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Carbapenem-resistant Enterobacterales (CRE) are a growing public health concern due to resistance to multiple antibiotics and potential to cause health care-associated infections with high mortality. Carbapenemase-producing CRE are of particular concern given that carbapenemase-encoding genes often are located on mobile genetic elements that may spread between different organisms and species. In this study, we performed phenotypic and genotypic characterization of CRE collected at eight U.S. sites participating in active population- and laboratory-based surveillance of carbapenem-resistant organisms. Among 421 CRE tested, the majority were isolated from urine (

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case–control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

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 The COVID-19 pandemic changed accessibility of care and practices within healthcare environments. This period has been associated with healthcare-associated infection outbreaks and shifts in healthcare-associated infectious disease epidemiology. This study’s objective is to describe changes in rates and characteristics of antimicrobial-resistant gram negative and Clostridioides difficile (CD) infections during the COVID-19 pandemic in Bernalillo County, New Mexico. Methods The NM EIP, a collaboration between University of New Mexico and the NM DOH, conducts ongoing laboratory- and population-based surveillance of infectious disease including Clostridium difficile, extended-spectrum beta lactamase (ESBL-E) and carbapenemase-producing gram negative bacteria (CRE). Stata statistical software was used for retrospective analysis of rates and characteristics on NM EIP data from Bernalillo county, NM between 2016 and 2021. Results Reported C. difficile rates decreased from 76 to 49 cases/month and ESBL-producing Enterobacterales decreased from 145 to 86 cases/month during the pandemic period from March-December 2020 compared with the prior 14 months. Monthly case counts for 2020 are lowest during initial public health orders for the state of New Mexico. Rates of CRE remained constant between 2018-2021. The proportion of CDI cases originating from long-term care facilities decreased significantly from 17.2% to 10.4% (p=0.006) while the proportion attributable to hospital inpatient and community populations remained constant. The proportion of ESBL-E cases from sterile sample sites increased from 3.1% to 4.9% (p=0.05) and the proportion of patients who died within 30 days or prior to discharge increased from 2.2% to 3.2% (p=0.019). Conclusion Rates and characteristics of CD and ESBL-E infections in Bernalillo county NM changed significantly during the COVID-19 pandemic, while rates of CRE remained constant. It is still unclear whether this is related to changes in actual disease rates due to risk factor exposure (healthcare), or if this trend reflects changes in care-seeking behavior and/or reporting of cases. Disclosures All Authors: No reported disclosures.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

We evaluated healthcare facility use of International Classification of Diseases, Tenth Revision (ICD-10) codes for culture-confirmed candidemia cases detected by active public health surveillance during 2019–2020. Most cases (56%) did not receive a candidiasis code, suggesting that studies relying on ICD-10 codes likely underestimate disease burden.

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

Background The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. Methods We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention’s Emerging Infections Program during April–August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher’s exact tests. Results Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit–level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). Conclusions One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

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...

ObjectiveThe incidence of infections from extended-spectrum β-lactamase (ESBL)–producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites.MethodsDuring October–December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia coli or Klebsiella pneumoniae/oxytoca resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates.ResultsWe identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli. Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a blaCTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated.ConclusionsThe burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.

Carbapenem-resistant Enterobacterales (CRE) are usually healthcare-associated but are also emerging in the community.Active, population-based surveillance was conducted to identify case-patients with cultures positive for Enterobacterales not susceptible to a carbapenem (excluding ertapenem) and resistant to all third-generation cephalosporins tested at 8 US sites from January 2012 to December 2015. Medical records were used to classify cases as health care-associated, or as community-associated (CA) if a patient had no known health care risk factors and a culture was collected3 days after hospital admission. Enterobacterales isolates from selected cases were submitted to CDC for whole genome sequencing.We identified 1499 CRE cases in 1194 case-patients; 149 cases (10%) in 139 case-patients were CA. The incidence of CRE cases per 100,000 population was 2.96 (95% CI: 2.81, 3.11) overall and 0.29 (95% CI: 0.25, 0.35) for CA-CRE. Most CA-CRE cases were in White persons (73%), females (84%) and identified from urine cultures (98%). Among the 12 sequenced CA-CRE isolates, 5 (42%) harbored a carbapenemase gene.Ten percent of CRE cases were CA; some isolates from CA-CRE cases harbored carbapenemase genes. Continued CRE surveillance in the community is critical to monitor emergence outside of traditional health care settings.

