the toxins produced by the multiplying bacteria as they invade the mucosa of the intestines. This causes "profuse inflammatory diarrhea secondary to destruction of the lining of the colon" (4). In more severe cases, it can cause "pseudomembranous colitis, bowel perforation, sepsis, and even death" (PHAC, 2011).
There are currently several reliable, widely-used laboratory tests which are used in the diagnosis of C. difficile colonization and infection. Microbiological stool culture is the "most sensitive test available" (CDC, 2012) and is considered the confirmatory test, but it also carries the highest incidence of false-positives. This occurs when the patient is infected with a non-toxigenic strain of C. difficile. PCR assays have been developed for the gene which encodes for toxin B. In addition, antigen detection by either "latex agglutination or immunochromographic assays" (CDC, 2012) provides a fast way to detect the presence of Clostridium difficile. Again, it is non-specific for toxigenicity. Toxin testing tests for specificity to toxin B, while enzyme immunoassays can detect either toxin (CDC, 2012). As studied by Kinson in 2009, additional testing for various markers is also being investigated as a means of detecting infections. Examples of this include "fecal lactoferrin, a marker for intestinal inflammation" (Kinson, 2009) as well as glutamate dehydrogenase (GDH), which is "C. difficile-specific [â€¦] however GDH positivity is independent of toxigenicity in strains of C. difficile" (Kinson, 2009). Although its presence does confirm Clostridium difficile is present in the patient, it does not confirm that the strain present in this patient is toxigenic.
According to the Public Health Agency of Canada, mild cases of CDI can resolve with only supportive treatment such as intravenous fluids to combat dehydration (PHAC, 2011). Additionally, the Centre for Disease Control states that up to "20% of cases will resolve within two to three days of discontinuing the antibiotic to which the patient was previously exposed" (CDC, 2012). In more severe cases, "the infection can usually be treated with an appropriate course (about 10 days) of antibiotics, including metronidazole, vancomycin (administered orally), or recently approved fidaxomicin" (Aylin, 2011). If the bacteria have severely damaged sections of the bowel, it may have to be removed surgically as well (Louie, 2004).
Risk Factors for Infection
The incidence of infection by Clostridium difficile is affected by a number of risk factors, which is depicted in Figure 1 (Owens, 2008). Being hospitalized greatly increases the chances of becoming infected with C. difficile. These bacteria are shed in the feces, and are usually transmitted between patients either by healthcare workers, or by surfaces or equipment not being fully sanitized between patients (Louie, 2004). However, there has been an increasing trend of community-acquired infections as well. In a study performed at Harvard Medical School, it was found "that community-acquired Clostridium difficile infection may account for more than a third of Clostridium difficile-associated diarrhea overall (Leffler, 2012). In addition, the use of medications such as antibiotics, "particularly fluoroquinolones" (Bourgault, 2011), as well as proton pump inhibitors (used to supress production of gastric acid in gastrointestinal conditions) have been shown to increase the risk of a Clostridium difficile infection. In a study by Haider et al, it was shown that while the use of proton pump inhibitors appears to "lead to an elevated risk of developing severe CDI" (Haider, 2012), another widely used type of gastric acid suppressant medication known as histamine 2 receptor antagonist (H2RA) actually appears to decrease the risk of an infection (Haider, 2012). Gastrointestinal surgery is also a known risk factor for severe infection with Clostridium difficile (Louie, 2004). According to Public Health Ontario, infections are more likely to be considered severe in an elderly or immunocompromised patient (OAHPP, 2011). However, it has been shown that the presence of multiple medical conditions, or co-morbidity, is actually a better predictor then age as to the outcome of the infection. Severe CDI "occurs more frequently with advancing age. However, age, per se, has no effect on mortality" (Dharmarajan, 2000).
IMPLICATIONS IN PUBLIC HEALTH
It has been shown that both the financial implications, as well as the allocation of resources within the health care system produced by Clostridium difficile-associated disease (CDAD) are quite significant. Public Health Ontario stated at the time of their study in 2010, that "the cost of CDI readmissions alone is estimated to be a minimum of CAD $128,200 per year per hospital" (OAHPP, 2011). A more extensive look in to the associative costs was completed in 2008 at Washington University's School of Medicine. Dubberke studied a population of CDAD patients and proposed that a cost of $2454 was attributed to each case of CDAD, with that cost increasing to $5042 per patient if their stay exceeded 180 days of hospitalization (Dubberke, 2008). According to the study conducted in by Dr. Forster et al (2011), an infection with C. difficile extends the patient's hospital stay from an average of 8 days to an average of 34 days (Forster, 2011). This not only increases the burden on health care workers, but also utilizes time and supplies which are quite preventable.