bluuebunny/crossref_metadata_2025_split huggingface dataset:
985. Pooled RNA Metagenomics to Enable Scalable, Unbiased Pathogen Detection and Surveillance
Authors: Messer Katelyn S , Adams Gordon , Paull Jillian S , Livny Jonathan , Lemieux Jacob , Park Daniel J , Sabeti Pardis C , Siddle Katherine J 
Published: November 2023

Abstract

Background
As disease patterns shift with changing demographics and climate, developing comprehensive and scalable tools for tracking and identifying emerging pathogens is an increasingly critical component in mounting a robust public health response. Metagenomic next-generation sequencing (mNGS) provides unbiased detection of etiological agents from diverse types of clinical specimen and has great potential to aid in the prediction and prevention of future outbreaks. However, available protocols are unsuitable for widespread and routine use, due to high cost and extended hands-on time required for sample processing. Thus there is a need for faster, cheaper, and more automatable sequencing methods that retain the accuracy and breadth of current protocols.

Methods
Here we develop Pooled RNA Metagenomics; a cost-effective and highly-multiplexed method that accelerates the processing of RNA samples by barcoding individual samples early in the pipeline allowing for parallel preparation. We benchmark this method by comparing the output from clinical samples to that from other established mNGS methods. Additionally, the protocol is designed to preserve the RNA sense information in the resulting sequencing data, and we incorporate unique molecular identifiers upstream of amplification; two features that enhance the utility and flexibility of the method for downstream applications.
Pooled RNA Metagenomics Overview
Schematic overview of the pooled mNGS workflow: RNA samples are ligated to uniquely barcoded adapters before being pooled together for cDNA synthesis with UMI incorporation and subsequent library construction PCR.

Results
We found that early pooling of barcoded RNA samples can reduce reagent costs by up to 80% and processing time by up to 60%. We demonstrate that pooling up to 32 samples in a single well results in similar recovery of complete viral genomes to those produced by other mNGS methods where each RNA is processed separately.

Conclusion
Pooled RNA Metagenomics provides an innovative, cost-effective, scalable, and pathogen-agnostic approach to outbreak monitoring and prevention. The high throughput enabled by this method can be augmented by incorporating automation, which in tandem increases speed and scale. The protocol is also amenable to miniaturization, which can further reduce costs and is of particular interest for low input clinical specimens. In summary, Pooled RNA Metagenomics dramatically lowers the barrier to high throughput mNGS, making it a viable option for enhanced pathogen surveillance.

Disclosures
Pardis C. Sabeti, MD, PhD, Danaher Corp: Board Member|Danaher Corp: Stocks/Bonds|Delve Bio: Advisor/Consultant|Delve Bio: Stocks/Bonds|NextGen Jane: Advisor/Consultant|Sherlock Biosciences, Inc: Advisor/Consultant|Sherlock Biosciences, Inc: Stocks/Bonds
1034. COVID-19 Bloodstream Infection Outcomes Stratified by Social Determination Index (SDI) in NYC Public Hospital System
Authors: Yao Lim Chee , Johan Kenneth , Gutierrez Jorge , Romero Garcia Alberto , Afzal Afsheen , Al-Khateeb Mohannad Al-Khateeb , Yankulova Boyana , Yusuf Mubarak , De Castro Yinelka Silverio , Venugopal Usha , Feinstein Addi , La Fortune Alexander , Sittler Daniel , Menon Vidya 
Published: November 2023

Abstract

Background
Impact of socioeconomic factors on outcomes was significant during the COVID-19 pandemic. We aim to study disparities in outcomes among hospitalized COVID-19 patients with bloodstream infection (BSI) stratified by SDI in the NYC Public Health System.

