Clostridioides difficile is an opportunistic gastrointestinal pathogen capable of asymptomatic colonization and causes diseases ranging from diarrhea to pseudomembranous colitis. Accurate diagnosis of C. difficile infection (CDI) is challenging and critical for treatment and control. We hypothesized that gut microbiome profiles could help distinguish C. difficile colonized patients with diarrhea from those with true CDI. We analyzed 172 stool samples from individuals who tested glutamate dehydrogenase positive for C. difficile. Participants were categorized by toxin status (i.e., toxin positive or negative) and then further classified into three toxin groups based on the production of toxin, and if not produced, whether the C. difficile strain carried toxin-encoding genes. We examined associations between patient characteristics, prior antibiotics exposure, microbiome community structure and function, and toxin categories. Thirty-five percent of toxin-negative participants received antibiotics despite not meeting the criteria for true CDI. Enterococcus species were abundant in all groups. The relative abundance of E. faecalis was higher among individuals with prior antibiotics exposure. Alpha and beta diversity did not differ by toxin group. After controlling for prior antibiotics exposure and previous CDI episode, the abundance of Akkermansia muciniphila, Flavonifractor plautii, and Bifidobacterium adolescentis distinguished individuals with toxin-positive C. difficile. C. difficile abundance did not differentiate participants with true CDI from those who were colonized. We identified associations between the gut microbiome and C. difficile toxin gene presence and toxin production. These results highlight the potential for microbiome-informed diagnostics to improve CDI accuracy and guide treatment decisions.IMPORTANCEClostridioides difficile colonizes humans and causes diarrhea in community and hospital settings. C. difficile infection (CDI) is a toxin-mediated disease, and its diagnosis is challenging. The goal of this study was to determine whether differences in the gut microbiome could help distinguish between colonized individuals and those with CDI. We examined stool samples and data from 172 individuals categorized into three groups based on the detection of toxin and, if not detected, whether toxin-encoding genes were present in the C. difficile strain. We identified bacteria, such as Enterococcus faecalis, that were more abundant in people who had used antibiotics. While the diversity of the gut microbiome did not differ by toxin group, specific gut bacteria, antibiotic resistance genes, and metabolic pathways were associated with toxin group. Our findings suggest that considering the full gut microbiome and factors like past antibiotic use could help improve the diagnosis and treatment of CDI.

Abstract Background Recent advancements in treating Clostridioides difficile infection (CDI) include therapeutics to prevent further recurrence in patients with recurrent CDI (rCDI). However, little is known about which patients are at increased risk for multiple recurrences (≥ 2 rCDI). We sought to identify predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI). Methods The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts population-based CDI surveillance in 10 U.S. sites. We defined iCDI as a positive C. difficile test during January 2018–August 2019 in a person aged ≥ 18 years with no prior positive test reported to EIP. rCDI was defined as a positive test ≥ 14 days from the previous positive test within 180 days after iCDI. All patients with community-onset iCDI and a random sample of patients with healthcare-facility onset iCDI (i.e., hospital-onset, long-term care facility onset) had full chart reviews. Multiple imputation was performed on missing race/ethnicity. Candidate variables determined a priori to be potentially associated with mrCDI were entered into an initial multivariable logistic regression model. Patients without mrCDI who died within 180 days of their iCDI were excluded from the model. Candidate variables with a p-value < 0.1 in the initial model were included in the final model. Results Of 18,829 patients with iCDI, 882 (4.7%) had mrCDI, ranging from 2 to 5 rCDI per patient in the 180 days following iCDI. Median time between each rCDI was 43 days (interquartile range: 27–65 days). Full charts were reviewed for 435 iCDI patients with mrCDI and 7474 iCDI patients without mrCDI. Characteristics of patients with and without mrCDI are shown in Table 1. In multivariable analysis, age ≥ 65 years, recent hospitalization, chronic hemodialysis, and recent nitrofurantoin use were significantly associated with mrCDI (Table 2). Conclusion Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use may be at increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings would aid in clinical decision making. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support

