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Background The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts active laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE), extended spectrum beta-lactamase-producing Enterobacterales (ESBL-E), and carbapenem-resistant Acinetobacter baumannii (CRAB) in 10 U.S. sites. To describe the impact of the COVID-19 pandemic on the epidemiology of these antibiotic-resistant gram-negative bacteria (AR-GNB), we assessed characteristics of AR-GNB patients with and without a prior SARS-CoV-2 positive (SC2+) viral test. Methods In 2020 among EIP catchment-area residents, an incident CRAB or CRE case was defined as the first isolation of A. baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes, K. oxytoca, K. pneumonia, or K. variicola in a 30-day period resistant to ≥1 carbapenem (excluding ertapenem for CRAB) from a normally sterile site or urine. An incident ESBL-E case was defined as the first isolation of E. coli, K. pneumonia, or K. oxytoca in a 30-day period resistant to any third-generation cephalosporin and non-resistant to all carbapenems from a normally sterile site or urine. Patient charts were reviewed. Results Of 3904 AR-GNB cases with data available, 163 (4%) had a prior SC2+ test (85 ESBL-E, 70 CRE, and 8 CRAB). Median time from the most recent SC2+ test to AR-GNB culture date was 20 days (IQR 1–48 days). AR-GNB cases with a SC2+ test versus those without were more likely to be Black, non-Hispanic than another race/ethnicity (31% vs 15%; P< 0.0001), aged ≥65 years (62% vs 52%; P=0.0139), and to have prior healthcare exposures (63% vs 49%; P=0.0003) and indwelling devices (51% vs 28%; P< 0.0001). They were also more likely to have bacteremia (24% vs 11%; P< 0.0001), pneumonia (6% vs 1%; P< 0.0001) and be hospitalized around the time of their AR-GNB culture (67% vs 36%; P< 0.0001); median time from SC2+ test to hospital admission was 0.5 day (IQR 0–29.5 days). Conclusion AR-GNB infections preceded by a SC2+ test were rare but more severe and associated with more healthcare risk factors. This underscores the need for continued infection prevention and control practices and monitoring of these infections during the COVID-19 pandemic. Disclosures Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

Background Studies describing risk factors for Clostridioides difficile infection (CDI) are often limited in their ability to identify potentially important exposures occurring long before diagnosis. We describe hospitalizations and antibiotic use (AU) occurring up to one year prior to CDI diagnosis among Medicare beneficiaries. Methods We studied incident CDI cases (positive C. difficile test in a person ≥65 years without a positive test in the prior 8 weeks) identified during 2016–2018 through population-based CDI surveillance from four states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program. The analysis included specimens collected in all settings and was limited to case patients who were identified as having fee-for-service Medicare and Part D drug coverage for the year preceding specimen collection. Inpatient hospitalization data was extracted from Medicare Provider Analysis and Review (MEDPAR) files and outpatient AU (prescriptions filled) was determined using Part D drug event files. Timing of hospitalizations and antibiotic prescriptions were described as recent (0–3 months prior to specimen collection) or remote (4–12 months prior). Results Of 1,953 CDI cases, 1,594 (82%) filled ≥1 course of outpatient antibiotics in the prior year; 805 (41%) filled an antibiotic both recently and remotely, 497 (25%) only remotely, and 292 (15%) only recently. Cases with outpatient AU received a median of 23.5 (IQR 12–46) total days supplied, and a median of 2 different antibiotic classes (IQR 1 – 3). The most frequent antibiotic classes filled include fluoroquinolones (17% of all antibiotics filled), 1st generation cephalosporins (10%), and folate pathway inhibitors (10%). Overall, 1,314 (67%) cases were hospitalized in the prior year; 569 (29%) were hospitalized both recently and remotely, 446 (23%) only recently, and 299 (15%) only remotely. Median length of stay was 13 days (IQR 6–28). A total of 142 cases (7%) did not have hospitalization or outpatient AU in the prior year, and 1,097 (56%) had both. Conclusion Incident CDI cases have substantial exposure to recent and remote hospitalization and outpatient AU. Understanding cumulative effects of multiple risk factors can guide prevention strategies, including antibiotic stewardship efforts. Disclosures Scott Fridkin, MD, Pfizer: Grant/Research Support Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

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.

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Janssen COVID-19 (Ad.26.COV2.S) vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson; New Brunswick, New Jersey), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for its use in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of the Janssen COVID-19 vaccine after reports of six U.S. cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare thromboembolic syndrome, among Janssen COVID-19 vaccine recipients (3). Two emergency ACIP meetings were rapidly convened to review reported cases of thrombosis with thrombocytopenia syndrome (TTS) and to consider updated recommendations for use of the Janssen COVID-19 vaccine in the United States. On April 23, 2021, after a discussion of the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged ≥18 years under the FDA's EUA, which now includes a warning that rare clotting events might occur after vaccination, primarily among women aged 18-49 years. Patient and provider education about the risk for TTS with the Janssen COVID-19 vaccine, especially among women aged

Background:Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.Methods:We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.Results:Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.Conclusions:Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.

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 bu...

Background The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission. Methods Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA. Results Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review. Conclusions The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission.

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.

