Case-control study of antibiotic use and subsequent Clostridium difficile-associated diarrhea in hospitalized patients.

OBJECTIVE: To determine which antibiotics increase or decrease the risk of Clostridium difficile-associated diarrhea (CDAD). DESIGN: Retrospective case-control study. SETTING: Nonprofit, integrated healthcare delivery system in Northern California. PATIENTS: Study participants included patients with cases of hospital-acquired CDAD that occurred during the period from 1999 through 2005 (n=1,142) and control patients (n= 3,351) matched for facility, calendar quarter during which hospitalization occurred, diagnosis related group for the index hospitalization, and length of hospital stay. All case and control patients had received antibiotics in the 60 days before the index date. For each antibiotic, the risk of CDAD was examined in relation to whether the patient received the antibiotic, after adjustment for use of other antibiotics, demographic characteristics, selected health conditions, and use of healthcare services. RESULTS: The following antibiotics were associated with a significantly increased risk of acquiring CDAD: imipenem-cilastin (odds ratio [OR], 2.77), clindamycin (OR, 2.31), cefuroxime (OR, 2.16), moxifloxacin (OR, 1.88), ceftazidime (OR, 1.82), cefpodoxime (OR, 1.58), ceftizoxime (OR, 1.57), and ceftriaxone (OR, 1.49). Metronidazole and doxycycline were associated with a significantly reduced risk of CDAD (OR for metronidazole, 0.67; OR for doxycycline, 0.41). Other factors associated with an increased risk of CDAD were older age, longer hospital stays, use of proton pump inhibitors, prior gastrointestinal disease, and prior infection (not including C. difficile infection.) CONCLUSIONS: Some antibiotics appear to increase the risk of acquiring CDAD, notably clindamycin, third-generation cephalosporins, and carbapenems, whereas metronidazole and doxycycline appear to be protective, compared with other antibiotics.     

Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005

Clostridium difficile is a spore-forming, gram-positive bacillus that produces exotoxins that are pathogenic to humans. C. difficile-associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis and death. Antimicrobial use is the primary risk factor for development of CDAD because it disrupts normal bowel flora and promotes C. difficile overgrowth. C. difficile typically has affected older or severely ill patients who are hospital inpatients or residents of long-term-care facilities. Recently, however, both the frequency and severity of health-care-associated CDAD has increased; from 2000 to 2001, the rate of U.S. hospital discharge diagnoses of CDAD increased by 26%. One possible explanation for these increases is the emergence of a previously uncommon strain of C. difficile responsible for severe hospital outbreaks. Although individual cases of CDAD are not nationally reportable, in 2005, the Pennsylvania Department of Health (PADOH) and CDC received several case reports of serious CDAD in otherwise healthy patients with minimal or no exposure to a health-care setting. An investigation was initiated by the Philadelphia Department of Public Health (PDPH), PADOH, and CDC to determine the scope of the problem and explore a possible change in CDAD epidemiology. This report summarizes the results of the investigation in Pennsylvania and three other states, which indicated the presence of severe CDAD in healthy persons living in the community and peripartum women, two populations previously thought to be at low risk. The findings underscore the importance of judicious antimicrobial use, the need for community clinicians to maintain a higher index of suspicion for CDAD, and the need for surveillance to better understand the changing epidemiology of CDAD.     

Antimicrobial drugs and community-acquired Clostridium difficile-associated disease, UK

In a population-based case-control study of community acquired Clostridium difficile-associated disease (CDAD), we matched 1,233 cases to 12,330 controls. CDAD risk increased 3-fold with use of any antimicrobial agent and 6-fold with use of fluoroquinolones. Prior use of antimicrobial agents did not affect risk for CDAD after 6 months.     

Clostridium difficile-associated disease in Oregon: increasing incidence and hospital-level risk factors.

BACKGROUND: The incidence of Clostridium difficile-associated disease (CDAD) appears to be increasing. Population-based estimates of disease have been limited, and analyses of hospital-level risk factors for CDAD are lacking. We sought to determine the incidence and trends of CDAD in Oregon and to identify hospital-level factors associated with increases in disease. METHODS: We analyzed hospital discharge data to calculate the incidence and to describe trends of CDAD in Oregon from 1995 through 2002. We administered questionnaires to hospital laboratory directors, infection control practitioners, and pharmacists to determine the status of laboratory, infection control, and pharmacy policies over time. RESULTS: The overall incidence of CDAD in Oregon was 3.5 case patients per 10,000 residents in 2002. Incidence increased from 1.4 to 3.3 cases per 1,000 hospital discharges from 1995 to 2002. Rates of disease increased most in hospitals with licensed bed capacity of more than 250 beds and more than 5 intensive care unit beds. Few laboratories, infection control practitioners, and pharmacists were able to identify changes in specific policies over the study period. CONCLUSIONS: This is the first study to determine a statewide population-based incidence of CDAD. Incidence of CDAD in Oregon has more than doubled over the past decade; larger hospitals experienced the greatest increase in disease rates. We did not identify hospital-level policies that could explain the increase. A study of patients with CDAD at the hospitals with the largest increases is underway to further identify risk factors.     

