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Background: Antimicrobial susceptibility testing (AST) is not routinely performed for Clostridioides difficile and data evaluating minimum inhibitory concentrations (MICs) are limited. We performed AST and whole genome sequencing (WGS) for 593 C. difficile isolates collected between 2012 and 2017 through the Centers for Disease Control and Prevention's Emerging Infections Program., Methods: MICs to 6 antimicrobial agents (ceftriaxone, clindamycin, meropenem, metronidazole, moxifloxacin, and vancomycin) were determined using the reference agar dilution method according to Clinical and Laboratory Standards Institute guidelines. Whole genome sequencing was performed on all isolates to detect the presence of genes or mutations previously associated with resistance., Results: Among all isolates, 98.5% displayed a vancomycin MIC ≤2 μg/mL and 97.3% displayed a metronidazole MIC ≤2 μg/mL. Ribotype 027 (RT027) isolates displayed higher vancomycin MICs (MIC50: 2 μg/mL; MIC90: 2 μg/mL) than non-RT027 isolates (MIC50: 0.5 μg/mL; MIC90: 1 μg/mL) (P < .01). No vanA/B genes were detected. RT027 isolates also showed higher MICs to clindamycin and moxifloxacin and were more likely to harbor associated resistance genes or mutations., Conclusions: Elevated MICs to antibiotics used for treatment of C. difficile infection were rare, and there was no increase in MICs over time. The lack of vanA/B genes or mutations consistently associated with elevated vancomycin MICs suggests there are multifactorial mechanisms of resistance. Ongoing surveillance of C. difficile using reference AST and WGS to monitor MIC trends and the presence of antibiotic resistance mechanisms is essential., Competing Interests: Potential conflicts of interest . L. C. M. reports participation on a Data Safety Monitoring Board or Advisory Board for NIH/DMID (Protocol 19-0021: A Randomized, Double-blinded Evaluation of CRS3123 in Patients with Non-severe to Severe Clostridium difficile Infection). Emerging Infections Program C. difficile Infection Working Group authors: G. D. received grant funding from Pfizer Inc. S. F. received grant funding from Pfizer Inc. D. G. received consulting fees from Destiny Pharma PLC. M.K. reports an advisory role for the Clinical and Laboratory Standards Institute (CLSI) AST Subcommittee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Previously reported associations between hospital-level antibiotic use and hospital-onset Clostridioides difficile infection (HO-CDI) were reexamined using 2012-2018 data from a new cohort of US acute-care hospitals. This analysis revealed significant positive associations between total, third-generation, and fourth-generation cephalosporin, fluoroquinolone, carbapenem, and piperacillin-tazobactam use and HO-CDI rates, confirming previous findings.

Objectives: Diagnosing Clostridioides difficile infections in young children with high asymptomatic colonization is challenging. We compared the frequency of C difficile detection by polymerase chain reaction (PCR) in healthy control (HC) children with those with acute gastroenteritis (AGE) and evaluated fecal-lactoferrin and organism load as possible indicators of true C difficile infection disease., Methods: Stool was collected from children <2 years old with AGE and from HCs. C difficile was detected by real-time PCR, and lactoferrin was measured by enzyme-linked immunosorbent assay. Clinical data were obtained via interviews and chart review. Mann-Whitney U test and χ 2 tests were used for group comparisons., Results: Of 524 stools collected from 524 children (250 with AGE, 274 HCs), C difficile was detected less in children with AGE (14%, 36 of 250) than in HCs (28%, 76 of 274) stools ( P < .0001). Among infants <1 year old ( n = 297), C difficile was detected in 18% of children with AGE versus 32% of HCs ( P < .005), and among children 1 to 2 years old ( n = 227), C difficile was detected in 10% of children with AGE versus 21% of HCs ( P < .02). There was no significant difference in C difficile PCR cycle threshold values between children with AGE and HCs or lactoferrin levels in C difficile PCR-positive versus -negative stools., Conclusions: HC children <2 years of age had higher rates of C difficile detection by PCR than children with AGE; C difficile detection by real-time PCR alone is not a reliable means to diagnose C difficile disease in children <2 years old., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Background: Efforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear., Methods: The Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person ≥1 year of age with no positive test in the previous 8 weeks) in 10 U.S. sites. We used case and census sampling weights to estimate the national burden of C. difficile infection, first recurrences, hospitalizations, and in-hospital deaths from 2011 through 2017. Health care-associated infections were defined as those with onset in a health care facility or associated with recent admission to a health care facility; all others were classified as community-associated infections. For trend analyses, we used weighted random-intercept models with negative binomial distribution and logistic-regression models to adjust for the higher sensitivity of nucleic acid amplification tests (NAATs) as compared with other test types., Results: The number of cases of C. difficile infection in the 10 U.S. sites was 15,461 in 2011 (10,177 health care-associated and 5284 community-associated cases) and 15,512 in 2017 (7973 health care-associated and 7539 community-associated cases). The estimated national burden of C. difficile infection was 476,400 cases (95% confidence interval [CI], 419,900 to 532,900) in 2011 and 462,100 cases (95% CI, 428,600 to 495,600) in 2017. With accounting for NAAT use, the adjusted estimate of the total burden of C. difficile infection decreased by 24% (95% CI, 6 to 36) from 2011 through 2017; the adjusted estimate of the national burden of health care-associated C. difficile infection decreased by 36% (95% CI, 24 to 54), whereas the adjusted estimate of the national burden of community-associated C. difficile infection was unchanged. The adjusted estimate of the burden of hospitalizations for C. difficile infection decreased by 24% (95% CI, 0 to 48), whereas the adjusted estimates of the burden of first recurrences and in-hospital deaths did not change significantly., Conclusions: The estimated national burden of C. difficile infection and associated hospitalizations decreased from 2011 through 2017, owing to a decline in health care-associated infections. (Funded by the Centers for Disease Control and Prevention.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of US acute care hospitals (ACHs)., Methods: We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI (008.45), and treatment with metronidazole or oral vancomycin > 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics., Results: During 2006-2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10 000 patient-days (PD) (95% confidence interval [CI], 7.1-7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems, there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a ≥30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67 [95% CI, .47-.96]); ACHs with a ≥20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively., Conclusions: At an ecologic level, reductions in total AU, use of fluoroquinolones, and use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