Background: The NHSN has used positive laboratory tests for surveillance of Clostridioides difficile infection (CDI) LabID events since 2009. Typically, CDIs are detected using enzyme immunoassays (EIAs), nucleic acid amplification tests (NAATs), or various test combinations. The NHSN uses a risk-adjusted, standardized infection ratio (SIR) to assess healthcare facility-onset (HO) CDI. Despite including test type in the risk adjustment, some hospital personnel and other stakeholders are concerned that NAAT use is associated with higher SIRs than are EIAs. To investigate this issue, we analyzed NHSN data from acute-care hospitals for July 1, 2017 through June 30, 2018. Methods: Calendar quarters for which CDI test type was reported as NAAT (includes NAAT, glutamate dehydrogenase (GDH)+NAAT and GDH+EIA followed by NAAT if discrepant) or EIA (includes EIA and GDH+EIA) were selected. HO CDI SIRs were calculated for facility-wide inpatient locations. We conducted the following analyses: (1) Among hospitals that did not switch their test type, we compared the distribution of HO incident rates and SIRs by those reporting NAAT vs EIA. (2) Among hospitals that switched their test type, we selected quarters with a stable switch pattern of 2 consecutive quarters of each of EIA and NAAT (categorized as pattern EIA-to-NAAT or NAAT-to-EIA). Pooled semiannual SIRs for EIA and NAAT were calculated, and a paired t test was used to evaluate the difference of SIRs by switch pattern. Results: Most hospitals did not switch test types (3,242, 89%), and 2,872 (89%) reported sufficient data to calculate SIRs, with 2,444 (85%) using NAAT. The crude pooled HO CDI incidence rates for hospitals using EIA clustered at the lower end of the histogram versus rates for NAAT (Fig. 1). The SIR distributions of both NAAT and EIA overlapped substantially and covered a similar range of SIR values (Fig. 1). Among hospitals with a switch pattern, hospitals were equally likely to have an increase or decrease in their SIR (Fig. 2). The mean SIR difference for the 42 hospitals switching from EIA to NAAT was 0.048 (95% CI, −0.189 to 0.284; P = .688). The mean SIR difference for the 26 hospitals switching from NAAT to EIA was 0.162 (95% CI, −0.048 to 0.371; P = .124). Conclusions: The pattern of SIR distributions of both NAAT and EIA substantiate the soundness of NHSN risk adjustment for CDI test types. Switching test type did not produce a consistent directional pattern in SIR that was statistically significant.Disclosures: NoneFunding: None

Background: The National Healthcare Safety Network (NHSN) has used positive laboratory tests for surveillance of Clostridioides difficile infection (CDI) LabID events since 2009. Typically, CDIs are detected using enzyme immunoassays (EIAs), nucleic acid amplification tests (NAATs), or various test combinations. The NHSN uses a risk-adjusted, standardized infection ratio (SIR) to assess healthcare facility-onset (HO) CDI. Despite including test type in the risk adjustment, some hospital personnel and other stakeholders are concerned that NAAT use is associated with higher SIRs than EIA use. To investigate this issue, we analyzed NHSN data from acute-care hospitals for July 1, 2017, through June 30, 2018. Methods: Calendar quarters where CDI test type was reported as NAAT (includes NAAT, glutamate dehydrogenase (GDH)+NAAT and GDH+EIA followed by NAAT if discrepant) or EIA (includes EIA and GDH+EIA) were selected. HO-CDI SIRs were calculated for facility-wide inpatient locations. We conducted the following 2 analyses: (1) Among hospitals that did not switch their test type, we compared the distribution of HO incident rates and SIRs by those reporting NAAT versus EIA. (2) Among hospitals that switched their test type, we selected quarters with a stable switch pattern of 2 consecutive quarters of each of EIA and NAAT (categorized as EIA-to-NAAT or NAAT-to-EIA). Pooled semiannual SIRs for EIA and NAAT were calculated, and a paired t test was used to evaluate the difference in SIRs by switch pattern. Results: Most hospitals did not switch test types (3,242, 89%), and 2,872 (89%) reported sufficient data to calculate an SIR, with 2,444 (85%) using NAAT. The crude pooled HO CDI incidence rates for hospitals using EIAs clustered at the lower end of the histogram versus rates for NAATs (Fig. 1). The SIR distributions, both NAATs and EIAs, overlapped substantially and covered a similar range of SIR values (Fig. 1). Among hospitals with a switch pattern, hospitals were equally likely to have an increase or decrease in their SIRs (Fig. 2). The mean SIR difference for the 42 hospitals switching from EIA to NAAT was 0.048 (95% CI, −0.189 to 0.284; P = .688). The mean SIR difference for the 26 hospitals switching from NAAT to EIA was 0.162 (95% CI, −0.048 to 0.371; P = .124). Conclusions: The pattern of SIR distribution for both NAAT and EIA substantiate the soundness of the NHSN’s risk adjustment for CDI test types. Switching test type did not produce a consistent directional pattern in SIR that was statistically significant.Funding: NoneDisclosures: None