Fluoroquinolone use and Clostridium difficile-associated diarrhea

We performed a case-control study to evaluate the association between antibiotic use and Clostridium difficile-associated diarrhea (CDAD), matching for admission unit and time at risk for CDAD. A multivariable regression model showed that treatment with fluoroquinolones (odds ratio 12.7; 95% confidence interval 2.6 to 61.6) was the strongest risk factor for CDAD.     

Quinolone use as a risk factor for nosocomial Clostridium difficile-associated diarrhea.

OBJECTIVE: To determine modifiable risk factors for nosocomial Clostridium difficile-associated diarrhea (CDAD). DESIGN: Case-control study. SETTING: 300-bed tertiary-care hospital. PARTICIPANTS: Hospital inpatients present during the 3-month study period. METHODS: Case-patients identified with nosocomial CDAD over the study period were compared to two sets of control patients: inpatients matched by age, gender, and date of admission; and inpatients matched by duration of hospital stay. Variables including demographic data, comorbid illnesses, antibiotic exposure, and use of gastrointestinal medications were assessed for case- and control-patients. Conditional logistic regression was performed to identify risk factors for nosocomial CDAD. RESULTS: 27 case-patients were identified and were compared to the two sets of controls (1:1 match for each comparison set). For the first set of controls, use of ciprofloxacin (odds ratio [OR], 5.5; 95% confidence interval [CI 95], 1.2-24.8; P=.03) was the only variable that remained significant in the multivariable model. For the second set of controls, prior exposure to cephalosporins (OR, 6.7; CI 95, 1.3-33.7; P=.02) and to ciprofloxacin (OR, 9.5; CI 95, 1.01-88.4; P=.05) were kept in the final model. CONCLUSIONS: Along with cephalosporins, prior quinolone use predisposed hospitalized patients to nosocomial CDAD. Quinolones should be used judiciously in acute-care hospitals, particularly in those where CDAD is endemic.     

难辨梭菌相关性疾病临床危险因素的研究

目的 分析难辨梭菌相关性疾病(CDAD)的临床治疗和用药危险因素,为遏止CDAD发病上升趋势,降低医疗成本提供依据.方法 对45例CDAD患者与85例非CDAD患者病例进行回顾性对照研究;比较两组患者在治疗药物、措施:胃肠道手术、灌肠术,实验室化验指标:白细胞、白蛋白的差异;各研究变量先进行单因素分析,有统计学差异的纳入logistic回归模型进行多因素分析.结果 回归模型显示,头孢菌素类:OR=3.321,95％CI:1.54～7.14,β=1.647、喹诺酮类OR=2.438,95％CI:1.15～5.15,β=1.255、糖肽类OR=0.232,95％CI:0.06～0.83,β=-2.130,抗菌药物的使用与CDAD存在显著性相关性(P＜0.05).结论 头孢菌素类、喹诺酮类抗菌药物的不合理使用,是导致CDAD发生的主要危险因素,糖肽类药物使用可以作为预防CDAD发生的保护性因素.     

Clostridium difficile among hospitalized patients receiving antibiotics: a case-control study.

OBJECTIVES: Clostridium difficile is the most common cause of infectious nosocomial diarrhea and can be found in up to 30% of asymptomatic hospitalized patients. Our primary aim was to compare the clinical characteristics of hospitalized patients who received antibiotics and developed C. difficile-associated diarrhea (CDAD) with those of hospitalized patients who received antibiotics and did not develop the disease. DESIGN: Case-control study comprising inpatients at a single institution. PATIENTS: Case-patients were defined as patients who had diarrhea and tested positive for C. difficile. Control-patients (matched 4:1 to case-patients) were defined as patients who received antibiotics for at least 5 days and did not develop CDAD. RESULTS: On univariate analysis, nine variables were associated with CDAD. Only three of the variables, need for intensive care, length of stay, and macrolide antibiotic use, were found to be significant (P < .05) on logistic regression analysis. The odds ratios for status as a CDAD case were 3.68 (CI95, 1.44 to 9.40) for stay in the intensive care unit and 1.03 (CI95, 1.02 to 1.05) for each day of hospital stay. Receipt of macrolide antibiotics reduced risk significantly; the odds ratio was 0.23 (CI95, 0.19 to 0.87). CONCLUSIONS: We identified need for intensive care and length of stay as important risk factors for the development of CDAD. We also identified macrolide antibiotic use as protective against its development. Patients receiving intensive care may represent a population to study for targeted prophylaxis.     