A nationwide survey indicated that screening for asymptomatic carriers of C. difficile is an uncommon practice in US healthcare settings. Better understanding of the role of asymptomatic carriage in C. difficile transmission, and of the measures available to reduce that risk, are needed to inform best practices regarding the management of carriers.

The majority of paediatric Clostridioides difficile infections (CDI) are community-associated (CA), but few data exist regarding associated risk factors. We conducted a case-control study to evaluate CA-CDI risk factors in young children. Participants were enrolled from eight US sites during October 2014-February 2016. Case-patients were defined as children aged 1-5 years with a positive C. difficile specimen collected as an outpatient or ⩽3 days of hospital admission, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one control. Caregivers were interviewed regarding relevant exposures. Multivariable conditional logistic regression was performed. Of 68 pairs, 44.1% were female. More case-patients than controls had a comorbidity (33.3% vs. 12.1%; P = 0.01); recent higher-risk outpatient exposures (34.9% vs. 17.7%; P = 0.03); recent antibiotic use (54.4% vs. 19.4%; P &lt; 0.0001); or recent exposure to a household member with diarrhoea (41.3% vs. 21.5%; P = 0.04). In multivariable analysis, antibiotic exposure in the preceding 12 weeks was significantly associated with CA-CDI (adjusted matched odds ratio, 6.25; 95% CI 2.18-17.96). Improved antibiotic prescribing might reduce CA-CDI in this population. Further evaluation of the potential role of outpatient healthcare and household exposures in C. difficile transmission is needed.

INTRODUCTIONIn 2017, the Journal of Clinical Microbiology published a Point-Counterpoint on the laboratory diagnosis of Clostridium difficile infection (CDI). At that time, Ferric C. Fang, Christopher R. Polage, and Mark H. Wilcox discussed the strategies for diagnosing Clostridium difficile colitis in symptomatic patients (J Clin Microbiol 55:670-680, 2017, https://doi.org/10.1128/JCM.02463-16). Since that paper, new guidelines from the Infectious Diseases Society of America and the Society for Health Care Epidemiology have been published (L. C. McDonald, D. N. Gerding, S. Johnson, J. S. Bakken, K. C. Carroll, et al., Clin Infect Dis 66:987-994, 2018, https://doi.org/10.1093/cid/ciy149) and health care systems have begun to explore screening asymptomatic patients for C. difficile colonization. The theory behind screening selected patient populations for C. difficile colonization is that these patients represent a substantial reservoir of the bacteria and can transfer the bacteria to other patients. Hospital administrators are taking note of institutional CDI rates because they are publicly reported. They have become an important metric impacting hospital safety ratings and value-based purchasing, and hospitals may have millions of dollars of reimbursement at risk. In this Point-Counterpoint, Cliff McDonald of the U.S. Centers for Disease Control and Prevention discusses the value of asymptomatic C. difficile screening, while Dan Diekema of the University of Iowa discusses why caution should be used., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.

Background: Efforts to develop a Clostridium difficile vaccine are underway; identification of patients at risk for C. difficile infection (CDI) is critical to inform vaccine trials. We identified groups at high risk of CDI ≥ 2 8 days after hospital discharge., Methods: Hospital discharge data and pharmacy data from two large academic centers, in New York and Connecticut, were linked to active population-based CDI surveillance data from the Emerging Infections Program (EIP). Adult residents of the EIP surveillance area were included if they had an inpatient stay at a study hospital without prior history of CDI. The primary outcome was CDI by either toxin or molecular assay ≥ 28 days after an index hospitalization. Important predictors of CDI ≥ 28 days post discharge were initially identified through a Cox proportional hazards model (stepwise backward selection) using a derivation cohort; final model parameters were used to develop a risk score evaluated in the validation cohort., Results: Of the 35,186 index hospitalizations, 288 (0.82%) had CDI ≥ 28 days post discharge. After parameter selection, age, number of hospitalizations in the prior 90 days, admission diagnosis, and the use of 3rd/4th generation cephalosporin, clindamycin or fluoroquinolone antibiotic classes remained in the model. Using the validation cohort, the risk score was predictive (p<0.001) with a c-score of 0.75. Based on the distribution of scores in the derivation cohort, we divided the patients into low and high risk groups. In the high risk group, 1.6% experienced CDI ≥ 28 days post discharge compared to 0.3% among our low risk group., Conclusions: Our study identified specific parameters for a risk score that can be applied at discharge to identify a patient population whose risk of CDI ≥ 28 days following an acute care hospitalization was 5 times greater than other patients., (Published by Elsevier Ltd.)

