Background: Previous analyses describing the relationship between SARS-CoV-2 infection and Staphylococcus aureus have focused on hospital-onset S. aureus infections occurring during COVID-19 hospitalizations. Because most invasive S. aureus (iSA) infections are community-onset (CO), we characterized CO iSA cases with a recent positive SARS-CoV-2 test (coinfection). Methods: We analyzed CDC Emerging Infections Program active, population- and laboratory-based iSA surveillance data among adults during March 1–December 31, 2020, from 11 counties in 7 states. The iSA cases (S. aureus isolation from a normally sterile site in a surveillance area resident) were considered CO if culture was obtained <3 days after hospital admission. Coinfection was defined as first positive SARS-CoV-2 test ≤14 days before the initial iSA culture.  We explored factors independently associated with SARS-CoV-2 coinfection versus no prior positive SARS-CoV-2 test among CO iSA cases through a multivariable logistic regression model (using demographic, healthcare exposure, and underlying condition variables with P<0.25 in univariate analysis) and examined differences in outcomes through descriptive analysis. Results: Overall, 3,908 CO iSA cases were reported, including 138 SARS-CoV-2 coinfections (3.5%); 58.0% of coinfections had iSA culture and the first positive SARS-CoV-2 test on the same day (Fig. 1). In univariate analysis, neither methicillin resistance (44.2% with coinfection vs 36.5% without; P = .06) nor race and ethnicity differed significantly between iSA cases with and without SARS-CoV-2 coinfection (P = .93 for any association between race and ethnicity and coinfection), although iSA cases with coinfection were older (median age, 72 vs 60 years , P<0.01) and more often female (46.7% vs 36.3%, P=0.01).  In multivariable analysis, significant associations with SARS-CoV-2 coinfection included older age, female sex, previous location in a long-term care facility (LTCF) or hospital, presence of a central venous catheter (CVC), and diabetes (Figure 2).  Two-thirds of co-infection cases had ≥1 of the following characteristics: age > 73 years, LTCF residence 3 days before iSA culture, and/or CVC present any time during the 2 days before iSA culture. More often, iSA cases with SARS-CoV-2 coinfection were admitted to the intensive care unit ≤2 days after iSA culture (37.7% vs 23.3%, P<0.01) and died (33.3% vs 11.3%, P<0.01). Conclusions: CO iSA patients with SARS-CoV-2 coinfection represent a small proportion of CO iSA cases and mostly involve a limited number of factors related to likelihood of acquiring SARS-CoV-2 and iSA. Although CO iSA patients with SARS-CoV-2 coinfection had more severe outcomes, additional research is needed to understand how much of this difference is related to differences in patient characteristics.

Disclosures: None

Background: The Canadian Nosocomial Infection Surveillance Program (CNISP) observed increased mortality among neonatal intensive care unit (NICU) patients with central-line–associated bloodstream infection (CLABSI) starting in 2017. In this study, we compared NICU patients with CLABSIs before and after 2017, and quantified the impact of epidemiological factors on 30-day survival. Methods: We included 1,276 NICU patients from 8–16 participating CNISP hospitals from the pre-2017 period (2009–2016) and the post-2017 period (2017–2022) using standardized definitions and questionnaires. We used Cox regression modeling to assess the impact of age at date of positive culture, sex, birthweight, CLABSI microorganism, region of the country, and surveillance period (before 2017 vs after 2017) on time to 30-day all-cause mortality from date of positive culture. Gestational age was not available for this analysis. We reported model outputs as hazard ratios with 95% CIs. Results: In total, 769 (60%) NICU CLABSIs were reported in the pre-2017 period and 507 (40%) in the post-2017 period. The 30-day all-cause mortality rate was 8% (n = 100 of 1,276) overall, and significantly higher after 2017 (12%, n = 61 of 507) than before 2017 (5%, n = 39 of 769) (P < .001).

During the post-2017 period, cases were significantly younger: 16 days (IQR, 9–33) versus 21 days (IQR, 11–49) (P = .002). Median days from ICU admission to infection were shorter: 14 (IQR, 8–31) versus 19 (IQR, 10–41) (P < .001). More gram-negative CLABSIs were identified (29% vs 24%; P = .040) and fewer gram-positive CLABSIs were identified (64% vs 72%; P = .006) compared to the pre-2017 period. Mortality was higher in CLABSIs caused by gram-negative bacteria (15%, n = 50 of 328) than gram-positive bacteria (4.4%, n = 39 of 877) (P < .001), and mortality was higher in neonates with birthweight <1,000 g (11%, n = 71 of 673) compared to those weighing ≥1,000 g (5%, n = 28 of 560) (P < .001).