Importance Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results Patients’ ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Liver transplant recipients are at high risk for surgical site infections (SSIs). Limited data are available on SSI epidemiology following liver transplant procedures (LTPs). We analyzed data on SSIs from 2015 to 2018 reported to CDC's National Healthcare Safety Network to determine rates, pathogen distribution, and antimicrobial resistance after LTPs and other hepatic, biliary, or pancreatic procedures (BILIs). LTP and BILI SSI rates were 5.7% and 5.9%, respectively. The odds of SSI after LTP were lower than after BILI (adjusted odds ratio = 0.70, 95% confidence interval 0.57‐0.85). Among LTP SSIs, 43.1% were caused by Enterococcus spp., 17.2% by Candida spp., and 15.0% by coagulase‐negative Staphylococcus spp. (CNS). Percentages of SSIs caused by Enterococcus faecium or CNS were higher after LTPs than BILIs, whereas percentages of SSIs caused by Enterobacteriaceae, Enterococcus faecalis, or viridans streptococci were higher after BILIs. Antimicrobial resistance was common in LTP SSI pathogens, including E. faecium (69.4% vancomycin resistant); Escherichia coli (68.8% fluoroquinolone non‐susceptible and 44.7% extended spectrum cephalosporin [ESC] non‐susceptible); and Klebsiella pneumoniae and K. oxytoca (39.4% fluoroquinolone non‐susceptible and 54.5% ESC non‐susceptible). National LTP SSI pathogen and resistance data can help prioritize studies to determine effective interventions to prevent SSIs and reduce antimicrobial resistance in liver transplant recipients.

Thirty Clostridioides difficile isolates collected in 2016 through the Centers for Disease Control and Prevention Emerging Infections Program were selected for reference antimicrobial susceptibility testing and whole-genome sequencing. Here, we present the genetic characteristics of these isolates and announce their availability in the CDC & FDA Antibiotic Resistance Isolate Bank.

We assessed viral co-infections in 155 patients with community-associated Clostridioides difficile infection in five U.S. sites during December 2012-February 2013. Eighteen patients (12%) tested positive for norovirus (n = 10), adenovirus (n = 4), rotavirus (n = 3), or sapovirus (n = 1). Co-infected patients were more likely than non-co-infected patients to have nausea or vomiting (56% vs 31%; p = 0.04), suggesting that viral co-pathogens contributed to symptoms in some patients. There were no significant differences in prior healthcare or medication exposures or in CDI complications.

We evaluated the association between socioeconomic status (SES) and community-associated Clostridioides difficile infection (CA-CDI) incidence across 2474 census tracts in 10 states. Highly correlated community-level SES variables were transformed into distinct factors using factor analysis. We found low SES communities were associated with higher CA-CDI incidence.

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)

Background: There is great enthusiasm for the potential of decision support tools embedded in the electronic medical record to improve antimicrobial use in hospitals. Yet they are often limited in their ability to change prescriber behavior. Analyzing these tools using an interactive sociotechnical approach (ISTA) can identify barriers and facilitators to the implementation of electronic decision support (EDS) in antimicrobial stewardship. Objective: To examine prescriber and antimicrobial steward perceptions of EDS using an ISTA approach in the preimplementation phase of an antimicrobial stewardship intervention. Methods: We conducted semistructured interviews with prescribers and stewards from 4 hospitals in 2 health systems in the context of a multicomponent intervention to improve the use of fluoroquinolones and extended-spectrum cephalosporins. Sites planned to implement various EDS elements including order sets, antimicrobial time outs, and audit with feedback stewardship notes in the medical record. Interviews elicited respondent perceptions about the planned intervention. Two analysts systematically coded transcripts using an ISTA framework in NVivo12 software. Results: Interviews with 64 respondents were conducted: 38 physicians, 7 nurses, 6 advanced practice providers, and 13 pharmacists. We identified 4 key sociotechnical interaction types likely to influence stewardship EDS implementation. First, EDS changes the communication patterns and practices of antimicrobial stewards in a way that improves efficiency but decreases vital social interaction with prescribers to facilitate behavior change. Second, there is a gap between what stewards envision for EDS and that which is possible to build in a timely manner by hospital information technology specialists. As a result, there is often a months- to years-long delay from proposal to implementation, which negatively affects intervention acceptance. Third, prescribers expressed great enthusiasm for stewardship EDS that would simplify their workload, allow them to complete important work tasks, and save time. They strongly objected to stewardship EDS that was disruptive without a compelling purpose or did not integrate smoothly with pre-existing technology infrastructure. Fourth, physician prescribers attributed social and emotional meaning to stewardship EDS, suggesting that these tools can undermine professional authority, autonomy, and confidence. Conclusions: Implementing stewardship EDS in a way that improves the use of antimicrobials while minimizing unintended negative consequences requires attention to the interplay between new EDS and an organization’s existing workflow, culture, social interactions and technologies. Implementing EDS in stewardship will require attention to these domains to realize the full potential of these tools and to avoid negative unintended consequences.Funding: NoneDisclosures: None