Objective: To determine the potential epidemiologic and economic value of the implementation of a multifaceted Clostridium difficile infection (CDI) control program at US acute care hospitals, Design: Markov model with a 5-year time horizon, Participants: Patients whose data were used in our simulations were limited to hospitalized Medicare beneficiaries ≥65 years old., Background: CDI is an important public health problem with substantial associated morbidity, mortality, and cost. Multifaceted national prevention efforts in the United Kingdom, including antimicrobial stewardship, patient isolation, hand hygiene, environmental cleaning and disinfection, and audit, resulted in a 59% reduction in CDI cases reported from 2008 to 2012., Methods: Our analysis was conducted from the federal perspective. The intervention we modeled included the following components: antimicrobial stewardship utilizing the Antimicrobial Use and Resistance module of the National Healthcare Safety Network (NHSN), use of contact precautions, and enhanced environmental cleaning. We parameterized our model using data from CDC surveillance systems, the AHRQ Healthcare Cost and Utilization Project, and literature reviews. To address uncertainty in our parameter estimates, we conducted sensitivity analyses for intervention effectiveness and cost, expenditures by other federal partners, and discount rate. Each simulation represented a cohort of 1,000 hospitalized patients over 1,000 trials. RESULTS In our base case scenario with 50% intervention effectiveness, we estimated that 509,000 CDI cases and 82,000 CDI-attributable deaths would be prevented over a 5-year time horizon. Nationally, the cost savings across all hospitalizations would be $2.5 billion (95% credible interval: $1.2 billion to $4.0 billion)., Conclusions: The potential benefits of a multifaceted national CDI prevention program are sizeable from the federal perspective.

Objective: To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission, Design: Retrospective data analysis, Setting: Six US acute care hospitals, Patients: Adult inpatients, Methods: We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations., Results: Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001)., Conclusion: Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Objective: Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children ≤3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups., Methods: Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile-positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or ≤3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years., Results: Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100,000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks., Conclusions: Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized.

A commercial PCR assay of perirectal swab specimens detected 17 (68%) of 25 asymptomatic carriers of toxigenic Clostridium difficile, including 93% with skin and/or environmental contamination. A clinical prediction rule, followed by PCR screening, could be used to identify carriers at high risk of C. difficile shedding.

Importance: Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood., Objectives: To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community., Design and Setting: Active population-based and laboratory-based CDI surveillance in 8 US states., Participants: Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care)., Main Outcomes and Measures: Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure., Results: Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%)., Conclusions and Relevance: Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use.

Objective:  To determine the attributable in-hospital mortality, length of stay (LOS), and cost of hospital-onset Clostridium difficile infection (HO-CDI)., Design:  Propensity score matching., Setting:  Six Pennsylvania hospitals (2 academic centers, 1 community teaching facility, and 3 community nonteaching facilities) contributing data to a clinical research database., Patients:  Adult inpatients between 2007 and 2008., Methods:  We defined HO-CDI in adult inpatients as a positive C. difficile toxin assay result from a specimen collected more than 48 hours after admission and more than 8 weeks following any previous positive result. We developed an HO-CDI propensity model and matched cases with noncases by propensity score at a 1∶3 ratio. We further restricted matching within the same hospital, within the same principal disease group, and within a similar length of lead time from admission to onset of HO-CDI., Results:  Among 77,257 discharges, 282 HO-CDI cases were identified. The propensity score-matched rate was 90%. Compared with matched noncases, HO-CDI patients had higher mortality (11.8% vs. 7.3%; P < .05), longer LOS (median [interquartile range (IQR)], 12 [9-21] vs. 11 [8-17] days; P < .01), and higher cost (median [IQR], $20,804 [$11,059-$38,429] vs. $16,634 [$9,413-$30,319]; P < .01). The attributable effect of HO-CDI was 4.5% (95% confidence interval [CI], 0.2%-8.7%; P < .05) for mortality, 2.3 days (95% CI, 0.9-3.8; P < .01) for LOS, and $6,117 (95% CI, $1,659-$10,574; P < .01) for cost., Conclusions:  Patients with HO-CDI incur additional attributable mortality, LOS, and cost burden compared with patients with similar primary clinical condition, exposure risk, lead time of hospitalization, and baseline characteristics.