OBJECTIVE:Patients tested for Clostridioides difficile infection (CDI) using a 2-step algorithm with a nucleic acid amplification test (NAAT) followed by toxin assay are not reported to the National Healthcare Safety Network as a laboratory-identified CDI event if they are NAAT positive (+)/toxin negative (-). We compared NAAT+/toxin- and NAAT+/toxin+ patients and identified factors associated with CDI treatment among NAAT+/toxin- patients. DESIGN:Retrospective observational study. SETTING:The study was conducted across 36 laboratories at 5 Emerging Infections Program sites. PATIENTS:We defined a CDI case as a positive test detected by this 2-step algorithm during 2018-2020 in a patient aged ≥1 year with no positive test in the previous 8 weeks. METHODS:We used multivariable logistic regression to compare CDI-related complications and recurrence between NAAT+/toxin- and NAAT+/toxin+ cases. We used a mixed-effects logistic model to identify factors associated with treatment in NAAT+/toxin- cases. RESULTS:Of 1,801 cases, 1,252 were NAAT+/toxin-, and 549 were NAAT+/toxin+. CDI treatment was given to 866 (71.5%) of 1,212 NAAT+/toxin- cases versus 510 (95.9%) of 532 NAAT+/toxin+ cases (P < .0001). NAAT+/toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.65; 95% CI, 0.55-0.77) but not CDI-related complications (aOR, 1.05; 95% CI, 0.87-1.28). Among NAAT+/toxin- cases, white blood cell count ≥15,000/µL (aOR, 1.87; 95% CI, 1.28-2.74), ≥3 unformed stools for ≥1 day (aOR, 1.90; 95% CI, 1.40-2.59), and diagnosis by a laboratory that provided no or neutral interpretive comments (aOR, 3.23; 95% CI, 2.23-4.68) were predictors of CDI treatment. CONCLUSION:Use of this 2-step algorithm likely results in underreporting of some NAAT+/toxin- cases with clinically relevant CDI. Disease severity and laboratory interpretive comments influence treatment decisions for NAAT+/toxin- cases.

Background: Medicare claims are frequently used to study Clostridioides difficile infection (CDI) epidemiology. Categorizing CDI based on location of onset and potential exposure is critical in understanding transmission patterns and prevention strategies. While claims data are well-suited for identifying prior healthcare utilization exposures, they lack specimen collection and diagnosis dates to assign likely location of onset. Algorithms to classify CDI onset and healthcare association using claims data have been published, but the degree of misclassification is unknown. Methods: We linked patients with laboratory-confirmed CDI reported to four Emerging Infections Program (EIP) sites from 2016-2020 to Medicare beneficiaries using residence, birth date, sex, and hospitalization and/or healthcare exposure dates. Uniquely linked patients with fee-for-service Medicare A/B coverage and complete EIP case report forms were included. Patients with a claims CDI diagnosis code within ±28 days of a positive CDI test reported to EIP were categorized as hospital-onset (HO), long-term care facility onset (LTCFO), or community-onset (CO, either healthcare facility-associated [COHCFA] or community-associated [CA]) using a previously published algorithm based on claim type, ICD-10-CM code position, and duration of hospitalization (if applicable). EIP classifies CDI into these categories using positive specimen collection date and other information from chart review (e.g. admit/discharge dates). We assessed concordance of EIP and claims case classifications using Cohen’s kappa. Results: Of 10,002 eligible EIP-identified CDI cases, 7,064 were linked to a unique beneficiary; 3,451 met Medicare A/B fee-for-service coverage inclusion criteria. Of these, 650 (19%) did not have a claims diagnosis code ±28 days of the EIP specimen collection date (Table); 48% (313/650) of those without a claims diagnosis code were categorized by EIP as CA CDI. Among those with a CDI diagnosis code, concurrence of claims-based and EIP CDI classification was 68% (κ=0.56). Concurrence was highest for HO and lowest for COHCFA CDI. A substantial number of EIP-classified CO CDIs (30%, Figure) were misclassified as HO using the claims-based algorithm; half of these had a primary ICD-10 diagnosis code of sepsis (226/454; 50%). Conclusions: Evidence of CDI in claims data was found for 81% of EIP-reported CDI cases. Medicare classification algorithms concurred with the EIP classification in 68% of cases. Discordance was most common for community-onset CDI patients, many of whom were hospitalized with a primary diagnosis of sepsis. Misclassification of CO-CDI as HO may bias findings of claims-based CDI studies.

