Clostridium difficile Infection, Colorado and the Northwestern United States, 2007

To determine the incidence of Clostridium difficile infection during 2007, we examined infection in adult inpatient and outpatient members of a managed-care organization. Incidence was 14.9 C. difficile infections per 10,000 patient-years. Extrapolating this rate to US adults, we estimate that 284,875 C. difficile infections occurred during 2007.

To determine the incidence of Clostridium diffi cile infection during 2007, we examined infection in adult inpatient and outpatient members of a managed-care organization. Incidence was 14.9 C. diffi cile infections per 10,000 patient-years. Extrapolating this rate to US adults, we estimate that 284,875 C. diffi cile infections occurred during 2007.
C lostridium diffi cile infection is a major source of illness in the United States (1). Population-based estimates of its incidence tend to include only subsets of infections defi ned by the setting of C. diffi cile acquisition (2)(3)(4) or are from patient populations outside the United States (5)(6)(7)(8)(9). These studies (2)(3)(4)(5)(6)(7)(8)(9) offer useful data for control measures but do not help clinicians and policy makers understand the population-based incidence of C. diffi cile infection. To determine the incidence of C. diffi cile infection during 2007, we estimated the incidence of C. diffi cile infection among members of 2 Kaiser Permanente health plans and extrapolated our incidence estimate to the US adult population.

The Study
We identifi ed C. diffi cile infections during January 1-December 31, 2007, among Kaiser Permanente Colorado and Kaiser Permanente Northwest members >20 years of age. The health plans had a combined membership of ≈900,000 on any given day during 2007. We collected patient membership, demographic, and clinical data using electronic databases. C. diffi cile infections were identifi ed through International Classifi cation of Diseases, 9th Revision (ICD-9), code 008.45 ("Intestinal infection due to C. diffi cile") recorded during an inpatient or outpatient health care visit or a positive C. diffi cile toxin test result. To increase the likelihood that cases were symptomatic, we further required that positive toxin test results be associated with dispensation of metronidazole or vancomycin in the outpatient pharmacy in the 7 days before or after a positive test result. Specimens were reported as negative or positive on the basis of results from a Meridian Premier Toxin A/B enzyme immunoassay (Meridian Bioscience, Cincinnati, OH, USA).
A C. diffi cile infection was considered incident if the patient did not have a history of a C. diffi cile diagnosis, a positive toxin test result, or an outpatient prescription for vancomycin or metronidazole in the previous 180 days. To ensure cases were incident and to collect baseline characteristics, patients with C. diffi cile infections were required to have continuous membership and prescription drug coverage for 1 year before the date of C. diffi cile infection.
We calculated the total incidence of C. diffi cile infection as the number of incident cases among persons >20 years of age per 10,000 person-years of observation. Age-and sex-specifi c incidence rates were also calculated. A patient could have had >1 incident C. diffi cile infections if they occurred >180 days apart. Denominator data were based on duration of membership for persons >20 years of age with continuous membership and prescription drug coverage for 1 year before July 31, 2007. To project the national incidence of C. diffi cile infection, we applied pooled, agespecifi c incidence, and sex-specifi c incidence estimates to the 2007 US population. As a sensitivity analysis, we also provided the incidence projection for US whites because earlier surveys of members showed a predominantly (90%) white membership, and race data were unavailable for a substantial proportion of members.
We identifi ed 870 incident C. diffi cile infections among members >20 years of age in 2007; a total of 473 (54%) of 870 C. diffi cile infections were identifi ed among outpatients. Overall incidence was 14.9 C. diffi cile infections per 10,000 patient-years; age-specifi c incidence rates ranged from 2.4 infections per 10,000 patient-years for men 20-29 years of age to 87.1 infections per 10,000 patient-years for men >80 years of age (Table). On the basis of these age-and sex-specifi c rates, we estimated that 284,875 C. diffi cile infections occurred among the overall US population >20 years of age. We also estimated that 241,815 infections occurred among US whites (Table).

Conclusions
Our study identifi ed new infections among this managed care population in 2007 and estimated the occurrence of new infections within the US population. Our approach differed from those of previous reports that were based on individual medical institutions, hospital discharge databases, or voluntary surveillance in targeted populations and geographic areas (10)(11)(12)(13). We differentiated between incident and prevalent infections. Identifi cation of incident infections is needed to understand the causes and predictors of infection and to develop clinical interventions to prevent infection. Because we also identifi ed C. diffi cile infection among inpatients and outpatients, our estimates more fully account for total C. diffi cile infection and provide a foundation for studying the potential spread of C. diffi cile between ambulatory and hospitalized persons.
Although different objectives and methods make direct comparisons diffi cult, we found that the incidence of C. diffi cile infection among the Kaiser Permanente population studied (14.9 infections/10,000 patient-years) did not differ substantially from the 11.2 C. diffi cile-associated hospitalizations among adults per 10,000 population identifi ed in the 2005 Nationwide Inpatient Sample (14). Our estimate of 240,000-285,000 incident C. diffi cile infections in the US adult population in 2007 is comparable with the results of an extrapolation by Campbell et al., which found that on the basis of health care-facility surveillance data, 333,000 initial and 145,000 recurrent C. diffi cile infections might have occurred nationwide in 2006 (15). Although previous reports of inpatient encounters resulting from C. diffi cile infection or total C. diffi cile infections are needed to describe the impact of C. diffi cile infection on the health care system, our identifi cation of infections in inpatient and outpatient health care settings may provide a more accurate estimate of C. diffi cile infection incidence.
Many discharge databases do not include longitudinal patient identifi ers; even though these databases can identify diagnoses during hospitalizations, they cannot link hospitalizations to specifi c patients. Thus, multiple hospitalizations for recurrent or refractory C. diffi cile infection would count as multiple infections, whereas we followed-up patients over time to ensure that only incident infections were counted. Furthermore, although we relied on ICD-9 codes to identify cases among inpatients, we also used C. diffi cile toxin tests, treatment for C. diffi cile infection, and C. diffi cile-related health care encounters to identify infections in outpatients. We could have missed infections in inpatients if the ICD-9 code for C. diffi cile was absent; however, our use of toxin test results and pharmacy dispensing records likely resulted in more accurate and complete identifi cation of C. diffi cile infection among outpatients. In fact, we found that >95% of patients with positive toxin test result had a treatment-dispensing or ICD-9 code for C. diffi cile infection.
Our data might overestimate or underestimate the incidence of C. diffi cile infection or affect the interpretation of our results in 4 ways. First, our population was predominantly white. Although we are unaware of any evidence that C. diffi cile infections occur disproportionately by race or ethnicity, we projected our incidence rate to the entire and white-only US populations to acknowledge the distribution of race in the study population. Second, our insured population could be healthier than the US population. Third, Kaiser Permanante has policies and procedures that promote judicious prescription of antimicrobial drugs and effective infection control and prevention. Collectively, a healthy population, health plan policies, and clinician awareness might result in fewer C. diffi cile infections among this population than is observed in other health care settings. Fourth, toxin tests are imperfect, potentially leading to overestimation of incidence. Our study provides population-level estimates of C. diffi cile infection in inpatients and outpatients. However, more effi cient and timely methods for identifying and reporting C. diffi cile infection are needed to further improve understanding of the epidemiology of C. diffi cile infection and the interventions necessary to prevent them.