Background The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. Methods We conducted a test-negative case–control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19–like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). Results The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer–BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (

Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding: NoneDisclosures: None

Background Injection drug use (IDU) is a known, but infrequent risk factor on candidemia; however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia. Methods Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture. Results During 2017, 1191 candidemia cases were identified in patients aged >12 years (incidence: 6.9 per 100 000 population); 128 (10.7%) had IDU history, and this proportion was especially high (34.6%) in patients with candidemia aged 19–44. Patients with candidemia and IDU history were younger than those without (median age, 35 vs 63 years; P < .001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%; relative risk [RR], 0.2 [95% confidence interval {CI}, .1–.5]), abdominal surgery (3.9% vs 17.5%; RR, 0.2 [95% CI, .09–.5]), and total parenteral nutrition (3.9% vs 22.5%; RR, 0.2 [95% CI, .07–.4]). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%; RR, 3.7 [95% CI, 3.1–4.4]), those with hepatitis C (54.7% vs 6.4%; RR, 8.5 [95% CI, 6.5–11.3]), and in people who were homeless (13.3% vs 0.8%; RR, 15.7 [95% CI, 7.1–34.5]). Conclusions Clinicians should consider injection drug use as a risk factor in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19–44 years of age and have community-associated candidemia.

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July-October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY. An incident case was the first P. aeruginosa isolate resistant to antipseudomonal carbapenems from a patient in a 30-day period from any source except the nares, rectum or perirectal area, or feces. We found 294 incident cases among 274 patients. Cases were most commonly identified from respiratory sites (120/294; 40.8%) and urine (111/294; 37.8%); most (223/280; 79.6%) occurred in patients with healthcare facility inpatient stays in the prior year. Genes encoding carbapenemases were identified in 3 (2.3%) of 129 isolates tested. The burden of CRPA was high at facilities under surveillance, but carbapenemase-producing CRPA were rare.

Recent state and federal legislative actions and current recommendations from the World Health Organization seem to suggest that, when it comes to antimicrobial stewardship, use of antimicrobials for prevention, control, or treatment of disease can be ranked in order of appropriateness, which in turn has led, in some instances, to attempts to limit or specifically oppose the routine use of medically important antimicrobials for prevention of disease. In contrast, the AVMA Committee on Antimicrobials believes that attempts to evaluate the degree of antimicrobial stewardship on the basis of therapeutic intent are misguided and that use of antimicrobials for prevention, control, or treatment of disease may comply with the principles of antimicrobial stewardship. It is important that veterinarians and animal caretakers are clear about the reason they may be administering antimicrobials to animals in their care. Concise definitions of prevention, control, and treatment of individuals and populations are necessary to avoid confusion and to help veterinarians clearly communicate their intentions when prescribing or recommending antimicrobial use.

Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection.

Background Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. Methods During 2017–2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. Results Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29–3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. Conclusions A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

Heteroresistance is an underappreciated phenomenon that may be the cause of some unexplained antibiotic treatment failures. Misclassification of heteroresistant isolates as susceptible may lead to inappropriate therapy., Heteroresistance is a form of antibiotic resistance where a bacterial strain is comprised of a minor resistant subpopulation and a majority susceptible subpopulation. We showed previously that colistin heteroresistance can mediate the failure of colistin therapy in an in vivo infection model, even for isolates designated susceptible by clinical diagnostics. We sought to characterize the extent of colistin heteroresistance among the highly drug-resistant carbapenem-resistant Enterobacterales (CRE). We screened 408 isolates for colistin heteroresistance. These isolates were collected between 2012 and 2015 in eight U.S. states as part of active surveillance for CRE. Colistin heteroresistance was detected in 10.1% (41/408) of isolates, and it was more common than conventional homogenous resistance (7.1%, 29/408). Most (93.2%, 38/41) of these heteroresistant isolates were classified as colistin susceptible by standard clinical diagnostic testing. The frequency of colistin heteroresistance was greatest in 2015, the last year of the study. This was especially true among Enterobacter isolates, of which specific species had the highest rates of heteroresistance. Among Klebsiella pneumoniae isolates, which were the majority of isolates tested, there was a closely related cluster of colistin-heteroresistant ST-258 isolates found mostly in Georgia. However, cladistic analysis revealed that, overall, there was significant diversity in the genetic backgrounds of heteroresistant K. pneumoniae isolates. These findings suggest that due to being largely undetected in the clinic, colistin heteroresistance among CRE is underappreciated in the United States.