Clostridium difficile-associated disease in patients in a small rural hospital.

OBJECTIVE: To determine the risk factors for Clostridium difficile-associated disease (CDAD) in a 25-bed rural hospital and to compare antimicrobial use ratios at the study hospital with those at a large academic medical center. DESIGN: Case-control study. SETTING: A 25-bed rural hospital in Iowa during the period from August 2002 through January 2005. PATIENTS: A total of 17 case patients with CDAD and 34 control patients matched for age (ie, within 10 years of the case patient's age), sex, and admission date (ie, within 2 weeks of the case patient's admission date). METHODS: Retrospective medical record review was performed to obtain data on antimicrobial exposures during the 6 weeks before hospital admission for both case and control patients. Exact conditional logistic regression was used for univariable and multivariable analyses. Antimicrobial use ratios were calculated to compare the rates of antimicrobial use for case and control patients at the study hospital with the rates for patients evaluated in a study of CDAD at a nearly 700-bed teaching hospital. RESULTS: Case patients had a larger cumulative number of days of antimicrobial use (P=.004), and they received a larger total number of antimicrobial agents during hospitalization (P=.001). Antimicrobial use ratios were higher for both case and control patients at the smaller hospital, compared with the larger hospital. CONCLUSIONS: CDAD at a small rural hospital was not associated with exposure to the antimicrobial classes that are typically associated with CDAD, but was instead related to the total number of antimicrobials used to treat patients. The rate of antimicrobial use for case and control patients was about 40% higher at the small rural hospital, compared with the corresponding rates at a large academic medical center.     

Costs of nosocomial Clostridium difficile-associated diarrhoea

Nosocomial Clostridium difficile-associated disease (CDAD) is a common infection in hospitals. A matched case-control study was carried out to determine hospital-wide excess costs due to CDAD. Cases were assessed by prospective hospital-wide surveillance in a tertiary care university hospital in 2006. Nosocomial cases of CDAD (>72h after admission) were matched to control patients without CDAD in a ratio 1:3 using the same diagnosis-related group in the same year, for a hospital stay at least as long as the time of risk of the CDAD cases before infection and a Charlson comorbidity index +/-1. Data on overall costs per case were provided by the finance department. Matching was possible for 45 nosocomial CDAD cases. The difference in the length of stay showed that CDAD cases stayed significantly longer (median 7 days; P=0.006) than their matched controls. The average cost per CDAD patient was euro33,840. The difference in the cost per patient showed that the cost for CDAD patients was significantly more than for their matched controls (median euro7,147; 95% confidence interval: 4,067-9,276). Nosocomial CDAD is associated with high costs for healthcare systems. Clinicians should be aware of the financial impact of this disease and the application of appropriate infection control measures is recommended to reduce spread.     

Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure.

OBJECTIVE: To evaluate the epidemiology, outcomes, and importance of Clostridium difficile colonization pressure (CCP) as a risk factor for C. difficile-associated disease (CDAD) acquisition in intensive care unit (ICU) patients. DESIGN: Secondary analysis of data from a 30-month retrospective cohort study. SETTING: A 19-bed medical ICU in a midwestern tertiary care referral center. PATIENTS: Consecutive sample of adult patients with a length of stay of 24 hours or more between July 1, 1997, and December 31, 1999. RESULTS: Seventy-six (4%) of 1,872 patients were identified with CDAD; 40 (53%) acquired CDAD in the ICU, for an incidence of 3.2 cases per 1,000 patient-days. Antimicrobial therapy, enteral feeding, mechanical ventilation, vancomycin-resistant enterococci (VRE) colonization or infection, and CCP (5.5 vs 2.0 CDAD case-days of exposure for patients with acquired CDAD vs no CDAD; P=.001) were associated with CDAD acquisition in the univariate analysis. Only VRE colonization or infection (45% of patients with acquired CDAD vs 16% of patients without CDAD; adjusted odds ratio, 2.76 [95% confidence interval, 1.36-5.59]) and a CCP of more than 30 case-days of exposure (20% with acquired CDAD vs 2% with no CDAD; adjusted odds ratio, 3.77 [95% confidence interval, 1.14-12.49]) remained statistically significant in the multivariable analysis. Lengths of stay (6.1 vs 3.0 days; P<.001 by univariate analysis) and ICU costs ($11,353 vs $6,028; P<.001 by univariate analysis) were higher for patients with any CDAD than for patients with no CDAD. CONCLUSIONS: In this nonoutbreak setting, the CCP was an independent risk factor for acquisition of CDAD in the ICU at the upper range of exposure duration. Having CDAD in the ICU was a marker of excess healthcare use.     

Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is an important infection in hospital settings. Its impact on outpatient care has not been well defined. OBJECTIVE: To examine risk factors of ambulatory cancer patients with CDAD. DESIGN: Case-control study. SETTING: Memorial Sloan-Kettering Cancer Center, a tertiary-care hospital. METHODS: Cases of CDAD among oncology outpatients from January 1999 through December 2000 were'identified via positive C. difficile toxin assay results on stool specimens sent from clinics or the emergency department. A 1:3 matched case-control study examined exposures associated with CDAD. RESULTS: Forty-eight episodes of CDAD were identified in cancer outpatients. The mean age was 51 years; 44% were female. Forty-one (85%) had received antibiotics within 60 days of diagnosis, completing courses a median of 16.5 days prior to diagnosis. Case-patients received longer courses of first-generation cephalosporins (4.8 vs 3.2 days; P = .03) and fluoroquinolones (23.6 vs 8 days; P < .01) than did control-patients. Those receiving clindamycin were 3.9-fold more likely to develop CDAD (P < .01). For each additional day of clindamycin or third-generation cephalosporin exposure, patients were 1.29- and 1.26-fold more likely to develop CDAD (P < .01 and .04, respectively). The 38 CDAD patients hospitalized during the risk period (79.2%) spent more time as inpatients than did control-patients (19.3 vs 9.7 days; P < .001). CONCLUSIONS: Antibiotic use, especially with cephalosporins and clindamycin, and prolonged hospitalization contributed to the development of CDAD. Outpatient CDAD appears to be most strongly related to inpatient exposures; reasons for the delayed development of symptoms are unknown.     

Albumin, length of stay, and proton pump inhibitors: key factors in Clostridium difficile-associated disease in nursing home patients

OBJECTIVES: To identify risk factors for Clostridium difficile-associated disease (CDAD) in nursing home patients. DESIGN: Retrospective chart reviews. SETTING: Long-term care facility with 347 beds and an additional 180 sub-acute care beds, adjacent to an academic tertiary care hospital center. PARTICIPANTS: Twenty-five patients had documented diagnosis of CDAD. Eighty-four percent were female, 76% white, 16% black, 4% Asian, and 4% Hispanic. Age ranged between 60 and 97 years (mean: 82.2 years). The control group had 28 patients, 68% were female, 89% white, and 11% black. Age ranged between 61 and 101 years (mean: 82.3 years). MEASUREMENTS: Length of stay at the facility, initial presenting symptoms, white blood cell count at the time of diagnosis, serum albumin level prior to the start of antibiotics, body mass index calculated from weight and height, presence or absence of dementia, history of diabetes mellitus and colonic disease, activity of daily living data include mobility, toileting and eating, use of percutaneous enterogastrostomy feeding, antibiotic administration, namely, type and duration, use of enema and laxatives, and use of proton pump inhibitors. RESULTS: Episodes of CDAD occurred mainly within the first year of admission to our facility, with a mean of 6 months, whereas the mean length of stay was 25 months in the control group (t = 3.452; df = 51; P < .01). Albumin level was another major risk factor for CDAD, with an overwhelming 68% of CDAD patients having albumin levels below 3 g/dL (mean 2.68 g/dL) compared with a mean of 3.22 g/dL in the control group (t = 4.210; df = 51; P < .001). The third significant risk factor was the use of proton pump inhibitors, 60% versus 32%, respectively (chi(2) = 4.137; df = 1; P < .05). Levofloxacin was the most frequently prescribed antibiotic (37%). Surprisingly, factors not associated with CDAD included dementia, diabetes mellitus, colonic disease, use of enema, use of laxatives, weight and body metabolic index, duration of previous antibiotic therapy for unrelated infection, mobility, toileting, and method of eating. CONCLUSION: A low albumin level, a recent admission to a nursing facility, and the use of proton pump inhibitors should be considered as probable risk factors for CDAD when assessing institutionalized patients with diarrhea. These findings may facilitate the timely and efficient management of CDAD in nursing home patients.     