Background: Long-term care facility (LTCF) residents are at increased risk of Clostridium difficile infection (CDI). However, little is known about the incidence, recurrence, and severity of CDI in LTCFs or the extent to which acute care exposure contributes to CDI in LTCFs. We describe the epidemiology of CDI in a cohort of LTCF residents in Monroe County, New York, where recent estimates suggest a CDI incidence in hospitals of 9.2 cases per 10,000 patient-days., Design: Population-based surveillance study., Setting: Monroe County, New York. Patients. LTCF residents with onset of CDI while in the LTCF or less than 4 calendar-days after hospital admission from the LTCF from January 1 through December 31, 2010., Methods: We conducted surveillance for CDI in residents of 33 LTCFs. A CDI case was defined as a stool specimen positive for C. difficile obtained from a patient without a C. difficile-positive specimen in the previous 8 weeks; recurrence was defined as a stool specimen positive for C. difficile obtained between 2 and 8 weeks after the last C. difficile-positive stool specimen., Results: There were 425 LTCF-onset cases and 184 recurrences, which yielded an incidence of 2.3 cases per 10,000 resident-days (interquartile range [IQR], 1.2-3.3) and a recurrence rate of 1.0 case per 10,000 resident-days (IQR, 0.3-1.4). The cases occurred in 394 LTCF residents, and 52% of these residents developed CDI within 4 weeks after hospital discharge. Hospitalization for CDI occurred in 70 cases (16%). Of those cases that involved hospitalization for CDI, 70% were severe CDI, and 23% ended in death within 30 days after hospital admission., Conclusion: CDI incidence in Monroe County LTCFs is one-fourth the incidence among hospitalized patients. Approximately 50% of LTCF-onset cases occurred more than 4 weeks after hospital discharge, which emphasizes that prevention of CDI transmission should go beyond acute care settings.

The dramatic changes in the epidemiology of Clostridium difficile infection (CDI) during recent years, with increases in incidence and severity of disease in several countries, have made CDI a global public health challenge. Increases in CDI incidence have been largely attributed to the emergence of a previously rare and more virulent strain, BI/NAP1/027. Increased toxin production and high-level resistance to fluoroquinolones have made this strain a very successful pathogen in healthcare settings. In addition, populations previously thought to be at low risk are now being identified as having severe CDI. Recent genetic analysis suggests that C. difficile has a highly fluid genome with multiple mechanisms to modify its content and functionality, which can make C. difficile adaptable to environmental changes and potentially lead to the emergence of more virulent strains. In the face of these changes in the epidemiology and microbiology of CDI, surveillance systems are necessary to monitor trends and inform public health actions.

Background: Globally, gastroenteritis is recognized as an important contributor to mortality among children, but population-based data on gastroenteritis deaths among adults and the contributions of specific pathogens are limited. We aimed to describe trends in gastroenteritis deaths across all ages in the United States and specifically estimate the contributions of Clostridium difficile and norovirus., Methods: Gastroenteritis-associated deaths in the United States during 1999-2007 were identified from the National Center for Health Statistics multiple-cause-of-death mortality data. All deaths in which the underlying cause or any of the contributing causes listed gastroenteritis were included. Time-series regression models were used to identify cause-unspecified gastroenteritis deaths that were probably due to specific causes; seasonality of model residuals was analyzed to estimate norovirus-associated deaths., Results: Gastroenteritis mortality averaged 39/1000000 person-years (11 255 deaths per year) during the study period, increasing from 25/1 000 000 person-years in 1999-2000 to 57/1 000 000 person-years in 2006-2007 (P < .001). Adults aged ≥ 65 years accounted for 83% of gastroenteritis deaths (258/1 000 000 person-years). C. difficile mortality increased 5-fold from 10/1 000 000 person-years in 1999-2000 to 48/1 000 000 person-years in 2006-2007 (P < .001). Norovirus contributed to an estimated 797 deaths annually (3/1 000 000 person-years), with surges by up to 50% during epidemic seasons associated with emergent viral strains., Conclusions: Gastroenteritis-associated mortality has more than doubled during the past decade, primarily affecting the elderly. C. difficile is the main contributor to gastroenteritis-associated deaths, largely accounting for the increasing trend, and norovirus is probably the second leading infectious cause. These findings can help guide appropriate clinical management strategies and vaccine development.

Clostridium difficile, the most commonly recognized diarrheagenic pathogen among hospitalized persons, can cause outpatient diarrhea. Of 1,091 outpatients with diarrhea, we found 43 (3.9%) who were positive for C. difficile toxin. Only 7 had no recognized risk factors, and 3 had neither risk factors nor co-infection with another enteric pathogen.