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: 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.)

BackgroundCandidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US).MethodsIn 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data.ResultsWe identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210–25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318–5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465–8791) deaths occurred during the hospitalization with candidemia.ConclusionsOur analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.

In healthcare settings, Acinetobacter spp. bacteria commonly demonstrate antimicrobial resistance, making them a major treatment challenge. Nearly half of Acinetobacter organisms from clinical cultures in the United States are nonsusceptible to carbapenem antimicrobial drugs. During 2012-2015, we conducted laboratory- and population-based surveillance in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee to determine the incidence of carbapenem-nonsusceptible A. baumannii cultured from urine or normally sterile sites and to describe the demographic and clinical characteristics of patients and cases. We identified 621 cases in 537 patients; crude annual incidence was 1.2 cases/100,000 persons. Among 598 cases for which complete data were available, 528 (88.3%) occurred among patients with exposure to a healthcare facility during the preceding year; 506 (84.6%) patients had an indwelling device. Although incidence was lower than for other healthcare-associated pathogens, cases were associated with substantial illness and death.

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: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core genome MLST (cgMLST) scheme was used to determine phylogeny. Antimicrobial resistance genes were identified using publicly available databases, and chromosomal mechanisms of carbapenem resistance were determined using previously validated genetic markers. Results: There were 189 sequence types (STs) among the 707 sequenced genomes (Fig. 1). The most frequently occurring were high-risk clones ST235 (8.5%) and ST298 (4.7%), which were found across all EIP sites. Carbapenemase genes were identified in 5 (ampC. More than 1 such chromosomal resistance mutation type was present in 37.8% of the isolates. Conclusions: The diversity of the sequence types demonstrates that HAIs caused by CRPA can arise from a variety of strains and that high-risk clones are broadly disseminated across the EIP sites but are a minority of CRPA strains overall. Carbapenem resistance in P. aeruginosa was predominantly driven by chromosomal mutations rather than acquired mechanisms (ie, carbapenemases). The diversity of the CRPA isolates and the lack of carbapenemase genes suggest that this ubiquitous pathogen can readily evolve chromosomal resistance mechanisms, but unlike carbapenemases, these cannot be easily spread through horizontal transfer.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.

Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

Background: Candidemia is associated with high morbidity and mortality. Although risk factors for candidemia and other bloodstream infections (BSIs) overlap, little is known about patient characteristics and the outcomes of polymicrobial infections. We used data from the CDC Emerging Infections Program (EIP) candidemia surveillance to describe polymicrobial candidemia infections and to assess clinical differences compared with Candida-only BSIs. Methods: During January 2017–December 2017 active, population-based candidemia surveillance was conducted in 45 counties in 9 states covering ~6% of the US population through the CDC EIP. A case was defined as a blood culture with Candida spp in a surveillance-area resident; a blood culture >30 days from the initial culture was considered a second case. Demographic and clinical characteristics were abstracted from medical records by trained EIP staff. We examined characteristics of polymicrobial cases, in which Candida and ≥1 non-Candida organism were isolated from a blood specimen on the same day, and compared these to Candida-only cases using logistic regression or t tests using SAS v 9.4 software. Results: Of the 1,221 candidemia cases identified during 2017, 215 (10.2%) were polymicrobial. Among polymicrobial cases, 50 (23%) involved ≥3 organisms. The most common non-Candida organisms were Staphylococcus epidermidis (n = 30, 14%), Enterococcus faecalis (n = 26, 12%), Enterococcus faecium (n = 17, 8%), and Staphylococcus aureus, Klebsiella pneumoniae, and Stenotrophomonas maltophilia (n = 15 each, 7%). Patients with polymicrobial cases were significantly younger than those with Candida-only cases (54.3 vs 60.7 years; P < .0004). Healthcare exposures commonly associated with candidemia like total parenteral nutrition (relative risk [RR], 0.82; 95% CI, 0.60–1.13) and surgery (RR, 0.99; 95% CI, 0.77–1.29) were similar between the 2 groups. Polymicrobial cases had shorter median time from admission to positive culture (1 vs 4 days, P < .001), were more commonly associated with injection drug use (RR, 1.95; 95% CI, 1.46–2.61), and were more likely to be community onset-healthcare associated (RR, 1.91; 95% CI, 1.50–2.44). Polymicrobial cases were associated with shorter hospitalization (14 vs 17 days; P = .031), less ICU care (RR, 0.7; 95% CI, 0.51–0.83), and lower mortality (RR, 0.7; 95% CI, 0.50–0.92). Conclusions: One in 10 candidemia cases were polymicrobial, with nearly one-quarter of those involving ≥3 organisms. Lower mortality among polymicrobial cases is surprising but may reflect the younger age and lower severity of infection of this population. Greater injection drug use, central venous catheter use, and long-term care exposures among polymicrobial cases suggest that injection or catheter practices play a role in these infections and may guide prevention opportunities.Funding: NoneDisclosures: None