Adjusting for all other factors, survival modeling indicated that NICU CLABSIs identified in the post-2017 period had 2.12 (95% CI, 1.23–3.66) times the hazard ratio of 30-day all-cause mortality compared to those before 2017 (P < .006). Those identified with a gram-positive bacterium had a 0.28 hazard ratio (95% CI, 0.12–0.65) of 30-day mortality compared to those with a gram-negative bacterium or fungus (P = .003). In the fully adjusted model, age, sex, and birthweight were not significantly associated with NICU CLABSI survival. Conclusions: NICU patients with CLABSIs had significantly higher all-cause mortality between 2017–2022 compared to 2009–2016, and those who acquired gram-positive–associated CLABSIs had improved survival compared to other organisms. Further work is needed to identify and understand factors driving the increased mortality among NICU CLABSI patients from 2017–2022.

Disclosures: None

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

OBJECTIVES/GOALS: Approximately 37 million people in the U.S. have chronic kidney disease, which is a major risk factor for cardiovascular and end stage renal diseases. PPAR-αknockout (KO) mice exhibit increased renal inflammation and blood pressure. In this study, we investigated the role of PPAR-αin renal function in a mouse model of hypertension. METHODS/STUDY POPULATION: Male 4-month-old wild type (WT) and PPAR-αKO mice were instrumented with radio transmitters by artery canulation (Data Science Intl). This method minimizes stress and artifacts by avoiding the use of tethering, restraining, or anesthetizing the mice during data sampling. After recovery from surgery, we continuously measured mean arterial pressure (MAP) via radio telemetry in conscious ambulatory mice. After baseline MAP was established, vehicle (Veh; saline) or angiotensin II (Ang II) were infused using an osmotic minipump at a slow pressor dose (400 ng/kg/min) for 12 days. On day 12, we injected an intravenous bolus of fluorescin-sinistrin (3.74µl/g body weight) and collected 8 blood samples (20µl/sample) over 75 minutes to enable calculation of the glomerular filtration rate (GFR) using [GFR = I/(A/α+ B/ß)]. RESULTS/ANTICIPATED RESULTS: Similar to our prior observations, no significant (ns) differences in baseline MAP were observed between WT and PPAR-αKO mice [(mmHg): WT (n=6), 111 ± 20 vs. PPAR-αKO (n=6), 113 ± 10; ns] whereas after 12 days of the slow pressor effect of Ang II, MAP was increased in both strains [(mmHg): WT (n=8), 138 ± 11# vs. PPAR-αKO (n=8) , 156 ± 16#; #p DISCUSSION/SIGNIFICANCE: PPAR-αprotects mice from worsening hypertension and is critical to preserving GFR during normotensive conditions. Ongoing studies are further investigating how PPAR-αregulates renal function. These finding suggest therapeutics designed to increase PPAR-αactivity could have clinical benefit in chronic kidney disease.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

OBJECTIVES/GOALS: The SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2), which underlies the current COVID-19 pandemic, among other tissues, also targets the central nervous system (CNS). The goal of this study is to investigate mechanisms of neuroinflammation in Lipopolysaccharides (LPS)-treated mouse model and SARS-CoV-2-infected hamsters. METHODS/STUDY POPULATION: In this research I will assay vascular reactivity of cerebral vessels to assess vascular dysfunction within the microcirculation. I will determine expression of proinflammatory cytokines, coagulation factors and AT1 receptors (AT1R) in isolated microvessels from the circle of Willis to assess inflammation, thrombosis and RAS activity in the microvasculature. LPS and SARS-CoV-2, are both associated with coagulopathies and because of that I will measure concentration of PAI-1, von Willebrand Factor, thrombin and D-dimer to assess the thrombotic pathway in the circulation. Histology and immunohistochemistry will assess immune cell type infiltration into the brain parenchyma, microglia activation and severity of neuroinflammation and neural injury. RESULTS/ANTICIPATED RESULTS: We hypothesize that under conditions of reduced ACE2 (e.g., SARS-CoV-2 infection), AT1R activity is upregulated in the microvasculature. In the presence of an inflammatory insult, these AT1Rs promote endothelialitis and immunothrombosis through pro-thrombotic pathways and pro-inflammatory cytokine production leading to endothelial dysfunction in the microvasculature, blood brain barrier (BBB) injury, deficits in cognition and increased anxiety. We will test this hypothesis through 2 aims: Aim 1: Determine the role of the pro-injury arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. Aim 1: Determine the role of the protective arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. DISCUSSION/SIGNIFICANCE: This study will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19. This research is a necessary first step in understanding mechanisms of brain pathogenesis that can set the groundwork for future studies of more complex models of disease.

