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Etiology of Community Acquired Clostridium
Difficile-Associated Disease

By: Shannan Sherman and Dr. Pamela Ark | Mentor: Dr. Pamela Ark

Epidemiologic Triangle


Nine studies provided information about epidemiology of infection due to C. difficile in the community and interventions to reduce transmission. The studies were conducted in a variety of settings including Sweden, the United Kingdom, Australia, Toronto, and the United States. Each study design was quantitative. Most studies were retrospective case-control studies. Of the nine studies, categories of the three different types of epidemiologic factors emerged. These factors form the epidemiologic triangle: host, agent, and environment.


In a study conducted in 1993 by Simor, Yake, and Tsimidis, three host variables were identified and associated with CDAD in a long term care facility. These variables were the presence of a nasogastric or gastrostomy tube (OR 6.5), urinary and fecal incontinence (OR 2.5), and the presence of more than three underlying diseases (OR 2.0).


Noren et al. (2004) used PCR ribotyping to type the different stool specimens obtained. There were 241 isolates of C. difficile from 241 patients and 89 isolates from 54 patients with recurrences, totaling 330 isolates that underwent PCR ribotyping. Results found 53 distinct PCR ribotypes. The patterns of PCR ribotypes of C. difficile were similar in the hospital and in the community with the exception of type SE17. Of the 53 distinct PCR ribotypes, nine compromised 67% of isolates from the hospital and 59% from the community. SE17 was the most common ribotype and accounted for 22% of hospital acquired CDAD. Of the SE17 isolates studied, 93% were identified as hospital acquired. Therefore, SE17 is predominately a nosocomial infection. A total of 208 of the 330 specimens tested were classified as hospital acquired. The remaining 122 were community acquired. Of the patients with CDAD, 68 experienced recurrences. PCR ribotyping showed that in 90% of the recurrent episodes, the isolate was the same ribotypes as the initial ribotypes. The same nine major ribotypes that caused the initial infection were associated with recurrence. Therefore, no particular C. difficile strain was more likely to cause recurrence (Noren et al., 2004).


In 1986, a study was undertaken by Riley, Wymer, Bamford and Bowman that demonstrated that several antibiotics were the central cause of CA-CDAD. The antibiotic most associated with the disease was clindamycin.

A prospective nationwide study of CDAD was carried out in Sweden during 1995. Karlström et al. found that 28% of all cases of CDAD involved no hospitalization within the preceding four weeks to diagnosis, defined as CA-CDAD (1998). Of the cases defined as community acquired, the majority were diagnosed in primary care. In addition, 88% had taken antibiotics in the previous six weeks (Karlström et al., 1998).

In 2000, Levy et al. identified two cephalosporins with increased risk for developing CDAD in the ambulatory care setting, cephalexin (OR 7.5, CI 1.8-34.7) and cefixime (OR 6.4, CI 1.2-39.0).

Dial, Delaney, Barkun, and Suissa (2005) conducted a study to determine if gastric acid suppressive drugs increased the risk for CA-CDAD. A total of 1672 patients were identified as having CDAD, and of those, 1233 (74%) infections were considered community acquired. There was a noteworthy increase in the rate of cases diagnosed as community acquired, from less than 1 per 100,000 persons in 1994, to 22 per 100,000 in 2004. Also, records showed from 1994 to 2004 a decrease in the number of antibiotic prescriptions and an increase in proton pump inhibitor prescriptions. The researchers found exposure to antibiotics as a risk factor for all cases of CDAD. In a second analysis examining only CA-CDAD, researchers found proton pump inhibitor exposure to have an adjusted rate ratio of 2.9 (CI 2.4-3.4) and H2-receptor antagonists to have a adjusted rate ratio of 2.0 (CI 1.6-2.7). Therefore, there is an increased risk for CA-CDAD with gastric acid suppressive drugs. Also, in the 90 days prior to diagnosis, only 37% of the cases had antibiotic exposure (Dial, Delaney, Barkin & Suissa, 2005).

In a study conducted by McFarland, Clarridge, Beneda, and Raugi (2007), 184 patients were diagnosed with CDAD. Twenty patients of the 184 patients (11%) had community acquired cases. More than half of the patients with CA-CDAD had no prior antibiotic exposure. Also, the patients with CA-CDAD experienced shorter duration of hospitalization and lower mortality. The majority of the patients with CDAD were treated with either metronidazole or vancomycin. Drugs considered to be high risk factors of developing CA-CDAD were clindamycin (OR 29.9) and penicillin (OR 4.1). Also, taking multiple antibiotics during the same time period increases risk for CA-CDAD (OR 1.4).

Wilcox, Mooney, Bendall, Settle, and Fawley (2008) found several risk factors for developing CA-CDAD. Exposure to antibiotics in the previous four weeks, particularly multiple agents (p < 0.001), aminopenicillins (p < 0.05), and oral cephalosporins (p < 0.05), were significantly more frequent among cases than controls. Hospitalization in the preceding six months was significantly associated with CA-CDAD (45% versus 23%; p = 0.022). Almost half the cases had not received antibiotic therapy in the month before C. difficile detection, and approximately one third experienced neither exposure to antibiotics nor recent hospitalization. Contact with infants younger than two years old was also considered a risk factor (14% versus 2%; p = 0.02).

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