Cost-Benefit Analysis of Allowing Additional Time in Cleaning Hospital Contact Precautions Rooms.

Increasing cleaning time may reduce hospital-acquired transmission of Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococcus (VRE). We constructed a cost-benefit model to estimate the impact of implementing an enhanced cleaning protocol, allowing hospital housekeepers an additional 15 minutes to terminally clean contact precautions rooms. The enhanced cleaning protocol saved the hospital $758 per terminally-cleaned room when accounting for only C. difficile. Scaling up to a hospital with 100 cases of C. difficile/year, and the US annual C. difficile incidence, cost savings were $75,832/year and $169.8 million/year, respectively. These results may inform infection control strategic decision-making and resource allocation.

One Health approach to Clostridioides difficile in Japan.

Clostridioides difficile infections (CDIs) are predominantly a healthcare-associated illness in developed countries, with the majority of cases being elderly and hospitalize patients who used antibiotic therapy. Recently, the incidence of community-associated CDIs (CA-CDIs) in younger patients without a previous history of hospitalization or antibiotic treatment has been increasing globally. C. difficile is sometimes found in the intestine of many animals, such as pigs, calves, and dogs. Food products such as retail meat products and vegetables sometimes contain C. difficile. C. difficile has also been isolated from several environments such as compost manure, rivers, and soils. Yet, direct transmission of C. difficile from animals, food products, and environments to humans has not been proven, although these strains have similar molecular characteristics. Therefore, it has been suggested that there is a relationship between CA-CDIs and C. difficile from animals, food products, and the environment. To clarify the importance of the presence of C. difficile in several sources, characterization of C. difficile in these sources is required. However, the epidemiology of C. difficile in animals, food products, and the environment is not well studied in Japan. This review summarizes recent trends of CDIs and compares the molecular characteristics of C. difficile in Japanese animals, food products, and the environment. The prevalence trends of C. difficile in Japan are similar to those in the rest of the world. Therefore, I recommend using a One Health approach to CDI surveillance, monitoring, and control.

Navigating changes in Clostridioides difficile prevention and treatment.

Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.

Comparative assessment of the therapeutic drug targets of C. botulinum ATCC 3502 and C. difficile str. 630 using in silico subtractive proteomics approach.

Growing antimicrobial resistance of the pathogens against multiple drugs posed a serious threat to the human health worldwide. This fueled the need of identifying the novel therapeutic targets that can be used for developing new class of the drugs. Recently, there is a substantial rise in the rate of Clostridium infections as well as in the emergence of virulent and antibiotic resistant strains. Hence, there is an urgent need for the identification of potential therapeutic targets and the development of new drugs for the treatment and prevention of Clostridium infections. In the present study, a combinatorial approach involving systems biology and comparative genomics strategy was tested against Clostridium botulinum ATCC 3502 and Clostridium difficile str. 630 pathogens, to render potential therapeutic target at qualitative and quantitative level. This resulted in the identification of five common (present in both the pathogens, 34 in C. botulinum ATCC 3502 and 42 in C. difficile str. 630) drug targets followed by virtual screening-based identification of potential inhibitors employing molecular docking and molecular dynamics simulations. The identified targets will provide a solid platform for the designing of novel wide-spectrum lead compounds capable of inhibiting their catalytic activities against multidrug-resistant Clostridium in the near future.

Clostridium difficile co-infection in inflammatory bowel disease is associated with significantly increased in-hospital mortality.

OBJECTIVE: Inflammatory bowel disease (IBD) patients with Clostridium difficile co-infection (CDCI) have an increased risk of morbidity and mortality. We aim to evaluate the impact of CDCI on in-hospital outcomes among adults with IBD hospitalized in the USA. PATIENTS AND METHODS: Using the 2007-2013 Nationwide Inpatient Sample, hospitalizations among US adults with Crohn's disease (CD), ulcerative colitis (UC) and CDCI were identified using ICD-9 coding. Hospital charges, hospital length of stay (LOS), and in-hospital mortality was stratified by CD and UC and compared using χ-testing and Student's t-test. Predictors of hospital charges, LOS, and in-hospital mortality were evaluated with multivariate regression models and were adjusted for age, sex, race/ethnicity, year, insurance status, hospital characteristics, and CDCI. RESULTS: Among 224 500 IBD hospitalizations (174 629 CD and 49 871 UC), overall prevalence of CDCI was 1.22% in CD and 3.41% in UC. On multivariate linear regression, CDCI was associated with longer LOS among CD [coefficient: 5.30, 95% confidence interval (CI): 4.61-5.99, P<0.001] and UC (coefficient 4.08, 95% CI: 3.54-4.62, P<0.001). Higher hospital charges associated with CDCI were seen among CD (coefficient: $35 720, 95% CI: $30 041-$41 399, P<0.001) and UC (coefficient: $26 009, 95% CI: $20 970-$31 046, P<0.001). On multivariate logistic regression, CDCI was associated with greater risk of in-hospital mortality (CD: odds ratio: 2.74, 95% CI: 1.94-3.87, P<0.001; UC: OR: 5.50, 95% CI: 3.83-7.89, P<0.001). CONCLUSION: Among US adults with CD and UC related hospitalizations, CDCI is associated with significantly greater in-hospital mortality and greater healthcare utilization.