Background Candidemia is a bloodstream infection commonly associated with high morbidity and mortality. Failure to clear candidemia can lengthen hospitalization and treatment. Factors associated with candidemia clearance are unknown. Methods We analyzed 2017 candidemia surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program. Data from eight sites (counties in California, Colorado, Georgia, Minnesota, New Mexico, New York, Oregon, and Tennessee) were included. Clearance was defined as having a blood culture negative for Candida ≤30 days after initial culture date (ICD). Cases with unknown clearance, unknown survival outcome, or death ≤30 days of ICD were excluded. Demographic and clinical factors associated with clearance were assessed with bivariate analysis using chi-square tests and multivariable logistic regression to calculate adjusted odds ratios (aOR) using backward selection (p-value< 0.10). Results Of 1,024 candidemia cases, 737 were included and 582 (79%) demonstrated clearance, of which 79% had evidence of clearance ≤5 days after ICD. In bivariate analysis, clearance was associated with central venous catheter (CVC) ≤2 days before ICD, CVC removal ≤7 days after ICD, and systemic antifungal medication within 14 days before ICD. Clearance was inversely associated with black race and admission from another hospital. In multivariable analysis, only race and admission from another hospital were significant predictors; age, sex, and CVC presence and subsequent removal were also retained for their clinical relevance. In the final model, clearance was less likely among black patients (aOR 0.51, 95% confidence interval [CI] 0.29-0.91) and those admitted from another hospital (aOR 0.28, 95% CI 0.11-0.75). Table 1. Bivariate associations for select variables between individuals with documented candidemia clearance and those without documented clearance in eight Emerging Infections Program surveillance sites, 2017 Conclusion We found failure to clear candidemia infection to be associated with black race and prior hospital exposure, but not other factors previously shown to be associated (e.g., comorbidities, CVC presence). These associations could reflect illness severity, access to care, or other obstacles to effective treatment. Additional research is needed to investigate these associations further and identify other factors (e.g., treatment type and timing) to improve outcomes. Disclosures All Authors: No reported disclosures

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 Community-associated Clostridioides difficile infections (CA-CDIs) share many risk factors with health care–associated cases, although the role of socioeconomic factors is poorly understood. This study estimates the influence of several census tract–level measures of socioeconomic status on CA-CDI incidence rates. Methods CA-CDI case data from the New Mexico Emerging Infections Program were analyzed using quasi-Poisson regression modeling. Geocoded cases were assigned census tract–level socioeconomic measures to explore racial, ethnic and socioeconomic disparities in CA-CDI incidence. Results Regression modeling identified census tract–level socioeconomic measures as well as individual and medical measures that together accounted for 57% of the variance in CA-CDI rates. At the census tract level, socioeconomic factors associated with an increase in CA-CDI incidence included a high percentage of individuals lacking health insurance and a low percentage of individuals with low educational attainment. A subanalysis that included racial and ethnic designation revealed that ethnicity had no significant effect, but compared to white race, other races were significantly more likely to acquire CA-CDI. Conclusions Although this work reveals the role of certain socioeconomic and race and ethnicity risk factors in the incidence of CA-CDI, it also underscores the complex relationships that exist between socioeconomic status and access to health care.