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Recurrent Clostridioides difficile infection (RCDI) causes an increased burden on the healthcare system. We calculated RCDI incidence and identified factors associated with RCDI cases in New Haven County, Connecticut, USA, during 2015-2020 by using data from population-based laboratory surveillance. A subset of C. difficile cases had complete chart reviews conducted for RCDI and potentially associated variables. RCDI was defined as a positive C. difficile specimen occurring 2-8 weeks after incident C. difficile infection. We compared cases with and without RCDI by using multiple regression. RCDI occurred in 12.0% of 4,301 chart-reviewed C. difficile cases, showing a U-shaped time trend with a sharp increase in 2020, mostly because of an increase in hospital-onset cases. Malignancy (odds ratio 1.51 [95% CI 1.11-2.07]) and antecedent nitrofurantoin use (odds ratio 2.37 [95% CI 1.23-4.58]) were medical risk factors for RCDI. The 2020 increase may reflect the impact of the COVID-19 pandemic.

Shiga toxin–producing Escherichia coli (STEC) causes acute diarrheal illness. To determine risk factors for non-O157 STEC infection, we enrolled 939 patients and 2,464 healthy controls in a case–control study conducted in 10 US sites. The highest population-attributable fractions for domestically acquired infections were for eating lettuce (39%), tomatoes (21%), or at a fast-food restaurant (23%). Exposures with 10%–19% population attributable fractions included eating at a table service restaurant, eating watermelon, eating chicken, pork, beef, or iceberg lettuce prepared in a restaurant, eating exotic fruit, taking acid-reducing medication, and living or working on or visiting a farm. Significant exposures with high individual-level risk (odds ratio >10) among those >1 year of age who did not travel internationally were all from farm animal environments. To markedly decrease the number of STEC-related illnesses, prevention measures should focus on decreasing contamination of produce and improving the safety of foods prepared in restaurants.

Abstract Background U.S. laboratories are increasingly using a two-step algorithm to diagnose Clostridioides difficile infection (CDI) that starts with a nucleic acid amplification test (NAAT), and if positive, reflexes to a toxin enzyme immunoassay. Here only a NAAT+/toxin+ result is reported to the Centers for Disease Control and Prevention’s (CDC) National Healthcare Safety Network (NHSN) as a CDI laboratory-identified (LabID) event, but limited data suggest that NAAT+/toxin- results may also be considered CDI by clinicians. To explore this discrepancy, we compared the characteristics and treatment of NAAT+/toxin- and NAAT+/toxin+ patients. Methods CDC’s Emerging Infections Program (EIP) conducts population-based CDI surveillance. A case was defined as a positive C. difficile test in a person aged ≥1 year with no positive tests in the prior 8 weeks. We included cases detected by this two-step algorithm in 5 EIP sites during 2018–2020 that underwent a full chart review. Multivariable logistic regression models adjusting for age, sex, race, comorbidities, epidemiologic classification, and CDI therapy were used to compare CDI-related complications (i.e., toxic megacolon, ileus, colectomy, or intensive-care unit stay) and recurrence between the two groups. Results Of 1250 NAAT+ cases, 897 (72%) were toxin- and 353 (28%) were toxin+. Lower percentages of toxin- versus toxin+ cases were aged ≥65 years (42% vs 58%; P< 0.0001), had diarrhea (779/831 [94%] vs 329/338 [97%]; P=0.01), or had white blood cell counts ≥15,000 cells/μL (183/811 [23%] vs 132/321 [42%]; P< 0.0001). CDI therapy was given to 683/882 (77%) toxin- versus 338/349 (97%) toxin+ cases (P< 0.0001). In multivariable analysis, toxin- status was protective for recurrence (adjusted odds ratio [aOR], 0.49; 95% confidence interval [CI], 0.32–0.74) but not for CDI-related complications (aOR, 1.00; 95% CI, 0.64–1.56). Conclusion NAAT+/toxin- cases were less likely to have recurrence but were as likely to have CDI-related complications as NAAT+/toxin+ cases. More than twice as many potentially unreported NAAT+/toxin- cases were treated than the number of reported NAAT+/toxin+ treated cases. Use of this two-step algorithm likely results in underreporting of treated CDI cases to NHSN. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support Dale N. Gerding, MD, Destiny Pharma plc.: Advisor/Consultant.

Among persons with an initial Clostridioides difficile infection (CDI) across 10 US sites in 2018 compared with 2013, 18.3% versus 21.1% had ≥1 recurrent CDI (rCDI) within 180 days. We observed a 16% lower adjusted risk of rCDI in 2018 versus 2013 (P < .0001).