Background: The epidemic NAP1/027 Clostridioides difficile strain (MLST1, ST1) that emerged in the mid-2000 is on the decline. The current distribution of C. difficile strain types and their transmission dynamics are poorly defined. We performed whole-genome sequencing (WGS) of C. difficile isolates in 2 regions to identify the predominant multilocus sequence types (MLSTs) in community- and healthcare-associated cases and potential transmission between cases using whole-genome single-nucleotide polymorphism (SNP) analysis. Methods: Isolates were collected through the CDC Emerging Infections Program population-based surveillance for C. difficile infections (CDI) for 3 months between 2016 and 2017 in 5 Minnesota counties and 1 New York county. Isolates were limited to incident cases (CDI in a county resident with no positive C. difficile test in the preceding 8 weeks). Cases were classified as healthcare associated (HA-CDI) or community associated (CA-CDI) based on healthcare exposures as previously described. WGS was performed on an Illumina Miseq. The CFSAN (FDA) pipeline was used to compute whole-genome SNPs, SPAdes was used for assembly, and MLST was assigned according to www.pubmlst.org. Results: Of 431 isolates, 269 originated from New York and 162 from Minnesota; 203 cases were classified as CA-CDI and 221 as HA-CDI. The proportion of CA-CDI cases was higher in Minnesota than in New York: 62% vs 38%. The predominant MLSTs across both sites were ST42 (9%), ST8 (8%), and ST2 (8%). MLSTs more frequently encountered in HA-CDI than CA-CDI included ST1 (note that this ST includes PCR Ribotype 027; 76% HA-CDI), ST53 (84% HA-CDI), and ST43 (80% HA-CDI). In contrast, ST110 (63% CA-CDI) and ST3 (67% CA-CDI) were more commonly isolated from CA-CDI cases. ST1 accounted for 7.6% of circulating strains and was more common in New York than Minnesota (10% vs 3%) and was concentrated among New York HA-CDI cases. Also, 412 isolates (1 per patient) were included in the final whole-genome SNP analysis. Of these, only 12 pairs were separated by 0–3 SNPs, indicating potential transmission, and most involved HA-CDI cases. ST1, ST17, and ST46 accounted for 8 of 12 pairs, with ST17 and ST46 potentially forming small clusters. Conclusions: This analysis provides a snapshot of the current genomic epidemiology of C. difficile across 2 geographically and epidemiologically distinct regions of the United States and supports other studies suggesting that the role of direct transmission in the spread of CDI may be limited.Funding: NoneDisclosures: None

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.

Background Few data suggest that Clostridioides difficile infections (CDIs) detected by toxin enzyme immunoassay (EIA) are more severe and have worse outcomes than those detected by nucleic acid amplification tests (NAATs) only. We compared toxin- positive and NAAT-positive-only CDI across geographically diverse sites. Methods A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases were detected during 2014–2015 by a testing algorithm (specimens initially tested by glutamate dehydrogenase and toxin EIA; if discordant results, specimens were reflexed to NAAT) and classified as toxin positive or NAAT positive only. Medical charts were reviewed. Multivariable logistic regression models were used to compare CDI-related complications, recurrence, and 30-day mortality between the 2 groups. Results Of 4878 cases, 2160 (44.3%) were toxin positive and 2718 (55.7%) were NAAT positive only. More toxin-positive than NAAT-positive-only cases were aged ≥65 years (48.2% vs 38.0%; P < .0001), had ≥3 unformed stools for ≥1 day (43.9% vs 36.6%; P < .0001), and had white blood cell counts ≥15 000 cells/µL (31.4% vs 21.4%; P < .0001). In multivariable analysis, toxin positivity was associated with recurrence (adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.61–2.23), but not with CDI-related complications (aOR, 0.91; 95% CI, .67–1.23) or 30-day mortality (aOR, 0.95; 95% CI, .73–1.24). Conclusions Toxin-positive CDI is more severe, but there were no differences in adjusted CDI-related complication and mortality rates between toxin-positive and NAAT-positive-only CDI that were detected by an algorithm that utilized an initial glutamate dehydrogenase screening test.

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 < 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.

OBJECTIVETo determine the source of a healthcare-associated outbreak ofPantoea agglomeransbloodstream infections.DESIGNEpidemiologic investigation of the outbreak.SETTINGOncology clinic (clinic A).METHODSCases were defined asPantoeaisolation from blood or catheter tip cultures of clinic A patients during July 2012–May 2013. Clinic A medical charts and laboratory records were reviewed; infection prevention practices and the facility’s water system were evaluated. Environmental samples were collected for culture. Clinical and environmentalP. agglomeransisolates were compared using pulsed-field gel electrophoresis.RESULTSTwelve cases were identified; median (range) age was 65 (41–78) years. All patients had malignant tumors and had received infusions at clinic A. Deficiencies in parenteral medication preparation and handling were identified (eg, placing infusates near sinks with potential for splash-back contamination). Facility inspection revealed substantial dead-end water piping and inadequate chlorine residual in tap water from multiple sinks, including the pharmacy clean room sink.P. agglomeranswas isolated from composite surface swabs of 7 sinks and an ice machine; the pharmacy clean room sink isolate was indistinguishable by pulsed-field gel electrophoresis from 7 of 9 available patient isolates.CONCLUSIONSExposure of locally prepared infusates to a contaminated pharmacy sink caused the outbreak. Improvements in parenteral medication preparation, including moving chemotherapy preparation offsite, along with terminal sink cleaning and water system remediation ended the outbreak. Greater awareness of recommended medication preparation and handling practices as well as further efforts to better define the contribution of contaminated sinks and plumbing deficiencies to healthcare-associated infections are needed.Infect Control Hosp Epidemiol2017;38:314–319