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.

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

Background Carbapenem-resistant Enterobacteriacae (CRE) are an urgent US public health threat. CDC reported CRE incidence to be 2.93/100,000 population in 2012–2013 in selected sites but changed the CRE surveillance case definition in 2016 to improve sensitivity for detecting carbapenemase-producing (CP) CRE. We describe CRE epidemiology before and after the change. Methods Eight CDC Emerging Infections Program sites (CO, GA, MD, MN, NM, NY, OR, TN) conducted active, population-based CRE surveillance in selected counties. A case was defined as having an isolate of E. coli, Enterobacter, or Klebsiella meeting a susceptibility phenotype (figure) at a clinical laboratory from urine or a normally sterile body site in a surveillance area resident in a 30-day period. We collected data from medical records and defined cases as community-associated (CA) if no healthcare risk factors were documented. A convenience sample of isolates were tested for carbapenemase genes at CDC by real-time PCR. We calculated incidence rates (per 100,000 population) by using US Census data. Case epidemiology and the proportion of CP-CRE isolates in 2015 versus 2016 were compared. Results In total, 442 incident CRE cases were reported in 2015, and 1,149 cases were reported in 2016. Most isolates were cultured from urine: 87% in 2015 and 92% in 2016 (P < .001). The crude overall pooled mean incidence in 2015 was 2.9 (range by site: 0.45–7.19) and in 2016 was 7.48 (range: 3.13–15.95). The most common CRE genus was Klebsiella (51%) in 2015, and in 2016 was Enterobacter (41%, P < 0.001). Of the subset of CRE isolates tested at CDC, 109/227 (48%) were CP-CRE in 2015 and 109/551 (20%) were CP-CRE in 2016. In 2015, 52/442 (12%) of cases were CA CRE, and in 2016, 267/1,149 (23%) were CA CRE (P < 0.001). In 2016, 3/111 (2.7%) of CA CRE isolates tested were CP-CRE. Conclusion A large increase in reported CRE incidence was observed after the change in the case definition. The new case definition includes a substantially larger number of Enterobacter cases. A decrease in CP-CRE prevalence appears to be driven by an increase in non-CP-CRE cases. Although CP-CRE in the community still appear to be rare, a substantial proportion of phenotypic CRE appear to be CA, and CDC is undertaking efforts to further investigate CA CRE, including CP-CRE. Disclosures G. Dumyati, Seres: Scientific Advisor, Consulting fee.

Background Known risk factors for candidemia include diabetes, malignancy, antibiotics, total parenteral nutrition (TPN), prolonged hospitalization, abdominal surgery, and central venous catheters. Injection drug use (IDU) is not a common risk factor. We used data from CDC Emerging Infections Program’s candidemia surveillance to assess prevalence of IDU among candidemia cases and compare IDU and non-IDU cases. Methods Active, population-based candidemia surveillance was conducted in 45 counties in 9 states during January–December 2017. Data from 2014 to 2016 were available from 4 states and were used to look for trends. A case was defined as blood culture with Candida in a surveillance area resident. We collected clinical information, including IDU in the past 12 months. Differences between IDU and non-IDU cases were tested using logistic regression. Results Of 1,018 candidemia cases in 2017, 123 (12%) occurred in the context of recent IDU (1% in Minnesota and 27% in New Mexico) (Figure 1). In the 4 states with pre-2017 data, the proportion of IDU cases increased from 7% in 2014 to 15% in 2017, with the proportion in Tennessee nearly tripling from 7% to 18% (Figure 2). IDU cases were younger than non-IDU cases (median 34 vs. 62 years, P < 0.001). Compared with non-IDU cases, IDU cases were less likely to have diabetes (16% vs. 35%; OR 0.4, CI 0.2–0.6), malignancies (7% vs. 30%; OR 0.2, CI 0.1–0.3), abdominal surgery (6% vs. 19%; OR 0.3, CI 0.1–0.6), receive TPN (6% vs. 27%; OR 0.2, CI 0.1–0.4) and were more likely to have hepatitis C (96% vs. 47%; OR 16.1, CI 10.4–24.9), be homeless (13% vs. 1%; OR 17.8, CI 7.1–44.6), and have polymicrobial blood cultures (33% vs. 17%; OR 2.4, CI 1.6–3.6). Median time from admission to candidemia was 0.5 vs. 3 days and in-hospital mortality was 7% vs. 28% for IDU and non-IDU cases, respectively. Conclusion In 2017, 1 in 8 candidemia cases had a history of IDU, including a quarter of cases in some sites. The proportion of such cases increased since 2014. IDU cases lacked many of the typical risk factors for candidemia, suggesting that IDU may be an independent risk factor. Given the growing opioid epidemic, further study is necessary to elucidate how people who inject drugs acquire candidemia and design effective interventions for prevention. Disclosures All authors: No reported disclosures.