Clinical and economic impact of the introduction of a nucleic acid amplification assay for Clostridium difficile.

BACKGROUND: The clinical outcomes and cost implications of a diagnostic shift from an EIA- to PCR-based assay for Clostridium difficile infection (CDI) have not been completely described in the literature. METHODS: The impact of the PCR-based assay on the incidence and duration of CDI therapy was compared to the EIA assay for patients with a negative CDI diagnostic result. Secondary clinical and economic outcomes were also evaluated. Independent predictors of receipt of antibiotic therapy were assessed via logistic regression. RESULTS: 141 EIA and 140 PCR patients were included. Significantly more patients were started or continued on anti-CDI antibiotic therapy after a known negative assay result in the EIA group (26 patients vs. 8 patients, P = 0.002). Duration of antibiotic therapy after a known negative result was significantly shorter in the PCR group (1 vs. 4 days, P = 0.029) and a 23% reduction in the number of tests obtained per patient was observed (1.41 ± 0.86 vs. 1.82 ± 1.35, P = 0.007). The over fourfold difference in per-test cost of the EIA assay ($8.33 vs. $42.86, P < 0.0001) was offset by the overall medication costs required for the increased treatment in the EIA group ($546.60 vs. $188.96, P = 0.191). Utilization of the EIA-based CDI assay was associated with increased odds of CDI treatment after a negative test (aOR 4.71, 95% CI 1.93-11.46, P = 0.001). CONCLUSION: The transition from an EIA to PCR-based assay for diagnosing CDI resulted in a significant decrease in the number of patients treated and the duration of treatment in response to a negative test result. This significant decrease in treatment resulted in decreased costs offsetting the utilization of a more expensive molecular test for patients with a negative CDI diagnostic result.

Clostridium difficile Infection.

Preventing Clostridium difficile, the most common cause of health care-associated infections in hospitals and infectious disease death in the United States, is a national priority. Increased rates of infection among low-risk individuals in the community call for community-based prevention efforts to halt the increasing spread of this highly contagious opportunistic infection.

A population-based matched cohort study examining the mortality and costs of patients with community-onset Clostridium difficile infection identified using emergency department visits and hospital admissions.

Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94-9.02), 3.55 (95%CI, 3.17-3.97), and 2.59 (95%CI, 2.37-2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI.

A mathematical model of Clostridium difficile transmission in medical wards and a cost-effectiveness analysis comparing different strategies for laboratory diagnosis and patient isolation.

BACKGROUND: Clostridium difficile infection (CDI) is a common and potentially fatal healthcare-associated infection. Improving diagnostic tests and infection control measures may prevent transmission. We aimed to determine, in resource-limited settings, whether it is more effective and cost-effective to allocate resources to isolation or to diagnostics. METHODS: We constructed a mathematical model of CDI transmission based on hospital data (9 medical wards, 350 beds) between March 2010 and February 2013. The model consisted of three compartments: susceptible patients, asymptomatic carriers and CDI patients. We used our model results to perform a cost-effectiveness analysis, comparing four strategies that were different combinations of 2 test methods (the two-step test and uniform PCR) and 2 infection control measures (contact isolation in multiple-bed rooms or single-bed rooms/cohorting). For each strategy, we calculated the annual cost (of CDI diagnosis and isolation) for a decrease of 1 in the average daily number of CDI patients; the strategy of the two-step test and contact isolation in multiple-bed rooms was the reference strategy. RESULTS: Our model showed that the average number of CDI patients increased exponentially as the transmission rate increased. Improving diagnosis by adopting uniform PCR assay reduced the average number of CDI cases per day per 350 beds from 9.4 to 8.5, while improving isolation by using single-bed rooms reduced the number to about 1; the latter was cost saving. CONCLUSIONS: CDI can be decreased by better isolation and more sensitive laboratory methods. From the hospital perspective, improving isolation is more cost-effective than improving diagnostics.

ECCMID 2016: addressing the burden of recurrent Clostridium difficile infections.