Methods
Retrospective multicenter study of hospitalized patients with COVID-19 in 11 acute care hospitals in the NYC public health system from March 2020 to May 2020 was collected. Hospitals are further stratified according to the median household income of NYC using their zip code area into high (≥$65,000), medium ($40,000-64,999) and low income (&lt; $40,000). Descriptive statistics were used to compare baseline patient characteristics including COVID-19 severity and BSI features. The primary outcome was in-hospital mortality. Logistic regression models were used to adjust for potential confounders.
Inclusion Process of Study Population

Results
Eleven hospitals were stratified based on SDI (high income: 2, medium income: 4, low income: 3), 2 were excluded as they lie on zip codes with overlapping income. Patients’ baseline and BSI characteristics are described in Table 1. For every change in income group: high-middle and middle-low, the odds of mortality increased by 1.33 times (p=0.048). Additionally, for every increase in 1 year of age above 23, the risk of mortality from BSI increased by 2.2% (p=0.004).
Baseline Characteristics of Subjects Stratified by Household Income Status
Bloodstream Infection Characteristics Stratified by Household Income Status

Conclusion
The study shows the impact of health disparities during COVID-19 among hospitals with the same standard of care, where higher mortality rates were observed in low and middle-income zip code areas in NYC, likely due to the burden of social determinants of health. Hospital acquired BSI was uniformly high in all income groups, compared to primary BSI. Nonetheless, it provided an insight about the need for further investigation about the impact of socioeconomic factors on mortality and for strategies to address disparities in access to healthcare.

Disclosures
All Authors: No reported disclosures
1103. Endemic Coronavirus Infections in a US Cohort of Children from Birth to 4 Years
Authors: Payne Daniel C , Morrow Ardythe L , Conrey Shannon C , McMorrow Meredith L , McNeal Monica , Niu Liang , Burrell Allison , Schlaudecker Elizabeth P , Mattison Claire , Burke Rachel M , DeFranco Emily A , Teoh Zheyi , Wrammert Jens , Atherton Lydia J , Thornburg Natalie J , Staat Mary A 
Published: November 2023

Abstract

Background
Endemic coronaviruses (“CoVs”) OC43, HKU1, NL63 and 229E are “common cold viruses” related to SARS-CoV-2, but their natural histories are poorly understood. We documented endemic CoV infections in a prospective cohort of US infants and children to determine the extent to which natural infection protects against subsequent homotypic and heterotypic endemic CoV infections and SARS-CoV-2 infections.

Methods
Cincinnati mother-child pairs were enrolled in the third trimester of pregnancy in 2017-18 and children were followed from birth to 4 years with weekly collection of mid-turbinate nasal swabs. Blood was collected at 6 weeks; 6, 12, 18, 24 months; and annually thereafter. Mothers reported on socio demographics, risk factors, and the child’s weekly symptoms. Medical visits were documented from pediatric care providers.
CoV infections were followed for the first 4 years of life (focusing on the most compliant subset of 116 children having &gt;70% weekly sample collection). Infections were identified through nasal swabs tested using a RT-PCR multiplex pathogen panel, and by serum IgG responses using a validated kit at CDC and interpreted using classification and regression tree (CART) analysis.

Results
We detected 398 endemic CoV infections over 317.5 child-years of follow-up (1.1 infections/child-year). Endemic beta-coronaviruses, OC43 and HKU1, were associated with statistically significant homotypic protection (77% and 84%, respectively) after a single infection. Similarly protective homotypic associations (73%) were elicited by NL63, the dominant alpha-coronavirus, after two infections. 229E infections were uncommon. No heterotypic protective association was found for any of the endemic CoVs or for SARS-CoV-2 infections from June 2020 to Nov 2021. The majority of endemic CoVs and SARS-CoV-2 infections were asymptomatic, but this proportion varied by CoV strain. Symptomatic infections were mild for all CoV strains with no hospitalizations.

Conclusion
Natural infection resulted in homotypic immunity but not heterotypic immunity against other CoVs to the 4th birthday. Children were not protected against SARS-CoV-2 by prior endemic CoV infections. CoV infections in these young children were largely asymptomatic or mild.

Disclosures
Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
1931. Real-world evaluation of adequacy of empiric and definitive therapy in carbapenem susceptible and non-susceptible Enterobacterales and Pseudomonas aeruginosa by time to culture result: A multicenter analysis
Authors: Riccobene Todd , Ai ChinEn , Yu Kalvin , Gregory Sara , Lock John L , Kim Brooke , Gupta Vikas 
Published: November 2023

Abstract

Background
Infections caused by multi-drug resistant (MDR) Gram-negative pathogens are increasingly problematic in healthcare settings and are associated with worse clinical outcomes in critically ill patients. We conducted a multicenter real-world evaluation of culture turn-around time (TAT), associated inadequate empiric (IET) and definitive therapy (IDT) in carbapenem susceptible (Carb-S) and non-susceptible (Carb-NS) Enterobacterales (ENT) and P. aeruginosa (PSA).

