infection has been traditionally thought of as a hospital-acquired or healthcare-associated infection. However, data from this population-based cohort suggests that a substantial fraction of CDI cases was acquired in the community. We also found a significant increase in the incidence of CDI in both inpatients and outpatients over the study period and, as seen previously, this increase in CDI incidence was most striking in the elderly. Most importantly, our results demonstrate that CDI impacts populations previously thought to be at low-risk, including young adults and children, and those who lack the traditional risk factors of hospitalization or antibiotic exposure. In this cohort, community-acquired CDI was common in younger patients (61% of younger patients acquired infection in the community), the majority of patients were females, and many of them (22%) were not exposed to antibiotics in the 90-day period before acquiring CDI. A recent epidemiological study showed a similar gender distribution and 98.3% of community-acquired CDI cases occurred in patients less than 65 years of age (15
). In a case-control study of community-acquired CDI, antibiotic exposure was not present in 52% of CDI patients in the 4 week time period prior to onset (13
). In our study, there were no differences in acid-suppression medication use in the community- and hospital-acquired CDI patients. Other studies of community-acquired CDI have reported that a similar lack of antibiotic and proton-pump inhibitor exposure (14
). These observations suggest that there may be additional or different risk factors for community-acquired CDI.
The difference in age based on mode of acquisition was expected (4
), as hospitalized patients tend to be older than community dwellers in general. However, the community-acquired CDI cohort also was more likely to be female than the hospital-acquired cohort. The reason for the difference in gender is not clear. We considered that it might be related to differential exposure to antibiotics, with females being more likely to seek medical attention (and therefore be exposed to antibiotics) in the outpatient setting than men, while in hospitalized patients, exposure to antibiotics is less likely to be related to gender. However, we found no significant association between gender and antibiotic use, and the effect of gender on acquisition mode was not modified by antibiotic use.
In our cohort, there were no differences in severity or recurrence rates between community-acquired and hospital-acquired CDI on initial analysis. However, the lack of difference in severity should be interpreted with caution. A significant proportion of patients did not have the markers of severity (serum creatinine and white blood cell count) measured. Assuming that these patients were not so severely ill as to warrant a clinician to order these tests, we reanalyzed the data considering patients in whom these markers were not available as having mild-moderate infection. This secondary analysis suggested that community acquired infection was significantly less likely to be severe than hospital-acquired infection.
As reported previously, we also found that CDI was more common and more severe in the elderly and that the increase in incidence over the study period was most striking in the oldest subset of our cohort. The majority of the elderly cases were hospital-acquired, and were more likely to have severe or severe complicated infection or required hospitalization in the community-acquired elderly patients.
There has been a significant increase in severe cases, colectomies, and death related to CDI in recent reports (7
). In one of these studies, severe disease was present in 12% of patients, but was 2.7 fold higher in the elderly (22
). The rates for colectomy and mortality secondary to CDI has increased from 2.5-fold to 5-fold in different studies from 1993–2004 (23
). Using the recent consensus definitions (20
), severe disease occurred in 36% of our cohort and severe complicated occurred in 7%, with no significant change over the study period. As reported previously, both occurred in a significantly higher proportion of the elderly in our study.
Our findings are consistent with several other reports which show an increase in the incidence and severity of CDI world-wide since the mid to late 1990s (3
). For example, there was a large outbreak in Quebec, with a four-fold increase in CDI, increasing severity and, unlike in our study, a 2.3-fold increased risk of recurrence (47% compared to 21%) over a 13-year period, with a mortality of 6.9% (5
). The Canadian Nosocomial Infection Surveillance Program Study estimated the incidence rate for CDI in adult patients admitted to hospitals as 4.6 cases per 1000 patient admissions and 65 per 100,000 patient-days (31
) which was 4-fold higher than the overall crude incidence rate observed in our cohort. However, these studies did not include community-dwelling subjects with CDI, which would lead to an over-estimate of overall incidence since the incidence in community-dwellers is lower than in hospitalized subjects. In addition, we chose to exclude 30 patients with probable CDI due to lack of a confirmatory stool assay.
In large retrospective studies in the United States, the incidence of hospital-acquired CDI increased by 2 to 2.5 fold from the late 1990s to the early 2000s, especially in the elderly (7
). The rate of hospitalization due to CDI increased by about 23% per year from 2000 to 2005 (25
), but from 2005 through 2006, the rate increased by only 6.7% (28
). In contrast, in our cohort, the rate of hospitalization for community-acquired CDI did not vary significantly over the study period.
The majority of CDI epidemiological data is derived from hospital-based reports and administrative databases, such as the US National inpatient sample data and the national mortality data for CDI surveillance (24
). There have been relatively few studies describing the epidemiology and characteristics of community-acquired CDI (4
). Most of the CDI studies use hospital discharge data and laboratory data as the primary source of case identification. The use of hospital discharge data has the potential to miss community-acquired cases, and laboratory databases have the potential to include false positive CDI as these patients might be colonized with Clostridium difficile
but not have symptomatic infection.
The major strength of our study is that data has been collected over a period of 15 years from a stable population. Collecting data from a population-based cohort allowed us to study and compare the epidemiology of CDI in both hospital- and community-acquired cohorts. The resources of the Rochester Epidemiology Project allowed the identification of all cases of CDI in county residents and access to all the medical record information for each case. However, we were unable to analyze of trends in the use of Clostridium difficile stool testing in county residents over the study period due to unavailability of this data, thus limiting our ability to assess for diagnostic detection bias. Other limitations of this study include some missing data, such as laboratory tests used for defining severe CDI, and lack of information on Clostridium difficile strain, which was not being collected in our laboratory during the time period of this study. Finally, during the course of this study, the diagnostic test for CDI transitioned from stool cytotoxicity assay to enzyme immunoassay (EIA). Since EIA has a lower sensitivity than the cytotoxicity assay, it is likely that this change in diagnostic test underestimated the true increase in incidence that we saw over the study period.