Background: Expanding hospitalized patients' risk stratification for Clostridium difficile infection (CDI) is important for improving patient safety. We applied definitions for hospital-onset (HO) and community-onset (CO) CDI to electronic data from 85 hospitals between January 2007 and June 2008 to identify factors associated with higher HO CDI rates., Methods: Nonrecurrent CDI cases were identified among adult (≥ 18-year-old) inpatients by a positive C. difficile toxin assay result more than 8 weeks after any previous positive result. Case categories included HO, CO-hospital associated (CO-HA), CO-indeterminate hospital association (CO-IN), and CO-non-hospital associated (CO-NHA). C. difficile testing intensity (CDTI) was defined as the total number of C. difficile tests performed, normalized to the number of patients with at least 1 C. difficile toxin test recorded. We calculated both the incidence density and the prevalence of CDI where appropriate. We fitted a multivariable Poisson model to identify factors associated with higher HO CDI rates., Results: Among 1,351,156 unique patients with 2,022,213 admissions, 9,803 cases of CDI were identified; of these, 50.6% were HO, 17.4% were CO-HA, 9.0% were CO-IN, and 23.0% were CO-NHA. The incidence density of HO was 6.3 per 10,000 patient-days. The prevalence of CO CDI on admission was, per 10,000 admissions, 8.4 for CO-HA, 4.4 for CO-IN, and 11.1 for CO-NHA. Factors associated (P < .0001) with higher HO CDI rates included older age, higher CO-NHA prevalence on admission, and increased CDTI., Conclusion: Electronic health information can be leveraged to risk-stratify HO CDI rates by patient age and CO-NHA prevalence on admission. Hospitals should optimize diagnostic testing to improve patient care and measured CDI rates.

We used data from the Kids' Inpatient Database to examine Clostridium difficile infection (CDI) among children with cancer. The CDI rate was 15 times greater among children with cancer compared with those without cancer. Children with cancer accounted for 21% of all pediatric CDI cases. Increased adherence to infection control recommendations is needed to address CDI in children with cancer.

Background: The epidemiology of community-associated Clostridium difficile infection is not well known. We performed a multicenter, case-control study to further describe community-associated C. difficile infection and assess novel risk factors., Methods: We conducted this study at 5 sites from October 2006 through November 2007. Community-associated C. difficile infection included individuals with diarrhea, a positive C. difficile toxin, and no recent (12 weeks) discharge from a health care facility. We selected controls from the same clinics attended by cases. We collected clinical and exposure data at the time of illness and cultured residual stool samples and performed ribotyping., Results: Of 1041 adult C. difficile infections, 162 (15.5%) met criteria for community-associated: 66 case and 114 control patients were enrolled. Case patients were relatively young (median 64 years), female (56%), and frequently required hospitalization (38%). Antimicrobials, malignancy, exposure to high-risk persons, and remote health care exposure were independently associated with community-associated C. difficile infection. In 40% of cases, we could not confirm recent antibiotic exposure. Stomach-acid suppressants were not associated with community-associated infection, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors appeared protective. Prevalence of the hypervirulent NAP-1/027 strain was infrequent (17%)., Conclusions: Community-associated C. difficile infection resulted in a substantial health care burden. Antimicrobials are a significant risk factor for community-associated infection. However, other unique factors also may contribute, including person-to-person transmission, remote health care exposures, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. A role for stomach-acid suppressants in community-associated C. difficile infection is not supported., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the feasibility of using electronic laboratory and admission-discharge-transfer data from BioSense, a national automated surveillance system, to apply new modified Clostridium difficile infection (CDI) surveillance definitions and calculate overall and facility-specific rates of disease., Design: Retrospective, multicenter cohort study., Setting: Thirty-four hospitals sending inpatient, emergency department, and/or outpatient data to BioSense., Methods: Laboratory codes and text-parsing methods were used to extract C. difficile-positive toxin assay results from laboratory data sent to BioSense during the period from January 1, 2007, through June 30, 2008; these were merged with administrative records to determine whether cases were community associated or healthcare onset, as well as patient-day data for rate calculations. A patient was classified as having hospital-onset CDI if he or she had a C. difficile toxin-positive result on a stool sample collected 3 or more days after admission and community-onset CDI if the specimen was collected less than 3 days after admission or the patient was not hospitalized., Results: A total of 4,585 patients from 34 hospitals in 12 states had C. difficile-positive assay results. More than half (53.0%) of the cases were community-onset, and 30.8% of these occurred in patients who were recently hospitalized. The overall rate of healthcare-onset CDI was 7.8 cases per 10,000 patient-days, with a range among facilities of 1.5-27.8 cases per 10,000 patient-days., Conclusions: Electronic laboratory data sent to the BioSense surveillance system were successfully used to produce disease rates of CDI comparable to those of other studies, which shows the feasibility of using electronic laboratory data to track a disease of public health importance.

Since publication of the Society for Healthcare Epidemiology of America position paper on Clostridium difficile infection in 1995, significant changes have occurred in the epidemiology and treatment of this infection. C. difficile remains the most important cause of healthcare-associated diarrhea and is increasingly important as a community pathogen. A more virulent strain of C. difficile has been identified and has been responsible for more-severe cases of disease worldwide. Data reporting the decreased effectiveness of metronidazole in the treatment of severe disease have been published. Despite the increasing quantity of data available, areas of controversy still exist. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, and infection control and environmental management.

