Background:Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized. Methods:Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors. Results:Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05). Conclusions:Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.

During 2011-2015, the adjusted long-term-care facility onset Clostridium difficile infection incidence rate in persons aged ≥65 years decreased annually by 17.45% (95% confidence interval, 14.53%-20.43%) across 10 US sites. A concomitant decline in inpatient fluoroquinolone use and the C difficile epidemic strain NAP1/027 among persons aged ≥65 years may have contributed to the decrease in long-term-care facility-onset C difficile infection incidence rate.

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.

Abstract Background Traditionally a hospital-acquired pathogen, Clostridium difficile is increasingly recognized as an important cause of diarrhea in community settings. Health disparities in C. difficileinfection (CDI) have been reported, but little is known about the social determinants of health that influence community-associated (CA) CDI incidence. We sought to identify socioeconomic status (SES) factors associated with increased CA-CDI incidence. Methods Population-based CDI surveillance is conducted in 35 U.S. counties through the Centers for Disease Control and Prevention’s Emerging Infections Program. A CA-CDI case is defined as a positive C. difficile stool specimen collected as an outpatient or within three days of hospitalization in a person aged ≥ 1 year who did not have a positive test in the prior 8 weeks or an overnight stay in a healthcare facility in the prior 12 weeks. ArcGIS software was used to geocode 2014–2015 CA-CDI case addresses to a 2010 census tract (CT). Incidence rate was calculated using 2010 Census population denominators. CT-level SES factors were obtained from the 2011–2015 American Community Survey 5-year estimates and divided into deciles. To account for CT-level clustering effects, separate generalized linear mixed models with negative binomial distribution were used to evaluate the association between each SES factor and CA-CDI incidence, adjusted by age, sex and race. Results Of 9686 CA-CDI cases, 9417 (97%) had addresses geocoded to a CT; of these, 62% were female, 82% were white, and 35% were aged ≥65 years. Annual CA-CDI incidence was 42.9 per 100,000 persons. After adjusting for age, sex and race, CT-level SES factors significantly associated with increased CA-CDI incidence included living under the poverty level (rate ratio [RR] 1.12; 95% confidence interval [CI] 1.09–1.53), crowding in homes (RR 1.11; 95% CI 1.01–1.21), low education (RR 1.11; 95% CI 1.07–1.15), low income (RR 1.15; 95% CI 1.12–1.17), having public health insurance (RR 1.21; 95% CI 1.18–1.24), receiving public assistance income (RR 1.69; 95% CI 1.55–1.84), and unemployment (RR 1.14; 95% CI 1.07–1.22). Conclusion Areas with lower SES have modestly increased CA-CDI incidence. Understanding the mechanisms by which SES factors impact CA-CDI incidence could help guide prevention efforts in these higher-risk areas. Disclosures All authors: No reported disclosures.

1Emory University School of Medicine, Department of Medicine, Atlanta, GA. 2Atlanta Veterans Affairs Medical Center, Atlanta, GA. 3Georgia Emerging Infections Program, Atlanta, GA. 4Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Healthcare Quality Promotion, Atlanta, GA. 5Oregon Health Authority, Public Health Division, Portland, OR. 6Tennessee Department of Health, Nashville, TN. 7University of Rochester Medical Center, Rochester, NY. 8Minnesota Department of Health, St. Paul, MN. 9Colorado Department of Public Health and Environment, Denver, CO. 10Ya le School of Public Health, Connecticut Emerging Infections Program, New Haven, CT. 11University of New Mexico, New Mexico Emerging Infections Program, Albuquerque, NM. 12Maryland Department of Health and Mental Hygiene, Baltimore, MD. 13Department of Medicine, University of Ca lifornia, San Francisco, School of Medicine, San Francisco, CA. 14Department of Medicine, Loyola University Chicago Stritch School of Medicine, Maywood, IL. 15Edward Hines, Jr., Veterans Affairs Hospital, Hines, IL

BACKGROUND Studies are conflicting regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. METHODS CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15 000 cells/µL within 1 day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. RESULTS Strain typing results were available for 2057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%), and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [AOR], 1.74; 95% confidence interval [CI], 1.36-2.22), severe outcome (AOR, 1.66; 95% CI, 1.09-2.54), and death within 14 days (AOR, 2.12; 95% CI, 1.22-3.68). CONCLUSIONS NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.

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.

ABSTRACT We describe the adoption of nucleic acid amplification tests (NAAT) for Clostridium difficile diagnosis and their impact on stool rejection policies and C. difficile positivity rates. Of the laboratories with complete surveys, 51 (43%) reported using NAAT in 2011. Laboratories using NAAT had stricter rejection policies and increased positivity rates.

Accurate information about deaths is important when determining the human health and economic burden of foodborne diseases. We reviewed death certificate data to assess the accuracy of deaths reported to the Foodborne Diseases Active Surveillance Network (FoodNet). Data were highly accurate, and few deaths were missed through active surveillance.