Lack of association between the increased incidence of Clostridium difficile-associated disease and the increasing use of alcohol-based hand rubs.

OBJECTIVE: To determine whether there is an association between the increasing use of alcohol-based hand rubs (ABHRs) and the increased incidence of Clostridium difficile-associated disease (CDAD). SETTING: A 500-bed university-affiliated community teaching hospital. METHODS: Use of ABHRs during the period 2000-2003 was expressed as the number of liters of ABHR used per 1000 patient-days. The proportion of hand hygiene episodes performed by using an ABHR was determined by periodic observational surveys. CDAD was defined as a physician-ordered stool assay positive for C. difficile toxin A or A/B. The incidence of CDAD was expressed as the number of unique patients who had 1 or more positive CDAD test results per 1,000 patient-days. RESULTS: During 2000-2003, the use of ABHR increased 10-fold, from 3 to greater than 30 L/1,000 patient-days (P<.001). The proportion of hand hygiene episodes performed using an ABHR increased from 10% to 85% (P<.001). The incidence of CDAD in 2000, 2001, 2002, and 2003 was 1.74, 2.33, 1.14, and 1.18 cases/1,000 patient-days, respectively. CONCLUSION: Despite a significant and progressive increase in the use of ABHRs in our facility during a 3-year period, there was no evidence that the incidence of CDAD increased. These findings suggest that factors other than the increased use of ABHRs are responsible for the increasing incidence of CDAD noted since 2000 in other facilities.     

Clostridium difficile in the long-term care setting

The incidence of Clostridium difficile-associated disease (CDAD) has increased over the past few years and more severe cases of CDAD have been reported. This changing epidemiology is possibly a result of the emergence of a more virulent strain of C difficile that is more resistant to fluoroquinolones and is associated with increased morbidity and mortality. Because of advanced age and frequent courses of antibiotic therapy, patients in long-term care facilities are at increased risk of C difficile infection. In addition to beta-lactams and clindamycin, the fluoroquinolones have recently been associated with increased rates of CDAD. Early identification of C difficile infection and prompt initiation of therapy with the most appropriate agent are critical to minimize morbidity and mortality in this era of increasingly severe CDAD. Metronidazole and vancomycin have been the mainstays of therapy, and recent data support the expanding role of vancomycin in the treatment of severe CDAD. Adjunctive therapy with probiotics, intravenous immunoglobulin, or rifampin has been used in refractory or recurrent CDAD. Adherence to the recommended infection control measures and the judicious use of antibiotics should also be part of the global management of CDAD in long-term care facilities.     

Fluoroquinolones and risk for methicillin-resistant Staphylococcus aureus, Canada

Receipt of fluoroquinolones was the predominant risk factor for Clostridium difficile-associated disease (CDAD) during an epidemic in Quebec, Canada. To determine the role of antimicrobial drugs in facilitating healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection and to compare this role with their effects on methicillin-susceptible S. aureus infection and CDAD, we conducted a retrospective cohort study of patients in a Quebec hospital. For 7371 episodes of care, data were collected on risk factors, including receipt of antimicrobial drugs. Crude and adjusted hazard ratios (AHR) were calculated by Cox regression. Of 150 episodes of MRSA colonization and 23 of MRSA infection, fluoroquinolones were the only antimicrobials that increased risk for colonization (AHR 2.57, 95% confidence interval [CI] 1.84-3.60) and infection (AHR 2.49, 95% CI 1.02-6.07). Effect of antimicrobial drugs on MRSA colonization and infection was similar to effect on CDAD and should be considered when selecting antimicrobial drugs to treat common infections.     

Changing epidemiology of Clostridium difficile-associated disease in children.