Objective: To compare incidence of hospital-onset Clostridium difficile infection (CDI) measured by the use of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) discharge diagnosis codes with rates measured by the use of electronically available C. difficile toxin assay results., Methods: Cases of hospital-onset CDI were identified at 5 US hospitals during the period from July 2000 through June 2006 with the use of 2 surveillance definitions: positive toxin assay results (gold standard) and secondary ICD-9-CM discharge diagnosis codes for CDI. The chi(2) test was used to compare incidence, linear regression models were used to analyze trends, and the test of equality was used to compare slopes., Results: Of 8,670 cases of hospital-onset CDI, 38% were identified by the use of both toxin assay results and the ICD-9-CM code, 16% by the use of toxin assay results alone, and 45% by the use of the ICD-9-CM code alone. Nearly half (47%) of cases of CDI identified by the use of a secondary diagnosis code alone were community-onset CDI according to the results of the toxin assay. The rate of hospital-onset CDI found by use of ICD-9-CM codes was significantly higher than the rate found by use of toxin assay results overall (P < .001), as well as individually at 3 of the 5 hospitals (P < .001 for all). The agreement between toxin assay results and the presence of a secondary ICD-9-CM diagnosis code for CDI was moderate, with an overall kappa value of 0.509 and hospital-specific kappa values of 0.489-0.570. Overall, the annual increase in CDI incidence was significantly greater for rates determined by the use of ICD-9-CM codes than for rates determined by the use of toxin assay results (P = .006)., Conclusions: Although the ICD-9-CM code for CDI seems to be adequate for measuring the overall CDI burden, use of the ICD-9-CM discharge diagnosis code for CDI, without present-on-admission code assignment, is not an acceptable surrogate for surveillance for hospital-onset CDI.

Clostridium difficile isolates from presumed community-associated infections (n = 92) were characterized by toxinotyping, pulsed-field gel electrophoresis, tcdC and cdtB PCR, and antimicrobial susceptibility. Nine toxinotypes (TOX) and 31 PFGE patterns were identified. TOX 0 (48, 52%), TOX III (18, 20%), and TOX V (9, 10%) were the most common; three isolates were nontoxigenic.

Context: Healthcare data suggest that the incidence and severity of Clostridium difficile infection (CDI) in hospitals are increasing. However, the overall burden of disease and the mortality rate associated with CDI, including the contribution from cases of infection that occur in nursing homes, are poorly understood., Objective: To describe the epidemiology, disease burden, and mortality rate of healthcare-onset CDI., Methods: In 2006, active public reporting of healthcare-onset CDI, using standardized case definitions, was mandated for all Ohio hospitals and nursing homes. Incidence rates were determined and stratified according to healthcare facility characteristics. Death certificates that listed CDI were analyzed for trends., Results: There were 14,329 CDI cases reported, including 6,376 cases at 210 hospitals (5,217 initial cases [ie, cases identified more than 48 hours after admission to a healthcare facility in patients who had not had CDI during the previous 6 months] and 1,159 recurrent cases [ie, cases involving patients who had had CDI during the previous 6 months]) and 7,953 cases at 955 nursing homes (4,880 initial and 3,073 recurrent cases) . After adjusting for missing data, the estimated total was 18,200 cases of CDI, which included 7,000 hospital cases (5,700 initial and 1,300 recurrent cases) and 11,200 nursing homes cases (6,900 initial and 4,300 recurrent cases). The rate for initial cases was 6.4-7.9 cases/10,000 patient-days for hospitals and 1.7-2.9 cases/10,000 patient-days for nursing homes. The rate for initial cases in nursing homes decreased during the study (P < .001). Nonpediatric hospital status (P = .011), a smaller number of beds (P = .003), and location in the eastern or northeastern region of the state (P = .011) were each independently associated with a higher rate of initial cases in hospitals. Death certificates for 2006 listed CDI among the causes of death for 893 Ohio residents; between 2000 and 2006, this number increased more than 4-fold., Conclusion: Healthcare-onset CDI represents a major public health threat that, when considered in the context of an increasing mortality rate, should justify a major focus on prevention efforts.

Objective: To evaluate the impact of cases of community-onset, healthcare facility (HCF)-associated Clostridium difficile infection (CDI) on the incidence and outbreak detection of CDI., Design: A retrospective multicenter cohort study., Setting: Five university-affiliated, acute care HCFs in the United States., Methods: We collected data (including results of C. difficile toxin assays of stool samples) on all of the adult patients admitted to the 5 hospitals during the period from July 1, 2000, through June 30, 2006. CDI cases were classified as HCF-onset if they were diagnosed more than 48 hours after admission or as community-onset, HCF-associated if they were diagnosed within 48 hours after admission and if the patient had recently been discharged from the HCF. Four surveillance definitions were compared: cases of HCF-onset CDI only (hereafter referred to as HCF-onset CDI) and cases of HCF-onset and community-onset, HCF-associated CDI diagnosed within 30, 60, and 90 days after the last discharge from the study hospital (hereafter referred to as 30-day, 60-day, and 90-day CDI, respectively). Monthly CDI rates were compared. Control charts were used to identify potential CDI outbreaks., Results: The rate of 30-day CDI was significantly higher than the rate of HCF-onset CDI at 2 HCFs (P < .01). The rates of 30-day CDI were not statistically significantly different from the rates of 60-day or 90-day CDI at any HCF. The correlations between each HCF's monthly rates of HCF-onset CDI and 30-day CDI were almost perfect (rho range, 0.94-0.99; P < .001). Overall, 12 time points had a CDI rate that was more than 3 standard deviations above the mean, including 11 time points identified using the definition for HCF-onset CDI and 9 time points identified using the definition for 30-day CDI, with discordant results at 4 time points ((kappa = 0.794; P < .001)., Conclusions: Tracking cases of both community-onset and HCF-onset, HCF-associated CDI captures significantly more CDI cases, but surveillance of HCF-onset, HCF-associated CDI alone is sufficient to detect an outbreak.