Abstract Background Interventions to reduce community-onset (CO) Clostridioides difficile Infection (CDI) are not usually hospital-based due to the perception that they are often acquired outside the hospital. We determined the proportion of admitted CO CDI that might be associated with previous hospitalization. Methods The CDC’s Emerging Infections Program conducts population-based CDI surveillance in 10 US sites. We defined an incident case as a C. difficile-positive stool collected in 2017 from a person aged ≥ 1 year admitted to a hospital with no positive tests in the prior 8 weeks. Cases were defined as CO if stool was collected within 3 days of hospitalization. CO cases were classified into four categories: long-term care facility (LTCF)-onset if patient was admitted from an LTCF; long-term acute care hospital (LTACH)-onset if patient was admitted from an LTACH; CO-healthcare-facility associated (CO-HCFA) if patient was admitted from a private residence but had a prior healthcare-facility admission in the past 12 weeks; or community-associated (CA) if there was no admission to a healthcare facility in the prior 12 weeks. We excluded hospitals with < 10 cases among admitted catchment-area residents. Results Of 4724 cases in 86 hospitals, 2984 (63.2%) were CO (median per hospital: 65.8%; interquartile range [IQR]: 58.3%-70.7%). Among the CO cases, 1424 (47.7%) were CA (median per hospital: 48.1%; IQR: 40.3%-57.7%), 1201 (40.3%) were CO-HCFA (median per hospital: 41.0%; IQR: 32.9%-47.8%), 350 (11.7%) were LTCF-onset (median per hospital: 10.0%; IQR: 0.6%-14.4%), and 9 (0.3%) were LTACH-onset. Of 1201 CO-HCFA cases, 1174 (97.8%) had a prior hospitalization; among these, 978 (83.3%) (median per hospital: 83.3%; IQR: 69.2%-90.6%), which consists of 32.8% of all hospitalized CO cases, had been discharged from the same hospital (Figure), and 84.4% of the 978 cases (median per hospital: 88.2%: IQR: 76.5%-100.0%) had received antibiotics sometime in the prior 12 weeks. Figure. Frequency of Cases Discharged in the 12 Weeks Prior to Readmission with Clostridioides difficile Infection (N=1138*) Conclusion A third of hospitalized CO CDI had been recently discharged from the same hospital, and most had received antibiotics during or soon after the last admission. Hospital-based and post-discharge antibiotic stewardship interventions could help reduce subsequent CDI hospitalizations. Disclosures Ghinwa Dumyati, MD, Roche Diagnostics (Consultant)

Abstract Background Treatment guidelines for Clostridioides difficile infection (CDI) were updated by the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) in 2017, notably for disease severity and antibiotic recommendations. Our objectives were to assess Connecticut medical providers’ concordance (2017-2019) with the 2017 update. The effect of guideline concordance on the risk of CDI recurrence was also assessed. Methods Using data from the Connecticut Emerging Infections Program’s CDI surveillance in New Haven County, severity and concordance were defined. For severity, white blood cell count and presence of megacolon and/or ileus were used. Concordant treatment was defined as receiving the recommended first-line antibiotic (vancomycin for adult patients, vancomycin or metronidazole for pediatric patients) for exactly 10 days. In univariate & multivariate analyses, significance was determined by a p-value of < 0.05. Results Of 1,216 cases, concordance increased from 10.0% in 2017 to 36.9% in 2019. Concordance with first-line antibiotic increased from 40.2% in 2017 to 80.8% in 2019. Concordance was highest for fulminant cases (62.2%). The recurrence rate was 11.2% and highest for non-severe cases and older cases but was not significantly associated with concordance. Concordance with selected treatment criteria by year, 2017-2019 Conclusion From 2017 through 2019, CDI treatment in New Haven County increasingly was concordant with the updated 2017 IDSA/SHEA guidelines, but still low overall in 2019. Although concordance with treatment did not affect recurrence risk, close attention should be paid by medical providers to non-severe cases and older cases as they are at an increased risk for recurrence. Disclosures All Authors: No reported disclosures

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.).