26th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), 9-12th April 2016, Amsterdam, The Netherlands The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) is the annual scientific meeting of the European Society of Clinical Microbiology. ECCMID 2016, held in Amsterdam, The Netherlands, was attended by over 11,600 clinical microbiologists and infectious disease physicians from more than 120 countries. The Congress offered an essential opportunity to learn more about the diagnosis, prevention and treatment of healthcare-associated infections, especially those caused by Clostridium difficile. Recurrent C. difficile infections have an especially serious adverse impact on patients, their families and healthcare systems across Europe and around the world, and continue to be a cause for concern among ECCMID delegates and their colleagues responsible for managing vulnerable patients in acute hospitals and other healthcare facilities.

High morbidity and mortality of Clostridium difficile infection and its associations with ribotype 002 in Hong Kong.

OBJECTIVES: We aim to study the disease burden, risk factors and severity of Clostridium difficile infection (CDI) in Hong Kong. METHODS: We conducted a prospective, case-control study in three acute-care hospitals in Hong Kong. Adult inpatients who developed CDI diarrhoea confirmed by PCR (n = 139) were compared with the non-CDI controls (n = 114). Ribotyping of isolates and antimicrobial susceptibility testing were performed. RESULTS: The estimated crude annual incidence of CDI was 23-33/100,000 population, and 133-207/100,000 population among those aged ≥65 years. The mean age of CDI patients was 71.5. Nursing home care, recent hospitalization, antibiotics exposure (adjusted OR 3.0, 95% CI 1.3-7.1) and proton-pump inhibitors use (adjusted OR 2.2, 95% CI 1.2-3.9) were risk factors. Severe CDI occurred in 41.7%. Overall mortality was 16.5% (among severe CDI, 26.5%). The commonest ribotypes were 002 (22.8%), 014 (14.1%), 012 and 046; ribotype 027 was absent. Ribotype 002 was associated with fluoroquinolone resistance and higher mortality (47.6% vs. 12.7%; adjusted HR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Our findings show high morbidity and mortality of CDI in the older adults, and identify ribotype 002 as a possible virulent strain causing serious infections in this cohort.

Economic evaluation of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection in Australia.

BACKGROUND AND AIM: Clostridium difficile is the most common cause of hospital-acquired diarrhea in Australia. In 2013, a randomized controlled trial demonstrated the effectiveness of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). The aim of this study is to evaluate the cost-effectiveness of fecal microbiota transplantation-via either nasoduodenal or colorectal delivery-compared with vancomycin for the treatment of recurrent CDI in Australia. METHODS: A Markov model was developed to compare the cost-effectiveness of fecal microbiota transplantation compared with standard antibiotic therapy. A literature review of clinical evidence informed the structure of the model and the choice of parameter values. Clinical effectiveness was measured in terms of quality-adjusted life years. Uncertainty in the model was explored using probabilistic sensitivity analysis. RESULTS: Both nasoduodenal and colorectal FMT resulted in improved quality of life and reduced cost compared with vancomycin. The incremental effectiveness of either FMT delivery compared with vancomycin was 1.2 (95% CI: 0.1, 2.3) quality-adjusted life years, or 1.4 (95% CI: 0.4, 2.4) life years saved. Treatment with vancomycin resulted in an increased cost of AU$4094 (95% CI: AU$26, AU$8161) compared with nasoduodenal delivery of FMT and AU$4045 (95% CI: -AU$33, AU$8124) compared with colorectal delivery. The mean difference in cost between colorectal and nasoduodenal FMT was not significant. CONCLUSIONS: If FMT, rather than vancomycin, became standard care for recurrent CDI in Australia, the estimated national healthcare savings would be over AU$4000 per treated person, with a substantial increase in quality of life.

A cost-effective anaerobic culture method & its comparison with a standard method.

Twenty six anaerobes were recovered from 150 deep-seated abscess samples cultured by the proposed two-step combustion-modified candle-jar system and Anoxomat. The degree of growth and colony size were similar in both systems, except for Clostridium difficile. The modified candle-jar system was found to be a sensitive and cost-effective alternative that might be used in resource-limited settings.

Toxicity assessment of Clostridium difficile toxins in rodent models and protection of vaccination.

Clostridium difficile is the leading cause of hospital-acquired diarrhea, also known as C. difficile associated diarrhea. The two major toxins, toxin A and toxin B are produced by most C. difficile bacteria, but some strains, such as BI/NAP1/027 isolates, produce a third toxin called binary toxin. The precise biological role of binary toxin is not clear but it has been shown to be a cytotoxin for Vero cells. We evaluated the toxicity of these toxins in mice and hamsters and found that binary toxin causes death in both animals similar to toxins A and B. Furthermore, immunization of mice with mutant toxoids of all three toxins provided protection upon challenge with native toxins. These results support the concept that binary toxin contributes to the pathogenicity of C. difficile and provide a method for monitoring the toxicity of binary toxin components in vaccines.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P = 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.

Racial Differences in Clostridium difficile Infection Rates Are Attributable to Disparities in Health Care Access.