We previously reported Clostridium difficile in 20% of retail meat in Canada, which raised concerns about potential foodborne transmissibility. Here, we studied the genetic diversity of C. difficile in retail meats, using a broad Canadian sampling infrastructure and 3 culture methods. We found 6.1% prevalence and indications of possible seasonality (highest prevalence in winter).

To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.

Objective: To review the effect of interventions, including a complete restriction in the use of fluoroquinolones (FQs), used to control an outbreak of hospital-onset Clostridium difficile infection (HO-CDI) caused primarily by the epidemic North American pulsed-field gel electrophoresis type 1 strain., Design: Retrospective cohort and case-control study of all episodes of HO-CDI both before and after 2 interventions., Setting: Community hospital; January 1, 2005, through March 31, 2007. Interventions. Complete, 5-month, facility-wide restriction of fluoroquinolone use, during which a change in the environmental-services contractor occurred., Results: During a 27-month period, 319 episodes of HO-CDI occurred. The hospital-wide mean defined daily doses of antimicrobials decreased 22% after restricting FQ use, primarily because of a 66% decrease in the use of FQs. The interventions were also associated with a significant change in the HO-CDI incidence trends and with an absolute decrease of 22% in HO-CDI cases caused by the epidemic strain (from 66% before the intervention period to 44% during and after the intervention period; P=.02). Univariate analysis revealed that case patients with HO-CDI due to the epidemic strain were more likely than control patients, who did not have diarrhea, to receive a FQ, whereas case patients with HO-CDI due to a nonepidemic strain were not. However, FQ use was not significantly associated with HO-CDI in multivariable analysis., Conclusions: An outbreak of epidemic-strain HO-CDI was controlled at a community hospital after an overall decrease in antimicrobial use, primarily because of a restriction of FQ use and a change in environmental-services contractors. The restriction of FQ use may be useful as an adjunct control measure in a healthcare facilities during outbreaks of epidemic-strain HO-CDI.

Objective: To determine whether hydrogen peroxide vapor (HPV) decontamination can reduce environmental contamination with and nosocomial transmission of Clostridium difficile., Design: A prospective before-after intervention study., Setting: A hospital affected by an epidemic strain of C. difficile., Intervention: Intensive HPV decontamination of 5 high-incidence wards followed by hospital-wide decontamination of rooms vacated by patients with C. difficile-associated disease (CDAD). The preintervention period was June 2004 through March 2005, and the intervention period was June 2005 through March 2006., Results: Eleven (25.6%) of 43 cultures of samples collected by sponge from surfaces before HPV decontamination yielded C. difficile, compared with 0 of 37 cultures of samples obtained after HPV decontamination (P < .001). On 5 high-incidence wards, the incidence of nosocomial CDAD was significantly lower during the intervention period than during the preintervention period (1.28 vs 2.28 cases per 1,000 patient-days; P = .047). The hospital-wide CDAD incidence was lower during the intervention period than during the preintervention period (0.84 vs 1.36 cases per 1,000 patient-days; P = .26). In an analysis limited to months in which the epidemic strain was present during both the preintervention and the intervention periods, CDAD incidence was significantly lower during the intervention period than during the preintervention period (0.88 vs 1.89 cases per 1,000 patient-days; P = .047)., Conclusions: HPV decontamination was efficacious in eradicating C. difficile from contaminated surfaces. Further studies of the impact of HPV decontamination on nosocomial transmission of C. difficile are warranted.

Clostridium difficile is a recognized pathogen in neonatal pigs and may contribute to enteritis in calves. Toxinotype V strains have been rare causes of human C. difficile-associated disease (CDAD). We examined toxinotype V in human disease, the genetic relationship of animal and human toxinotype V strains, and in vitro toxin production of these strains. From 2001 through 2006, 8 (1.3%) of 620 patient isolates were identified as toxinotype V; before 2001, 7 (<0.02%) of approximately 6,000 isolates were identified as toxinotype V. Six (46.2%) of 13 case-patients for whom information was available had community-associated CDAD. Molecular characterization showed a high degree of similarity between human and animal toxinotype V isolates; all contained a 39-bp tcdC deletion and most produced binary toxin. Further study is needed to understand the epidemiology of CDAD caused by toxinotype V C. difficile, including the potential of foodborne transmission to humans.

Data are limited on the attributable outcomes of Clostridium difficile-associated disease (CDAD), particularly in CDAD-endemic settings. We conducted a retrospective cohort study of nonsurgical inpatients admitted for >/=48 hours in 2003 (N = 18,050). The adjusted hazard ratios for readmission (hazard ratio 2.19, 95% confidence interval [CI] 1.87-2.55) and deaths within 180 days (hazard ratio 1.23, 95% CI 1.03-1.46) were significantly different among CDAD case-patients and noncase patients. In a propensity score matched-pairs analysis that used a nested subset of the cohort (N = 706), attributable length of stay attributable to CDAD was 2.8 days, attributable readmission at 180 days was 19.3%, and attributable death at 180 days was 5.7%. CDAD patients were significantly more likely than controls to be discharged to a long-term-care facility or outside hospital. Even in a nonoutbreak setting, CDAD had a statistically significant negative impact on patient illness and death, and the impact of CDAD persisted beyond hospital discharge.