AbstractObjectives:To assess Connecticut medical providers’ concordance (2018–2019) with the 2017 Clostridioides difficile infection (CDI) treatment update by the Infectious Disease Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). The effect of guideline concordance on CDI recurrence risk was also assessed.Design:Prospective, population-based study.Setting:New Haven County, Connecticut, from January 1, 2017, to December 31, 2019.Patients:CDI incident case (no positive tests in the prior 8 weeks), not limited by care setting.Methods:Using data from the Emerging Infections Program’s CDI surveillance, severity and concordance were defined. Presence of megacolon and/or ileus defined fulminant disease; absence defined nonsevere/severe disease. Using 2017 treatment as baseline, 2018–2019 concordance was defined as receiving the recommended first-line antibiotic (ie, vancomycin or fidaxomicin for adult patients, vancomycin or metronidazole for pediatric patients) for exactly 10 days. For all analyses, significance was P < .05.Results:Among 990 cases, concordance increased from 24.8% in 2018 to 37.0% in 2019. First-line antibiotic concordance increased from 61.2% in 2018 to 79.9% in 2019. Recurrence risk was significantly associated with patients aged ≥65 years and was highest for those aged 75–84 years, but this factor was not significantly associated with concordance.Conclusions:From 2018 through 2019, CDI treatment in New Haven County increasingly was concordant with the 2017 treatment update but remained low in 2019. Although concordance with treatment guidelines did not affect recurrence risk, close attention should be paid by medical providers to patients aged ≥65 years, specifically those aged 75–84 years because they are at an increased risk for recurrence.

Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines describe recommended therapy for Clostridioides difficile infection (CDI). To describe CDI treatment and, among those with severe CDI, determine predictors of adherence to the 2010 IDSA/SHEA treatment guidelines. We analyzed 2013–2015 CDI treatment data collected through the Centers for Disease Control and Prevention’s Emerging Infections Program. Generalized linear mixed models were used to identify predictors of guideline-adherent therapy. A CDI case was defined as a positive stool specimen in a person aged ≥ 18 years without a positive test in the prior 8 weeks; severe CDI cases were defined as having a white blood cell count ≥ 15,000 cells/μl. Prescribing and predictors of guideline-adherent CDI therapy for severe disease. Of 18,243 cases, 14,257 (78%) were treated with metronidazole, 7683 (42%) with vancomycin, and 313 (2%) with fidaxomicin. The median duration of therapy was 14 (interquartile range, 11–15) days. Severe CDI was identified in 3250 (18%) cases; of 3121 with treatment data available, 1480 (47%) were prescribed guideline-adherent therapy. Among severe CDI cases, hospital admission (adjusted odds ratio [aOR] 2.48; 95% confidence interval [CI] 1.90, 3.24), age ≥ 65 years (aOR 1.37; 95% CI 1.10, 1.71), Charlson comorbidity index ≥ 3 (aOR 1.27; 95% CI 1.04, 1.55), immunosuppressive therapy (aOR 1.21; 95% CI 1.02, 1.42), and inflammatory bowel disease (aOR 1.56; 95% CI 1.13, 2.17) were associated with being prescribed guideline-adherent therapy. Provider adherence to the 2010 treatment guidelines for severe CDI was low. Although the updated 2017 CDI guidelines, which expand the use of oral vancomycin for all CDI, might improve adherence by removing the need to apply severity criteria, other efforts to improve adherence are likely needed, including educating providers and addressing barriers to prescribing guideline-adherent therapy, particularly in outpatient settings.

Abstract Background Despite overall progress in preventing Clostridioides difficile Infection (CDI), community-associated (CA) infections have been steadily increasing. Although the incubation period of CDI is thought to be relatively short, gastrointestinal microbial disruption from remote healthcare exposures (e.g., inpatient antibiotic use) may be associated with CA-CDI. To assess this potential association, we linked CA-CDI infections identified through CDC’s Emerging Infections Program (EIP) to Medicare claims data to describe prior healthcare utilization. Methods We defined an EIP CA-CDI case as a positive C. difficile test collected in 2014–2015 from an outpatient or inpatient within 3 days of hospital admission, provided there was no positive test in the prior 8 weeks and no admission to a healthcare facility in the prior 12 weeks. We linked EIP CA-CDI cases aged ≥65 years to a Medicare beneficiary using unique combinations of birthdate, sex, and zip code. Cases were included if they maintained continuous fee-for-service coverage for 1 year prior to the event date. To calculate exposure odds ratios for previous hospitalizations, each case was matched to 5 control beneficiaries on age, sex, and county of residence. We used logistic regression to calculate adjusted matched odds ratios (amOR) that controlled for chronic conditions. Results We successfully linked 2,287/3,367 (68%) EIP CA-CDI cases. Of these, 1,236 cases met inclusion criteria; the median age was 77 years and 63% were female. We identified 69 (5.6%) cases with misclassification of prior healthcare exposures, most of whom (48, 70%) were hospitalized in the 12 weeks prior to their event. Among the 1,167 true CA-CDI cases, 33% were hospitalized in the prior 12 weeks to 1 year. The median number of weeks from prior hospitalization to CDI was 27 (IQR 18–38, Figure 1). Cases had a higher risk of hospitalization than matched controls in the prior 3–6 months (amOR: 2.33, 95% CI: 1.87, 2.90) and 6–12 months (amOR: 1.43 95% CI: 1.18, 1.74). Conclusion Remote hospitalization in the previous year was a significant risk factor for CA-CDI, especially in the 3–6 months prior to CA-CDI. Long-lasting prevention strategies implemented at hospital discharge and enhanced inpatient antibiotic stewardship may prevent CA-CDI among older adults. Disclosures All Authors: No reported Disclosures.