Background: This review describes the epidemiology of carbapenemase-producing organisms (CPO) in both the community and hospitalized populations in the province of Alberta. Methods: Newly identified CPO-positive individuals from April 1, 2013, to March 31, 2018, were retrospectively reviewed from 3 data sources, which shared a common provincial CPO case definition: (1) positive CPO results from the Provincial Laboratory for Public Health, which provides all referral and confirmatory CPO testing, (2) CPO cases reported to Alberta Health, and (3) CPO surveillance from Alberta Health Services Infection Prevention and Control (IPC). The 3 data sources were collated, and initial CPO cases were classified according to their likely location of acquisition: hospital-acquired, hospital-identified, on admission, and community-identified. Risk factors and adverse outcomes were obtained from linkage to administrative data. Results: In total, 171 unique individuals were newly identified with a first-time CPO case. Also, 15% (25 of 171) were hospital-acquired (HA), 21% (36 of 171) were hospital-identified (HI), 33% (57 of 171) were on admission, and 31% (53 of 171) were community identified. Overall, 9% (5 of 171) resided in long-term care facilities. Of all patients in acute-care facilities, 30% (35 of 118) had infections and 70% were colonized. Overall, 38% (65 of 171) had an acute-care admission in the 1 year prior to CPO identification; 59% (63 of 106) of those who did not have a previous admission had received healthcare outside Alberta. A large proportion of on-admission cases (81%, 46 of 57) and community-identified (66%, 33 of 53) cases did not have any acute-care admissions in Alberta in the previous year. Overall, 10% (14 of 171) had ICU admissions in Alberta within 30 days of CPO identification, and 5% (8 of 171) died within 30 days. The most common carbapenemase gene identified was NDM-1 (53%, 90 of 171). Conclusions: These findings highlight the robust nature of Alberta’s provincial CPO surveillance network. We reviewed 3 different databases (laboratory, health ministry, IPC) to obtain comprehensive data to better understand the epidemiology of CPO in both the community and hospital settings. More than half of the individuals with CPO were initially identified in the community or on admission. Most had received healthcare outside Alberta, and no acute-care admissions occurred in Alberta in the previous year. It is important to be aware of the growing reservoir of CPO outside the hospital setting because it could impact future screening and management practices.

Funding: None

Disclosures: None

Background: The association between antimicrobial use (AMU) and emergence of antimicrobial resistance is well documented. The Canadian Nosocomial Infection Surveillance Program (CNISP) has conducted sentinel surveillance of AMU at participating Canadian hospitals since 2009 resulting in the largest pan-Canadian hospital database of dispensed antimicrobials. Objectives: Describe interhospital variability of AMU across Canada. Methods: Hospitals submit annual AMU data based on patient days (PD). Antimicrobials were measured in defined daily doses (DDD) for adults using the WHO Anatomical Therapeutic Chemical (ATC) system. The AMU data among pediatric patients have been available since 2017 using days of therapy (DOT). Surveillance includes systemic antibacterial agents (J01 ATC codes), oral metronidazole, and oral vancomycin. AMU was assessed using quintiles, interquartile ranges (IQR), and relative IQRs (upper- and lower-quartile values divided by the median). Results: Between 2009 and 2018, 20–26 hospitals participated in adult surveillance each year (35 teaching hospitals and 3 nonteaching hospitals participated in ≥1 year). Over this period, overall AMU decreased by 13% at participating adult hospitals from 645 to 560 DDD per 1,000 PD. AMU varied substantially between hospitals, but this variability decreased over time (Fig. 1). In 2009, the IQRs for overall AMU spanned 309 DDD per 1,000 PD, and in 2018 it spanned only 103 DDD per 1,000 PD. This decrease in variability was due to large decreases in use among hospitals with high use in 2009–2010. Among hospitals in the highest use quintile in 2009–2010, AMU decreased, on average, 44 DDD per 1,000 PD each year. Among hospitals in the lowest use quintile in 2009–2010, AMU increased, on average, 6 DDD per 1,000 PD each year. In 2018, antibiotics with the largest absolute IQR variability were cefazolin (61–113 DDD per 1,000 PD), piperacillin-tazobactam (32–64 DDD per 1,000 PD), and vancomycin (24–49 DDD per 1,000 PD). Among antibiotics with ≥1 DDD per 1,000 PD, antibiotics with the largest relative IQR variability were tobramycin (0.3–6 DDD per 1,000 PD), cefadroxil (0.08–9 DDD per 1,000 PD), and linezolid (0.2–3 DDD per 1,000 PD). In 2018, the IQR for overall pediatric AMU (n = 7 teaching hospitals) was 426–581 DOT per 1,000 PD. Antibiotics with the largest IQRs were vancomycin (0.6–58 DOT per 1,000 PD), cefazolin (33–88 DOT per 1,000 PD), and tobramycin (3–57 DOT per 1,000 PD). Among antibiotics with ≥1 DOT per 1,000 PD in 2018, antibiotics with the largest relative IQRs were tobramycin (3–57 DOT per 1,000 PD), cefuroxime (1–6 DOT per 1,000 PD), and amoxicillin (8–42 DOT per 1,000 PD). Conclusions: There is wide variation in overall antibiotic use across hospitals. Variation between AMU at adult hospitals has decreased between 2009 and 2018; in 2018, antibiotics with the largest IQRs were cefazolin and piperacillin-tazobactam. Benchmarking AMU is crucial for informing antimicrobial stewardship efforts.