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 Pseudomonas aeruginosa is intrinsically resistant to many commonly used antimicrobials and carbapenems are often required to treat infections. We describe the epidemiology and crude incidence of carbapenem-resistant P. aeruginosa(CRPA) in the EIP catchment area. Methods From August 1, 2016 through July 31, 2017, we conducted laboratory- and population-based surveillance for CRPA in selected metropolitan areas in Colorado, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. We defined an incident case as the first isolate of P. aeruginosa-resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period. Patient charts were reviewed. A random sample of isolates was screened at CDC for carbapenemases using the modified carbapenem inactivation method (mCIM) and real-time PCR. Results During the 12-month period, we identified 3,042 incident cases among 2,154 patients. The crude incidence rate was 21.2 (95% CI, 20.4–21.9) per 100,000 persons and varied by site (range: 7.7 in Oregon to 31.1 in Maryland). The median age of patients was 64 years (range: Conclusion The burden of CRPA varied by EIP site. Most cases occurred in persons with healthcare exposures and underlying conditions. The majority of isolates were susceptible to at least one first-line antimicrobial. Carbapenemase producers were rare; a more specific phenotypic definition would greatly facilitate surveillance for these isolates. Disclosures All authors: No reported disclosures.

Background Extended-spectrum β-lactamase – producing (ESBL) Enterobacteriaceae pose a serious antibiotic resistance threat, yet gaps remain in our understanding of their epidemiology. New Mexico was one of five Emerging Infection Program (EIP) sites to participate in a surveillance pilot from October 1 to December 31, 2017. Methods A case was defined as a resident of Bernalillo County, NM with E. coli, Klebsiella pneumoniae, or Klebsiella oxytoca cultured from urine or normally sterile body sites resistant to at least one extended-spectrum cephalosporin and nonresistant to all carbapenem antibiotics tested. EIP staff assessed prior healthcare exposures, risk factors, and outcomes through medical record review. Results NM EIP identified 309 incident cases among 288 individuals; 263 medical records were reviewed. Cases ranged in age from 3–95 years, with a median age of 63 years. Most isolates were E. coli (n = 270, 87.4%); 35 (11.3%) were K. pneumoniae and 4 (1.3%) were K. oxytoca. The majority of isolates were cultured from urine (297, 96.1%). Blood cultures comprised 11 cases (3.6%). The majority of ESBL cultures were collected in an outpatient setting; 15% were collected from hospital inpatients and fewer than 5% from residents of a long-term care facility (LTCF) or long-term acute care hospital (LTACH). However, 21% of those collected in an outpatient setting, primarily the ED, were hospitalized within 30 days. Over 60% of the cases had at least one relevant risk factor documented in their medical record. One-third had documented antimicrobial use in the prior month, 39% had been hospitalized in the year prior, and 19% had a urinary catheter in place in the 2 days prior to culture collection. Interestingly, while only 2% had documentation of international travel in the two months prior to culture, 18% had either documented international travel outside of that timeframe, or required the use of language interpretation, possibly indicating extensive time living internationally in the past. Conclusion Among residents of Bernalillo County, NM, ESBL isolates were predominantly E. coli, cultured from urine in outpatient settings. Over half had documentation of recognized risk factors, including prior hospitalizations, recent antibiotic use, or presence of indwelling devices. Disclosures All authors: No reported disclosures.