Clostridium difficile infection (CDI) is a common healthcare-associated infection, particularly among older adults. We used laboratory-confirmed CDI surveillance data from 8 states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program linked to claims data for Centers for Medicare and Medicaid Services (CMS) beneficiaries to measure variation in 1-year outcomes associated with CDI. A CDI case was defined as a positive C. difficile stool test in 2014 in a person without a positive test in the prior 8 weeks. Cases aged ≥65 years were linked to their CMS beneficiary ID using unique combinations of date of birth, sex, and zip code. Each case was matched to five control beneficiaries who did not link to any case and were residents of the same catchment area. Inclusion criteria were continuous fee-for-service Medicare for the entire study period (1 year before and after event date), and no hospitalization or skilled nursing facility stay with an ICD-9-CM code for CDI in the year prior to their match date. Multivariable logistic regression models were used to compare mortality and hospitalization for 1 year following the event date between beneficiaries with and without CDI, adjusting for age, sex, race, catchment area, chronic conditions, number of hospitalizations in the prior year, and hospitalization status at the time of and 7 days preceding the event date. Of 5,097 cases aged ≥65, 3,082 (60%) were linked to a CMS ID, and 1,832 (59%) met inclusion criteria. In crude analysis, 34% of beneficiaries with CDI died within 1 year, compared with 5% of beneficiaries without CDI. Beneficiaries with CDI were also more likely to be hospitalized in the subsequent year (54% vs. 17%). Beneficiaries with CDI had a higher adjusted odds of death (adjusted OR 3.01, 95% CI: 2.46, 3.69) and hospitalization within 1 year (adjusted OR 1.93, 95% CI: 1.65, 2.25) than those without CDI. Older adults with CDI were three times more likely to die in the year following infection and nearly two times more likely to be hospitalized compared with those without CDI, revealing independent long-term risk of poor outcomes. This excess morbidity and mortality supports the need to develop novel CDI prevention strategies for this population. All authors: No reported disclosures.

Abstract Background An increasing proportion of Clostridium difficile infections (CDI) in the United States are community-associated (CA). We conducted a case-control study to identify CA-CDI risk factors. Methods We enrolled participants from 10 US sites during October 2014–March 2015. Case patients were defined as persons age ≥18 years with a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization who had no admission to a health care facility in the prior 12 weeks and no prior CDI diagnosis. Each case patient was matched to one control (persons without CDI). Participants were interviewed about relevant exposures; multivariate conditional logistic regression was performed. Results Of 226 pairs, 70.4% were female and 52.2% were ≥60 years old. More case patients than controls had prior outpatient health care (82.1% vs 57.9%; P < .0001) and antibiotic (62.2% vs 10.3%; P < .0001) exposures. In multivariate analysis, antibiotic exposure—that is, cephalosporin (adjusted matched odds ratio [AmOR], 19.02; 95% CI, 1.13–321.39), clindamycin (AmOR, 35.31; 95% CI, 4.01–311.14), fluoroquinolone (AmOR, 30.71; 95% CI, 2.77–340.05) and beta-lactam and/or beta-lactamase inhibitor combination (AmOR, 9.87; 95% CI, 2.76–340.05),—emergency department visit (AmOR, 17.37; 95% CI, 1.99–151.22), white race (AmOR 7.67; 95% CI, 2.34–25.20), cardiac disease (AmOR, 4.87; 95% CI, 1.20–19.80), chronic kidney disease (AmOR, 12.12; 95% CI, 1.24–118.89), and inflammatory bowel disease (AmOR, 5.13; 95% CI, 1.27–20.79) were associated with CA-CDI. Conclusions Antibiotics remain an important risk factor for CA-CDI, underscoring the importance of appropriate outpatient prescribing. Emergency departments might be an environmental source of CDI; further investigation of their contribution to CDI transmission is needed.