Background: Chlorhexidine bathing reduces bacterial skin colonization and prevents infections in specific patient populations. As chlorhexidine use becomes more widespread, concerns about bacterial tolerance to chlorhexidine have increased; however, testing for chlorhexidine minimum inhibitory concentrations (MICs) is challenging. We adapted a broth microdilution (BMD) method to determine whether chlorhexidine MICs changed over time among 4 important healthcare-associated pathogens. Methods: Antibiotic-resistant bacterial isolates (Staphylococcus aureus from 2005 to 2019 and Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex from 2011 to 2019) were collected through Emerging Infections Program surveillance in 2 sites (Georgia and Tennessee) or through public health reporting in 1 site (Orange County, California). A convenience sample of isolates were collected from facilities with varying amounts of chlorhexidine use. We performed BMD testing using laboratory-developed panels with chlorhexidine digluconate concentrations ranging from 0.125 to 64 μg/mL. After successfully establishing reproducibility with quality control organisms, 3 laboratories performed MIC testing. For each organism, epidemiological cutoff values (ECVs) were established using ECOFFinder. Results: Among 538 isolates tested (129 S. aureus, 158 E. coli, 142 K. pneumoniae, and 109 E. cloacae complex), S. aureus, E. coli, K. pneumoniae, and E. cloacae complex ECVs were 8, 4, 64, and 64 µg/mL, respectively (Table 1). Moreover, 14 isolates had an MIC above the ECV (12 E. coli and 2 E. cloacae complex). The MIC50 of each species is reported over time (Table 2). Conclusions: Using an adapted BMD method, we found that chlorhexidine MICs did not increase over time among a limited sample of S. aureus, E. coli, K. pneumoniae, and E. cloacae complex isolates. Although these results are reassuring, continued surveillance for elevated chlorhexidine MICs in isolates from patients with well-characterized chlorhexidine exposure is needed as chlorhexidine use increases.Funding: NoneDisclosures: None

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.

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.

Clostridioides difficile (formerly Clostridium difficile) infection is the most frequently identified health care–associated infection in the United States. C difficile has also emerged as a cause of community-associated diarrhea, resulting in increased incidence of community-associated infection. Clinical illness ranges in severity from mild diarrhea to fulminant colitis and death. Appropriate management of infection requires understanding of the various diagnostic assays and therapeutic options as well as relevant measures to infection prevention. This article provides updated recommendations regarding the prevention, diagnosis, and treatment of incident and recurrent C difficile infection.

Background Due to complex invasive medical procedures and compromised immunity, solid-organ transplant (SOT) patients are at high risk for infections. However, whether SOT patients are at higher risk than other hospitalized patients for selected healthcare-associated infections (HAI), such as central line-associated bloodstream infections (CLABSI) or catheter-associated urinary tract infections (CAUTI), or for infections with antimicrobial-resistant (AR) pathogens, is not well described. We analyzed data reported to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN) from inpatient SOT units and compared CLABSI and CAUTI rates and AR in hospitals with both SOT and non-SOT units. Methods We analyzed 2015–2017 CLABSI and CAUTI data reported to NHSN from hospitals with adult or pediatric inpatient SOT units. We calculated CLABSI and CAUTI incidence rates per 1,000 central-line days (CLD) and urinary catheter days (UCD), respectively, and compared rates, pathogen distributions, and AR among events attributed to three unit types: (1) SOT units; (2) adult, pediatric, and neonatal critical care units; and (3) adult and pediatric medical, surgical, and combined medical-surgical wards. We compared proportions using χ 2 tests and determined statistical significance at P ≤ 0.05. Results CLABSI and CAUTI rates in SOT units were lower than rates in critical care units, but higher than rates in wards (table). Although the most common CLABSI and CAUTI pathogens were similar in all three unit types, the prevalence of individual pathogens differed (figure). Among CLABSI pathogens, Enterococcus faecium, Escherichia coli, and Klebsiella pneumoniae or oxytoca were significantly more prevalent in SOT compared with critical care units. Vancomycin resistance among CLABSI E. faecium was significantly lower (71.4% vs. 87.5%) and fluoroquinolone resistance among CAUTI E. coli was significantly higher (49.3% vs. 32.5%) in SOT compared with critical care units. Conclusion SOT units have lower CLABSI and CAUTI rates compared with critical care units. Differences in pathogens and AR among device-associated HAIs in SOT units should be considered when implementing infection prevention and treatment policies. Disclosures All authors: No reported disclosures.

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.

A new, less restrictive definition increases detection of Klebsiella pneumoniae carbapenemase producers., Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non–CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase–producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.

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.

We assessed for vancomycin-resistant Staphylococcus aureus (VRSA) precursor organisms in southeastern Michigan, an area known to have VRSA. The prevalence was 2.5% (pSK41-positive methicillin-resistant S. aureus, 2009–2011) and 1.5% (Inc18-positive vancomycin-resistant Enterococcus, 2006–2013); Inc18 prevalence significantly decreased after 2009 (3.7% to 0.82%). Risk factors for pSK41 included intravenous vancomycin exposure.Infect Control Hosp Epidemiol 2014;35(12):1531–1534