Methods
Hospitalized adults (≥ 18 years old) with facility reported antibiotic susceptibility from 2018-2022 across 161 facilities (BD Insights Research Database, Franklin Lakes, NJ) were identified for non-contaminant Carb-S/Carb-NS ENT and PSA across respiratory, blood, urine, intra-abdominal, skin/wound, and other sources. We evaluated antibacterial therapy as IET (prior to first susceptibility result) and IDT (48hrs post first susceptibility result & not discharged) by culture TAT (date/time first susceptibility results – date/time culture collection).

Results
We identified 345,245 ENT of which 1.8% (6,174) were Carb-NS and 60,143 PSA of which 17.2% (10,357) were Carb-NS. IDT was lower than IET in Carb-S ENT (12.9% vs. 5.1%), Carb-NS ENT (53.5% vs. 25.2%), Carb-S PSA (28.4% vs. 11.0%), and Carb-NS PSA (53.5% vs. 26.0%) pathogen results. IDT was also lower than IET at each 12-hour increment of availability of susceptibility results (Figure 2) and overall IDT was 25.2% and 26.0% in Carb-NS ENT and Carb-NS PSA, respectively. Median time to positive susceptibility result was longer in Carb-NS ENT vs. Carb-S ENT (67 vs. 53 hrs) and longer in Carb-NS PSA vs. Carb-S PSA (68 vs. 62 hrs) (Table 1, Figure 1).

Conclusion
There was a reduction in inadequate therapy prescribed once cultures were available (IET to IDT) overall and across each of the 12-hr TAT to susceptibility results periods evaluated in Carb-S and Carb-NS ENT and PSA positive cases. Both IET and IDT were higher in patients with either Carb-NS ENT or Carb-NS PSA than Carb-S patients. However, more than 25% of patients with Carb-NS ENT/PSA were prescribed IDT within 48 hours of a susceptibility result. These data support efforts to improve TAT to susceptibility results and can inform protocols and workflow that guide empiric and definitive therapy.

Disclosures
Todd Riccobene, PhD, AbbVie: Employee salary|AbbVie: Stocks/Bonds ChinEn Ai, MPH, Becton, Dickinson and Company: Employee Kalvin Yu, MD, FIDSA, BD: Stocks/Bonds Sara Gregory, PhD, Becton, Dickinson and Company: Employee John L. Lock, PharmD, AbbVie: Employee|AbbVie: Stocks/Bonds Brooke Kim, RN, BSN, MSM, AbbVie: Employee|AbbVie: Stocks/Bonds Vikas Gupta, PharmD, Becton, Dickinson and Company (BD): Employee of BD|Becton, Dickinson and Company (BD): Stocks/Bonds
1181. Evaluation of the Safety of a Beta-Lactam Allergy Protocol
Authors: Sakowski Alexandra K , Borkowski Jaime , Rhodes Karen 
Published: November 2023

Abstract

Background
Beta-lactam allergies (BLA) pose a challenge to the optimization of antibiotic therapy as some of these are not true allergies, are minor reactions, or instead may be adverse effects. This issue is further complicated by the fact that traditional methods of challenging allergies can be costly or time-consuming. The purpose of this study was to evaluate the safety of a protocol which directly challenges patients with a BLA via full dose administration of the challenge antibiotic based on the risk of cross-reactivity.

Methods
This retrospective, observational, case-control study compared the incidence of hypersensitivity reactions following the administration of a beta-lactam antibiotic in patients with a reported BLA to that of those without a reported BLA. It included adults in the community hospital setting who received a beta-lactam antibiotic for any indication during an inpatient admission between March 2018 and October 2022. The treatment groups were separated by the presence or absence of a documented BLA. The primary outcome was the occurrence of a hypersensitivity reaction following the administration of a beta-lactam antibiotic.

Results
A total of 910 out of 1000 patients were eligible for evaluation, and 116 of those patients had a history of a BLA documented on the chart whereas 794 did not. The primary outcome of an IgE-mediated hypersensitivity reaction occurred in 1 out of 116 in the BLA group and 4 out of 794 in the non-BLA group (OR 1.72; 95% CI 0.19-15.5) (see table).
Results

Conclusion
No significant increase in the incidence of IgE-mediated allergic reactions was noted in the patients with a history of a BLA, however, the study was not powered to detect a difference due to the rarity of IgE-mediated reactions. Despite a trend towards an increased risk of reactions in patients with a history of a BLA, the majority of the few reactions that occurred were non-severe in nature. The benefits of challenging a BLA outweigh the risks in this setting.