Objective: To estimate if Clostridium difficile-associated disease (CDAD) is increasing in peripartum women., Study Design: Peripartum CDAD was assessed through 1) passive surveillance collecting clinical and pathology data on severe cases and 2) survey among infectious disease consultants (ICDs) in the Emerging Infections Network., Results: Ten severe cases were collected; most had associated antibiotic use. Seven women were either admitted to the ICU or underwent colectomy. Three infants were stillborn, and 3 women died. The epidemic Clostridium difficile strain was found in 2 cases. Among 798 ICDs, 419 (52%) participated in the survey. Thirty-seven respondents (9%) recalled 55 cases, mostly in the postpartum period with 21 complications, mainly due to relapse., Conclusion: Severe CDAD may be increasing in peripartum women. Clinicians should have a low threshold for testing, be aware of the potential for severe outcomes, and take steps to reduce both the risk of disease and resultant complications.

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.

Background: The incidence of Clostridium difficile-associated disease (CDAD) is increasing. There are few data on the short-term and long-term attributable costs of CDAD. The objective of this study was to determine the acute and 180-day attributable inpatient costs of CDAD., Methods: We performed a retrospective cohort study of all patients without operating room costs who were admitted for > or =48 h to Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, Missouri, 1 January 2003-31 December 2003 (n = 24,691). Attributable costs of CDAD were determined by multivariable linear regression and propensity-score matched-pairs analyses (n = 684) for the hospitalization in which CDAD occurred and per patient over a 180-day period, including the initial hospitalization., Results: CDAD was associated with $2454 (95% confidence interval, $2380-$2950; increase in cost, 41%) attributable costs per CDAD episode by linear regression and with $3240 attributable costs (P < .001; increase in cost, 33%) by propensity-score matched-pairs analysis. CDAD was associated with $5042 (95% confidence interval, $3797-$6481; increase in cost, 53%) attributable inpatient costs over 180 days by linear regression and with $7179 attributable costs for inpatient care (P < .001; 48% increase in costs) by propensity-score matched-pairs analysis., Conclusions: CDAD was associated with a significant increase in costs for inpatient care and increased costs at 180 days after the initial hospitalization when the CDAD episode occurred.

Using 42 isolates contributed by laboratories in Canada, The Netherlands, the United Kingdom, and the United States, we compared the results of analyses done with seven Clostridium difficile typing techniques: multilocus variable-number tandem-repeat analysis (MLVA), amplified fragment length polymorphism (AFLP), surface layer protein A gene sequence typing (slpAST), PCR-ribotyping, restriction endonuclease analysis (REA), multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). We assessed the discriminating ability and typeability of each technique as well as the agreement among techniques in grouping isolates by allele profile A (AP-A) through AP-F, which are defined by toxinotype, the presence of the binary toxin gene, and deletion in the tcdC gene. We found that all isolates were typeable by all techniques and that discrimination index scores for the techniques tested ranged from 0.964 to 0.631 in the following order: MLVA, REA, PFGE, slpAST, PCR-ribotyping, MLST, and AFLP. All the techniques were able to distinguish the current epidemic strain of C. difficile (BI/027/NAP1) from other strains. All of the techniques showed multiple types for AP-A (toxinotype 0, binary toxin negative, and no tcdC gene deletion). REA, slpAST, MLST, and PCR-ribotyping all included AP-B (toxinotype III, binary toxin positive, and an 18-bp deletion in tcdC) in a single group that excluded other APs. PFGE, AFLP, and MLVA grouped two, one, and two different non-AP-B isolates, respectively, with their AP-B isolates. All techniques appear to be capable of detecting outbreak strains, but only REA and MLVA showed sufficient discrimination to distinguish strains from different outbreaks.

In recent years, the incidence and severity of Clostridium difficile-associated disease (CDAD) have increased dramatically. Beginning in 2000, widespread regional outbreaks associated with a previously uncommon hypervirulent strain of C. difficile have occurred in North America and Europe. Most likely because of increased toxin production as well as other virulence factors, this epidemic strain has caused more severe and refractory disease leading to complications, including intensive care unit admission, colectomies, and death. Worldwide increasing use of fluoroquinolones and cephalosporins has likely contributed to the proliferation of this epidemic strain, which is highly resistant to both. The elderly have been disproportionately affected by CDAD, but C. difficile has also recently emerged in populations previously considered to be at low risk, including healthy outpatients and peripartum women, although it is unknown if these cases are related to the epidemic strain. Nevertheless, transmission within hospitals is the major source of C. difficile acquisition, and previous or concurrent antimicrobial use is almost universal among cases. Applying current evidence-based strategies for management and prevention is critically important, and clinicians should maintain an awareness of the changing epidemiology of CDAD and take measures to reduce the risk of disease in patients.