Herbaspirillum species are gram-negative, flagellate members of the Betaproteobacteria class of bacteria, which includes Burkholderia, Ralstonia, and other plant-associated bacteria. Most species of Herbaspirillum are nitrogen-fixing bacteria that are commonly found in the rhizosphere and colonize plants endophytically. They are found in the roots and stems of maize, rice, beans, bananas, sugar cane, pineapple, and other plants [1, 2] and they have been recovered from groundwater [3] and drinking water distribution systems [4] as well. In the published literature, Herbaspirillum species have been recovered from respiratory secretions of patients with cystic fibrosis (CF) [5, 6] and described in case reports of 4 patients with bacteremia, 2 of whom had an underlying malignancy [6–9]. Its close phylogenetic and phenotypic resemblance to Burkholderia cepacia complex led to initial misidentification in 2 of the 4 reported cases [6, 9]. To our knowledge, no outbreaks or clusters of cases have been previously reported in the literature. Between June and August 2011, we identified an initial cluster of 5 patients with bloodstream infection caused by a gram-negative bacillus, initially identified as B. cepacia complex. The isolates were susceptible to all antibiotics tested, whereas over the years, previous B. cepacia isolates recovered in our institution were resistant to at least 1 and up to 4 of the antibiotics tested. These isolates were submitted to the Cystic Fibrosis Foundation Burkholderia cepacia Research Laboratory and Repository at the University of Michigan and were subsequently reidentified as Herbaspirillum species. We conducted a joint investigation with the Texas Department of State Health Services (TDSHS) and the Centers for Disease Control and Prevention (CDC) to determine the nature and extent of the cluster of Herbaspirillum species infections. This report describes the clinical and epidemiologic findings from our investigation and provides a review of the literature.

Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant organisms with few treatment options that cause infections associated with substantial morbidity and mortality. CRE outbreaks have been increasingly reported worldwide and are mainly due to the emergence and spread of strains that produce carbapenemases. In the United States, transmission of CRE is primarily driven by the spread of organisms carrying the Klebsiella pneumoniae carbapenemase enzyme, but other carbapenemase enzymes, such as the New-Delhi metallo-β-lactamase, have also emerged. Currently recommended control strategies for healthcare facilities include the detection of patients infected or colonized with CRE and implementation of measures to prevent further spread. In addition to efforts in individual facilities, effective CRE control requires coordination across all healthcare facilities in a region. This review describes the current epidemiology and surveillance of CRE in the United States and the recommended approach to prevention.

Objective.To determine the source and identify control measures of an outbreak ofTsukamurellaspecies bloodstream infections at an outpatient oncology facility.Design.Epidemiologic investigation of the outbreak with a case-control study.Methods.A case was an infection in whichTsukamurellaspecies was isolated from a blood or catheter tip culture during the period January 2011 through June 2012 from a patient of the oncology clinic. Laboratory records of area hospitals and patient charts were reviewed. A case-control study was conducted among clinic patients to identify risk factors forTsukamurellaspecies bloodstream infection. Clinic staff were interviewed, and infection control practices were assessed.Results.Fifteen cases ofTsukamurella (Tsukamurella pulmonisorTsukamurella tyrosinosolvens) bloodstream infection were identified, all in patients with underlying malignancy and indwelling central lines. The median age of case patients was 68 years; 47% were male. The only significant risk factor for infection was receipt of saline flush from the clinic during the period September–October 2011 (P= .03), when the clinic had been preparing saline flush from a common-source bag of saline. Other infection control deficiencies that were identified at the clinic included suboptimal procedures for central line access and preparation of chemotherapy.Conclusion.Although multiple infection control lapses were identified, the outbreak was likely caused by improper preparation of saline flush syringes by the clinic. The outbreak demonstrates that bloodstream infections among oncology patients can result from improper infection control practices and highlights the critical need for increased attention to and oversight of infection control in outpatient oncology settings.

We investigated a multifacility outbreak of acute hepatitis B virus infection involving 21 residents across 10 assisted living facilities in Texas during the period January 2008 through July 2010. Epidemiologic and laboratory data suggested that these infections belonged to a single outbreak. The only common exposure was receipt of assisted monitoring of blood glucose from the same home health care agency. Improved infection control oversight and training of assisted living facility and home health care agency personnel providing assisted monitoring of blood glucose is needed.