Disclosures
All Authors: No reported disclosures
1187. Evaluation of an Antimicrobial Stewardship (AS) Bundle for Uncomplicated Gram-Negative Bloodstream Infections (GN-BSI) in Adults at a Large Academic Health System
Authors: Dipietro Juliana M , Dubrovskaya Yanina , Marsh Kassandra , Decano Arnold , Mazo Dana , Major Vincent J , So Jonathan , Yuditskiy Samuel , Papadopoulos John , Siegfried Justin 
Published: November 2023

Abstract

Background
AS bundles provide concise steps to clinicians at the point of care to guide antibiotic decision-making. At NYULH GN-BSI bundle was implemented in the electronic health record of the microbiology report. The purpose of this project was to evaluate the impact of the bundle on patient outcomes and prescribing.

Methods
This was a multicenter, retrospective review of patients with GN-BSI in the pre-bundle group (preBG, 3/2019-2/2020) and post-bundle group (postBG, 3/2021 to 2/2022). The primary outcome was the composite of in-hospital mortality, infection-related readmission, and GN-BSI recurrence.

Results
Out of 1097 patients screened, 225 patients met inclusion criteria n=101 in preBG, n=124 in postBG. Baseline characteristics were similar between groups, including Charlson Comorbidity Index [4 (IQR 3-6) vs. 4 (2-5); p=NS] and Modified PITT Bacteremia Score [1 (0-2) vs. 1 (0-2); p=NS]. The most common sources of GN-BSI were urinary (59 vs 59%, p=NS) and intra-abdominal (29 vs 23%, p=NS). E. coli (62 vs 61% p=NS) and K. pneumoniae (30 vs 21%, p=NS) were the most common organisms. There was no difference in the primary composite outcome (13 vs 7%; p=NS) and its individual components of in-hospital mortality, 30-day infection related readmission and GN-BSI recurrence (2 vs 0%, 10 vs 7%, 1 vs 1.6%). The median hospital length of stay (HLOS) from GN-BSI onset and days of therapy were also similar between the pre- and postBG [5 vs 5 days, p=NS; 14 vs 15 days, p=NS]. There was no difference between pre- and postBG in empiric vancomycin (VAN) initiation (57 vs 61%) and median VAN days (2 vs. 2 days). VAN discontinuation (DC) was done more frequently by the primary team in postBG group (67 vs. 38% preBG; p&lt; 0.01). Numerically more patients were de-escalated in postBG (81 vs 73% preBG, p=NS) with 9% increase in the use of ampicillin/sulbactam or amoxicillin/clavulanate, p=0.043 and no difference in time to de-escalation. In postBG, de-escalation by the primary team and ASP increased numerically by 8.8%, p=NS and 4.4%, p=NS with a decrease in ID recommendations related to de-escalation by 13.6%, p=NS.

Conclusion
GN-BSI bundle worked as a nudge-based tool to guide providers in VAN DC, de-escalation to more narrow antibiotics and decreasing amount of ID consults without negative impact on HLOS and patient outcomes.

Disclosures
All Authors: No reported disclosures
1189. The Impact of Clinical Staff Pharmacist Driven Weekend Antimicrobial Stewardship Coverage in a Quaternary Hospital in UAE
Authors: Elrefaei Hazem , Al Quteimat Osama , Ismail Rami , Nasef Rama , Hisham Mohamed , El Nekidy Wasim S , ElLababidi Rania 
Published: November 2023

Abstract

Background
Pharmacy antimicrobial stewardship services were extended to cover the weekends, incorporating a clinical staff pharmacist with infectious disease (ID) training to cover antimicrobial stewardship program (ASP) activities on weekends is an opportunity. The aim of this study is to assess the impact of integration ASP clinical staff pharmacist into an ASP on weekends by collecting and analyzing the documented pharmacists’ ASP interventions before and after implantation of the service.