OBJECTIVE: To determine temporal trends in the incidence rate for Clostridium difficile-associated disease (CDAD) in a pediatric patient population. METHODS: We performed an observational, retrospective cohort study that included children who visited or were admitted to Children's National Medical Center during the period from July 2001 through June 2006. The CDAD incidence rates were determined and examined for changes over time using the Poisson regression method. RESULTS: A total of 513 patients whose stool specimens tested positive for C. difficile toxin were identified. Of these patients, 61% were children aged 2 years or older. The proportion of patients with CDAD in this age group has steadily increased from 46% in 2001 to 64% in 2006. Largely as a result of an increasing number of cases of community-associated CDAD, the incidence of CDAD increased significantly in the outpatient setting, particularly in the emergency department (1.18 cases per 1,000 visits in 2001 vs 2.47 cases per 1,000 visits in 2006; P=.02). The incidence among inpatients decreased during the study period (1.024 cases per 1,000 patient-days in 2001 vs 0.680 cases per 1,000 patient-days in 2006; P=.004). In the neonatal intensive care unit, C. difficile toxin was detected in stool specimens collected from 22 patients aged from 15 days to 6 months. CONCLUSION: This study revealed a steady increase in the number of patients seen in the emergency department with community-acquired CDAD. Findings from this study suggest that the characteristics of CDAD in children--a population that has not been considered to be at high risk for this disease in the past--are changing. Further investigations are warranted to explore deviations from the established burdens of the disease and patient risk factors.     

Impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD) over a five-year period in a district general hospital

The impact of changes in antibiotic policy on Clostridium difficile-associated diarrhoea (CDAD), over a five-year period between 1995 and 2000, were studied in the Preston Acute Hospitals Trust. In 1996 the policy was changed in the Preston Acute Hospitals Trust from cefotaxime to ceftriaxone for initial treatment of severe sepsis or pneumonia in medical patients. Over the next nine months the average number of patients with C. difficile toxin-positive stools per quarter increased from 16 to 39. The predicted use of ceftriaxone exceeded by 65% an estimate based on prior use of cefotaxime. A policy of restricted duration of ceftriaxone was introduced, and although this reduced usage by over 50%, CDAD continued at an average of 9.2 cases per month, despite withdrawal of oral cephalosporins in December 1998. In August 1999 levofloxacin was substituted for ceftriaxone in the policy. The incidence of CDAD fell progressively to five cases per month by 2000. It would appear that a short (typically three dose) course of third-generation cephalosporin poses a similar risk for CDAD as a more prolonged course. The six-month delay in the decline of CDAD after virtual withdrawal of cephalosporins may reflect a slowly diminishing environmental reservoir.     

Assessment of Clostridium difficile-associated disease surveillance definitions, North Carolina, 2005.

OBJECTIVE: To determine the timing of community-onset Clostridium difficile-associated disease (CDAD) relative to the patient's last healthcare facility discharge, the association of postdischarge cases with healthcare facility-onset cases, and the influence of postdischarge cases on overall rates and interhospital comparison of rates of CDAD. DESIGN: Retrospective cohort study for the period January 1, 2005, through December 31, 2005. SETTING: Catchment areas of 6 acute care hospitals in North Carolina. METHODS: We reviewed medical and laboratory records to determine the date of symptom onset, the dates of hospitalization, and stool C. difficile toxin assay results for patients with CDAD who had diarrhea and positive toxin-assay results. Cases were classified as healthcare facility-onset if they were diagnosed more than 48 hours after admission. Cases were defined as community-onset if they were diagnosed in the community or within 48 hours after admission, and were also classified on the basis of the time since the last discharge: if within 4 weeks, community-onset, healthcare facility-associated (CO-HCFA); if 4-12 weeks, indeterminate exposure; and if more than 12 weeks, community-associated. Pearson's correlation coefficient was used to assess the association between monthly rates of healthcare facility-onset, healthcare facility-associated (HO-HCFA) cases and CO-HCFA cases. We performed interhospital rate comparisons using HO-HCFA cases only and using both HO-HCFA and CO-HCFA cases. RESULTS: Of 1046 CDAD cases, 442 (42%) were HO-HCFA cases and 604 (58%) were community-onset cases. Of the 604 community-onset cases, 94 (15%) were CO-HCFA, 40 (7%) were of indeterminate exposure, and 208 (34%) community-associated. A modest correlation was found between monthly rates of HO-HCFA cases and CO-HCFA cases across the 6 hospitals (r = 0.63, P < .001). Interhospital rankings changed for 6 of 11 months if CO-HCFA cases were included. CONCLUSIONS: A substantial proportion of community-onset cases of CDAD occur less than 4 weeks after discharge from a healthcare facility, and inclusion of CO-HCFA cases influences interhospital comparisons. Our findings support the use of a proposed definition of healthcare facility-associated CDAD that includes cases that occur within 4 weeks after discharge.