Funding: CNISP is funded by the Public Health Agency of Canada.

Disclosures: Allison McGeer reports funds to her institution from Pfizer and Merck for projects for which she is the principal investigator. She also reports consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were >2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P < .001), included more females (56.4% vs 50.9%; P < .001), and were more often treated with metronidazole (63.0% vs 56.1%; P < .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.

Funding: None

Disclosures: Susy Hota reports contract research for Finch Therapeutics.

Background: Nosocomial central-line–associated bloodstream infections (CLABSIs) are an important cause of morbidity and mortality in hospitalized patients. CLABSI surveillance establishes rates for internal and external comparison, identifies risk factors, and allows assessment of interventions. Objectives: To determine the frequency of CLABSIs among adult patients admitted to intensive care units (ICUs) in CNISP hospitals and evaluate trends over time. Methods: CNISP is a collaborative effort of the Canadian Hospital Epidemiology Committee, the Association of Medical Microbiologists and Infectious Disease Canada and the Public Health Agency of Canada. Since 1995, CNISP has conducted hospital-based sentinel surveillance of healthcare-associated infections. Overall, 55 CNISP hospitals participated in ≥1 year of CLABSI surveillance. Adult ICUs are categorized as mixed ICUs or cardiovascular (CV) surgery ICUs. Data were collected using standardized definitions and collection forms. Line-day denominators for each participating ICU were collected. Negative-binomial regression was used to test for linear trends, with robust standard errors to account for clustering by hospital. We used the Fisher exact test to compare binary variables. Results: Each year, 28–42 adult ICUs participated in surveillance (27–37 mixed, 6–8 CV surgery). In both mixed ICUs and CV-ICUs, rates remained relatively stable between 2011 and 2018 (Fig. 1). In mixed ICUs, CLABSI rates were 1.0 per 1,000 line days in 2011, and 1.0 per 1,000 line days in 2018 (test for linear trend, P = .66). In CV-ICUs, CLABSI rates were 1.1 per 1,000 line days in 2011 and 0.8 per 1,000 line days in 2018 (P = .19). Case age and gender distributions were consistent across the surveillance period. The 30-day all-cause mortality rate was 29% in 2011 and in 2018 (annual range, 29%–35%). Between 2011 and 2018, the percentage of isolated microorganisms that were coagulase-negative staphylococci (CONS) decreased from 31% to 18% (P = .004). The percentage of other gram-positive organisms increased from 32% to 37% (P = .34); Bacillus increased from 0% to 4% of isolates and methicillin-susceptible Staphylococcus aureus from 2% to 6%). The gram-negative organisms increased from 21% to 27% (P = .19). Yeast represented 16% in 2011 and 18% in 2018; however, the percentage of yeast that were Candida albicans decreased over time (58% of yeast in 2011 and 30% in 2018; P = .04). Between 2011 and 2018, the most commonly identified species of microorganism in each year were CONS (18% in 2018) and Enterococcus spp (18% in 2018). Conclusions: Ongoing CLABSI surveillance has shown stable rates of CLABSI in adult ICUs from 2011 to 2018. The causative microorganisms have changed, with CONS decreasing from 31% to 18%.

Funding: CNISP is funded by the Public Health Agency of Canada.

Disclosures: Allison McGeer reports funds to her for studies, for which she is the principal investigator, from Pfizer and Merck, as well as consulting fees from Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

Early institutional rearing is associated with increased risk for subsequent peer relationship difficulties, but the underlying mechanisms have not been identified. Friendship characteristics, social behaviors with peers, normed assessments of social problems, and social cue use were assessed in 142 children (mean age = 10.06, SD = 2.02; range 7–13 years), of whom 67 were previously institutionalized (PI), and 75 were raised by their biological families. Anxiety and attention-deficit/hyperactivity disorder (ADHD) symptoms, often elevated among PI children, were examined as potential mediators of PI status and baseline social functioning and longitudinal follow-ups (2 and 4 years later). Twenty-seven percent of PI children fell above the Child Behavior Checklist Social Problems cutoff. An examination of specific social behaviors with peers indicated that PI and comparison children did not differ in empathic concern or peer social approach, though parents were more likely to endorse aggression/overarousal as a reason that PI children might struggle with friendships. Comparison children outperformed PI children in computerized testing of social cue use learning. Finally, across these measures, social difficulties exhibited in the PI group were mediated by ADHD symptoms with predicted social problems assessed 4 years later. These findings show that, when PI children struggle with friendships, mechanisms involving attention and behavior regulation are likely contributors.