Background US laboratories are increasingly using nucleic acid amplification tests (NAAT) to diagnose Clostridium difficile infection (CDI) due to their increased sensitivity over toxin enzyme immunoassays (EIA), but NAATs may be more likely than toxin EIAs to detect colonization rather than true disease. Limited data indicate patients positive by toxin EIA (toxin+) have worse outcomes than those positive by NAAT (NAAT+) only, suggesting toxin EIA detects true infection more often than NAAT. We used multisite CDI surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program to compare clinical course and outcomes between toxin+ and NAAT+ only patients. Methods A case was defined as a positive C. difficile test in a person ≥1 year old with no positive tests in the prior 8 weeks. Cases detected during 2014–2015 by a testing algorithm using toxin EIA and NAAT were classified as toxin+ or NAAT+ only. Medical charts were reviewed. Death data were obtained from state death registries. Multivariable logistic regression models were used to compare CDI recurrence and 90-day mortality between the two groups, adjusting for age, sex, race, Charlson comorbidity index, and receipt of oral vancomycin. For the outcome of recurrence, we also adjusted for history of CDI in the prior 6 months. Results Of 4,878 cases, 2160 (44%) were toxin+ and 2,718 (56%) were NAAT+ only. Toxin+ cases were more likely than NAAT+ only cases to be ≥65 years old (48% vs. 38%; P < 0.0001), have white blood cells ≥15,000/µL (483/1,539 [31%] vs. 423/1,978 [21%]; P < 0.0001), and have received oral vancomycin ≤3 days of diagnosis (32% vs. 29%; P = 0.03). Comparing toxin+ to NAAT+ only cases, 21% vs. 11% had a recurrence (P < 0.0001), of which 71% vs. 33% had a toxin+ recurrence (P < 0.0001), and 10% vs. 9% died ≤90 days of diagnosis (P = 0.12). In multivariable analysis, a toxin+ result was associated with recurrence (adjusted odds ratio [aOR]: 1.89, 95% CI: 1.61–2.22) but not with 90-day mortality (aOR: 0.99; 95% CI: 0.81–1.22). Conclusion Toxin+ CDI is more severe by some markers and more likely to recur as toxin+. However, there was no difference in adjusted mortality, which may reflect an effect on mortality in NAAT+ only cases from mild CDI, receipt of unnecessary CDI treatment, or other factors. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Background In 2009, the Centers for Disease Control and Prevention (CDC) implemented Clostridioides difficile infection (CDI) surveillance through the Emerging Infections Program (EIP) to monitor the incidence and evolving epidemiology of CDI in the United States. Since 2012, ribotypes (RTs) 027, 106, 002, 014, and 020 have constituted the top five strain types among both US community- and healthcare-associated isolates. Here we describe the changes in molecular epidemiology of C. difficile isolates collected in the United States in 2017. Methods In 2017, CDI surveillance was conducted at 10 EIP sites (CA, CO, CT, GA, MD, MN, NM, NY, OR, and TN). A convenience sample of clinical laboratories across EIP sites submitted C. difficile-positive stool specimens to the MN Department of Health Public Health Laboratory and Hines VA Hospital (IL) for culture. Isolates were forwarded to CDC and characterized by capillary-based PCR-ribotyping and PCR detection of tcdA, tcdB, cdtA, cdtB, and deletions in tcdC. Results In 2017, 1,051 C. difficile isolates were submitted; the total number of isolates received from each site ranged from 11 to 286 with a median of 85.5. In total, 143 RTs were observed, with the majority of isolates harboring toxin genes tcdA and tcdB (95%) and a wild-type tcdC sequence (71%). Among 556 healthcare-associated isolates, RT 027 was the most prevalent and the top RT at 5 sites (CA, GA, MD, NM, TN). Ribotype 106 was the most prevalent among 495 community-associated CA isolates and the top RT at 6 sites (CO, CT, GA, MD, MN, TN). Ribotype 027 significantly decreased from 2012 to 2017 among both healthcare-associated (21% vs 15%; p = 0.02) and community-associated isolates (17% vs 6%; P < 0.0001). Among healthcare-associated isolates, RT 076, which was observed in 8 EIP sites, increased from 2% in 2016 to 5% in 2017 (p = 0.05) and replaced RT 020 as one of the top 5 healthcare-associated RTs in 2017. Conclusion Despite an overall decline since 2012, RT 027 remained the most prevalent RT among healthcare-associated isolates submitted in 2017. The increased frequency of RT 076 among healthcare-associated isolates submitted in 2017 highlights the evolving molecular epidemiology of C. difficile and the need for continued surveillance to monitor potential emerging strains. Disclosures All authors: No reported disclosures.

In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1). The charges to the Working Group were to (1) critically review a draft, streamlined VAP surveillance definition developed for use in adult patients; (2) suggest modifications to enhance the reliability and credibility of the surveillance definition within the critical care and infection prevention communities; and (3) propose a final adult surveillance definition algorithm to be implemented in the CDC's National Healthcare Safety Network (NHSN), taking into consideration the potential future use of the definition algorithm in public reporting, interfacility comparisons, and pay-for-reporting and pay-for-performance programs.

Objective:To develop and implement an objective, reliable approach to surveillance for ventilator-associated events in adult patients.Design:The Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group in September 2011.

Background.Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Incl8-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer.Objective.Identify the prevalence of VRSA precursor organisms.Design.Prospective cohort with embedded case-control study.Participants.Southeastern Michigan adults with chronic lower-extremity wounds.Methods.Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Incl8-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis).Results.Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Incl8-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses.Conclusions.Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.

During a pneumococcal disease outbreak in a pediatric psychiatric unit in a hospital in Rhode Island, USA, 6 (30%) of 20 patients and staff were colonized with Streptococcus pneumoniae serotype 15A, which is not included in pneumococcal vaccines. The outbreak subsided after implementation of antimicrobial drug prophylaxis and enhanced infection control measures.

Background Incidence of Clostridium difficile infection (CDI) in children has been shown to be highest among those aged 1 to 3 years, with similar clinical presentation, disease severity, and outcomes as older children. In addition, a large proportion of CDI in children are community-associated (CA), but few data exist regarding associated risk factors. We sought to identify CA-CDI risk factors in younger children. Methods We enrolled children from 8 geographically-diverse U.S. sites during October 2014–February 2016. Case-patients were defined as children aged 12–60 months with a positive C. difficile stool specimen collected as an outpatient or within 3 days of hospitalization, who had no healthcare facility admission in the prior 12 weeks and no history of CDI. Each case-patient was matched to one randomly selected control (child with no prior history of CDI) by site and age group. Caretakers were interviewed about participants’ relevant exposures in the 12 weeks prior to case-patient’s illness onset date; univariate analysis was performed using exact conditional logistic regression. Results Of 138 children, 43.5% were female; 69.6% were 12–23 months old. A significantly higher proportion of cases than controls had: an underlying chronic medical condition (33.3% vs 11.9%; P = 0.02); a neonatal intensive care unit (NICU) stay at time of birth (26.9% vs 13.2%; P = 0.04); or recent antibiotic exposure (53.6% vs 20.6%; P = 0.0001). More cases than controls had recent higher-risk outpatient healthcare exposures (emergency department, outpatient procedure and surgical centers, hospital-based outpatient settings, or urgent care) (34.9% vs 19.1%; P = 0.06) or a household member with diarrhea (36.2% vs 20.6%; P = 0.05). No difference was found in the proportion of cases and controls who had a feeding tube (2.9% vs 0%; P = 0.50) or a recent exposure to gastric acid suppressants (6.1% vs 2.9%; P = 0.63). Conclusion Young children with underlying disease, NICU stay, or recent antibiotic use might be at higher risk for CA-CDI. Improving outpatient antibiotic use, particularly among children with comorbidities, might reduce CA-CDI in this population. Further investigation of other risk factors, including outpatient healthcare and household exposures, is needed. Disclosures All authors: No reported disclosures.