This study confirms previously reported racial differences in Clostridium difficile infection (CDI) rates in the United States and explores the nature of those differences. We conducted a retrospective study using the 2010 Nationwide Inpatient Sample, the largest all-payer database of hospital discharges in the United States. We identified hospital stays most likely to include antibiotic treatment for infections, based on hospital discharge diagnoses, and we examined how CDI rates varied, in an attempt to distinguish between genotypic and environmental racial differences. Logistic regressions for the survey design were used to test hypotheses. Among patients likely to have received antibiotics, white patients had higher CDI rates than black, Hispanic, Asian, and Native American patients (P < 0.0001). CDI rates increased with higher income levels and were higher for hospitalizations paid by private insurance versus those paid by Medicaid or classified as self-pay or free care (P < 0.0001). Among patients admitted from skilled nursing facilities, where racial bias in health care access is less, racial differences in CDI rates disappeared (P = 1.0). Infected patients did not show racial differences in rates of complicated CDI or death (P = 1.0). Although white patients had greater CDI rates than nonwhite patients, racial differences in CDI rates disappeared in a population for which health care access was presumed to be less racially biased. This provides evidence that apparent racial differences in CDI risks may represent health care access disparities, rather than genotypic differences. CDI represents a deviation from the paradigm that increased health care access is associated with less morbidity.

The cost-benefit of federal investment in preventing Clostridium difficile infections through the use of a multifaceted infection control and antimicrobial stewardship program.

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.

In vivo assessment of SMT19969 in a hamster model of clostridium difficile infection.

SMT19969 [2,2'-bis(4-pyridyl)3H,3'-H 5,5-bibenzimidazole] is a novel narrow-spectrum nonabsorbable antibiotic currently in development for the treatment of Clostridium difficile infection. The comparative activities of SMT19969 and vancomycin against nonepidemic and epidemic strains of C. difficile were studied in an established hamster model. Against nonepidemic (VA11) strains, the survival rates of SMT19969-treated animals ranged from 80% to 95%. Vancomycin exhibited 100% protection during treatment, with relapse observed starting on day 9 and 50% survival at day 20. At 50 mg/kg of body weight, SMT19969 administered orally once daily for 5 days provided full protection of treated animals on the dosing days and through day 12 against epidemic strains. Vancomycin also protected during the dosing interval, but apparent relapse occurred earlier, starting on day 11. SMT19969 exhibited excellent in vitro activity, with MICs of 0.25 µg/ml for all isolates. The MICs for vancomycin were 2- to 4-fold higher at ≤0.5 to 1 µg/ml. All plasma sample concentrations of SMT19969 were below the limit of quantification (25 ng/ml) at all time points, consistent with the reported lack of bioavailability of the compound. Cecal concentrations were significantly above the MIC (ranging from 96 µg/ml to 172 µg/ml).

Analysis of Clostridium difficile infections after cardiac surgery: epidemiologic and economic implications from national data.

OBJECTIVES: Clostridium difficile infections (CDIs) have increased during the past 2 decades, especially among cardiac surgical patients, who share many of the comorbidity risk factors for CDI. Our objectives were to use a large national database to identify the regional-, hospital-, patient-, and procedure-level risk factors for CDI; and determine mortality, resource usage, and cost of CDIs in cardiac surgery. METHODS: Using the Nationwide Inpatient Sample database, we identified 349,122 patients who had undergone coronary artery bypass, valve, or thoracic-aortic surgery from 2004 to 2008. Of these, 2581 (0.75%) had been diagnosed with CDI. Multivariable regression analysis and the propensity method were used for risk adjustment. RESULTS: Compared with the West, CDIs were more likely to occur in the Northeast (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47) and Midwest (OR, 1.27, 95% CI, 1.11-1.46) and less likely in the South (OR, 0.80; 95% CI, 0.70-0.90). Medium-size hospitals (OR, 0.88; 95% CI, 0.78-0.99) had a lower risk of CDI than did large hospitals. Older age (>75 years; OR, 2.59; 95% CI, 1.93-3.49), longer preoperative length of stay (OR, 1.51; 95% CI, 1.43-1.60), Medicare (OR, 1.21; 95% CI, 1.05-1.39) and Medicaid (OR, 1.60; 95% CI, 1.31-1.96) coverage, and more comorbidities were associated with CDI. Among the matched pairs, patients with CDIs had greater mortality (302 [12%] vs 187 [7.2%], P<.001), a longer median length of stay (21 vs 11 days, P<.001), and greater median hospital charges ($193,330 vs $112,245, P<.001). The cumulative incremental cost of CDIs was an estimated $212 million annually. CONCLUSIONS: Our results have shown that CDI is associated with increased morbidity and resource usage. Additional work is needed to better understand the complex interplay among regional-, hospital-, and patient-level factors.