Methods
A single center, pre-post quasi-experimental study. Data were collected retrospectively from the electronic medical record (EMR). The study included at 2 sets of data: pre-implementation (2020) and post-implementation (2021) of an ASP weekend pharmacist,
The primary outcome is to evaluate pharmacist ASP Interventions through prospective audit and feedback review analysis. Secondary outcomes include antibiotics days of therapy (DOT), length of hospital stay (LOS), healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 1:Characteristics of the pre-and post-intervention group

Results
During the study, an increase in the number of documented interventions was observed with 452 interventions were documented on 362 patients during the post-implementation period compared to 114 interventions were documented on 108 patients during the pre-implementation period (p = 0.04).
A reduction in the LOS was observed with a median (IQR) of 16 days (8-34) during the post-implementation period compared to 27.5 days (10-56) during the pre-implementation period (p = 0.001), while the median (IQR) total DOT was increased during the post-implementation period 8 (6-11) versus 7 (4-11) during the pre-implementation period (p = &lt; 0.001). No differences were observed in healthcare associated Clostridioides difficile infection (CDI) and infection-related readmission.Table 2:Pharmacist interventions on the pre-and post-intervention groupTable 3:Outcome of pharmacists driven weekend antimicrobial stewardship on the pre-and post-intervention group

Conclusion
The pharmacists driven weekend antimicrobial stewardship is an opportunity for the pharmacists to intervene and optimize patients’ treatment plan and contributed towards a significant shortened length of hospital stay. Therefore, healthcare facilities should prioritize the involvement of pharmacists in weekend ASPs to ensure consistent, high-quality care throughout the week.

Disclosures
All Authors: No reported disclosures
1203. Impact of Antimicrobial Stewardship Interventions on Hospital-Onset Clostridioides difficile Infections
Authors: Kwon Taesung , Dillon Caroline E , Duggirala Madhuri , Berk Daniel , Barbour Tyler , Vasireddy Swati , Yablonski Bridget , Shelly Mark A 
Published: November 2023

Abstract

Background
We carried out a case control study to document the effect of antimicrobial stewardship interventions (ASI) on hospital-onset CDI.
Types of antimicrobial stewardship intervention and implementation rate
*Antimicrobial stewardship team reviews the case and recommends no change.

Methods
We identified cases of laboratory-identified CDI at a medical school-affiliated medical center. Cases were identified by PCR as laboratory identified hospital onset CDI. Each case was matched with 2 cases where a stool PCR on the same hospital day was negative in the same month. Cases were limited to adults without a history of CDI in the last 3 months. Charts were reviewed for CDI risk factors, antibiotic exposure, and ASI documentation and follow-through.

Results
From 2020 to 2021 there were 145 cases of HO-CDI, for which we assigned 125 cases with 250 in the matched referent group. A total of 323 ASIs were recorded in 184 charts. The ASI implementation rate was 87.2% with the lowest rate (77%) seen in “discontinue antibiotics” (Table). Of patients in the CDI group, 53.6% (67) had an ASI, compared to 47.2% (118) in the control (OR 1.29 (0.84 to 1.99), P = 0.25). Oftentimes (47.8%) these occurred on or after the day of the CDI test. Most risk factors for CDI were evenly distributed in both groups. Use of PPI/H2 blockers were seen more often in the cases (73.6% in cases vs 58.4% in controls, OR 2.00 (1.26 to 3.23), P = 0.004). The number of days with antibiotics and the cumulative number of antibiotic days was not different in patients tested for CDI. The median (IQR) of the number of days with antibiotic use in the 30 days prior to test was 6 (3.5 to 9) in the CDI and 7 (4 to 10) in the control. The total number of antibiotic days were 9 (5 to 14) in the CDI group and 10 (6 to 16) in the control group. No antibiotic class was seen more often in the CDI group. Macrolides, mostly azithromycin, were seen more often in the control group (OR 0.30 (0.09 to 0.82), P = 0.016).

Conclusion
We did not see a difference in the rate of ASIs in patients who tested PCR positive or negative for CDI. The rate of ASI was lower than we anticipated, reducing the chance for ASI to show an effect. Most ASIs were followed when directions were given (87.2%), leaving too few not followed (17) to meaningfully assess differences. Diarrhea and CDI often occurred before the ASI was completed, reducing the opportunity for impact. To influence this outcome, ASI need to be implemented early in the antibiotic course to see an impact.

Disclosures
Mark A. Shelly, M.D., Rebiotrix: Advisor/Consultant