Background. In Connecticut, despite hazards of raw milk consumption, attempts to ban raw milk sales have been unsuccessful. In July 2008, 2 children experienced Escherichia coli O157-associated hemolytic uremic syndrome (HUS) after consuming raw milk purchased at a retail market and a farm (farm X). We investigated to determine the outbreak source and control measures. Methods. Confirmed cases were HUS diagnosis or E. coli O157:NM infections with isolates matching outbreak strains among patients during June to July 2008. Probable cases were diarrheal illness among farm X customers during the same period. We conducted case-control studies to determine the source of E. coli 0157 exposure and assess for dose-response relation between illness and frequency of raw milk consumption. Farm X dairy practices were evaluated; stool specimens of humans and animals were cultured for E. coli O157. Staff time and laboratory and medical costs were calculated. Results. We identified 14 cases (7 confirmed). Five (36%) case patients required hospitalization; 3 (21%) experienced HUS. No deaths were reported. Raw milk consumption was associated with illness (P = .008); a dose-response relation was demonstrated (P = .01). Dairy practices reflected industry standards. E. coli O157:NM outbreak strains were isolated from stool specimens of 6 case patients and 1 milking cow. The total estimated outbreak cost was $413,402. Conclusions. Farm X's raw milk was the outbreak source despite no violations of current raw milk regulatory standards. This outbreak resulted in substantial costs and proposed legislation to prohibit nonfarm retail sale, strengthen advisory labels, and increase raw milk testing for pathogens.

We investigated the first documented university outbreak of the 2009 pandemic influenza A(H1N1) to identify factors associated with disease transmission. An online student survey was administered to assess risk factors for influenza-like illness (ILI), defined as fever with cough or sore throat. Of 6049 survey respondents, 567 (9%) experienced ILI during 27 March to 9 May 2009. Studying with an ill contact (adjusted risk ratios [aRR], 1.29; 95% confidence intervals [CI], 1.01-1.65) and caring for an ill contact (aRR, 1.51; CI, 1.14-2.01) any time during 27 March to 9 May were predictors for ILI. Respondents reported that 680 (6%) of 11,411 housemates were ill; living with an ill housemate was a predictor for ILI (RR, 1.38; CI, 1.04-1.83). Close contact or prolonged exposures to ill persons were likely associated with experiencing ILI. Self-protective measures should be promoted in university populations to mitigate transmission.

Background Traditionally a healthcare-associated infection, Clostridium difficile infection (CDI) is increasingly emerging in communities. Health disparities in CDI exist, but the social determinants of health that influence community-associated (CA) CDI are unknown. We used factor analysis and disparate data sources to identify area-based socioeconomic status (SES) factors associated with CA-CDI incidence. Methods CDC’s Emerging Infections Program conducts population-based CDI surveillance in 35 US counties. A CA-CDI case is defined as a positive C. difficile specimen collected as an outpatient or within 3 days of hospitalization in a person aged ≥1 year without a positive test in the prior 8 weeks or an overnight stay in a healthcare facility in the prior 12 weeks. 2014–2015 CA-CDI case addresses were geocoded to a 2010 census tract (CT) and incidence rates were calculated. CT-level SES variables were obtained from the 2011–2015 American Community Survey. The Health Resources and Services Administration provided medically underserved area (MUA) designations. Exploratory factor analysis transformed 15 highly correlated SES variables into threefactors using scree plot and Kaiser criteria: “Low Income,” “Foreign-born,” and “High Income.” To account for CT-level clustering, a negative binomial generalized linear mixed model was used to evaluate the associations of these factors and MUA with CA-CDI incidence, adjusting for age, sex, race and diagnostic test. Results Of 13,903 CA-CDI geocoded cases, 63% were female, 80% were white, and 36% were aged ≥65 years. Annual CA-CDI incidence was 63.4/100,000 persons. In multivariable analysis, “Low Income” (rate ratio [RR]: 1.09; 95% confidence interval [CI]: 1.05–1.13) and “High Income” (RR: 0.90; CI: 0.87–0.93) were significantly associated with CA-CDI incidence. Conclusion Factor analysis was instrumental in identifying key drivers of disparities among interrelated SES variables. Low-income areas were surprisingly associated with higher CA-CDI incidence, given that known CDI risk factors include increased access to healthcare. Understanding how SES factors might impact CA-CDI incidence can inform prevention strategies in low-income areas. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.