bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring XNA polymerase fidelity in a hydrogel particle format
Authors: Medina Esau L , Chaput John C 
Published: January 2025

Abstract
Growth in the development of engineered polymerases for synthetic biology has led to renewed interest in assays that can measure the fidelity of polymerases that are capable of synthesizing artificial genetic polymers (XNAs). Conventional approaches require purifying the XNA intermediate of a replication cycle (DNA → XNA → DNA) by denaturing polyacrylamide gel electrophoresis, which is a slow, costly, and inefficient process that requires a large-scale transcription reaction and careful extraction of the XNA strand from the gel slice. In an effort to streamline the assay, we developed a purification-free approach in which the XNA transcription and reverse transcription steps occur inside the matrix of a hydrogel-coated magnetic particle. Accordingly, a DNA primer cross-linked throughout the gel matrix is annealed to a template of defined sequence and extended with XNA. Following removal of the DNA template, the XNA product strand is copied back into DNA, recovered, amplified, cloned, and sequenced. Performing the replication cycle in the hydrogel format drastically reduces the time and reaction scales required to measure the fidelity of an XNA polymerase, making it easier to evaluate the properties of a range of candidate XNA polymerases.
Multifaceted roles of H2B mono-ubiquitylation in D-loop metabolism during homologous recombination repair
Authors: Hung Shih-Hsun , Liang Yuan , Heyer Wolf-Dietrich 
Published: January 2025

Abstract
Repairing DNA double-strand breaks is crucial for maintaining genome integrity, which occurs primarily through homologous recombination (HR) in Saccharomyces cerevisiae. Nucleosomes, composed of DNA wrapped around a histone octamer, present a natural barrier to end resection to initiate HR, but the impact on the downstream HR steps of homology search, DNA strand invasion, and repair synthesis remain to be determined. Displacement loops (D-loops) play a pivotal role in HR, yet the influence of chromatin dynamics on D-loop metabolism remains unclear. Using the physical D-loop capture and D-loop extension (DLE) assays to track HR intermediates, we employed genetic analysis to reveal that H2B mono-ubiquitylation (H2Bubi) affects multiple steps during HR repair. We infer that H2Bubi modulates chromatin structure, not only promoting histone degradation for nascent D-loop formation but also stabilizing extended D-loops through nucleosome assembly. Furthermore, H2Bubi regulates DNA resection via Rad9 recruitment to suppress a feedback control mechanism that dampens D-loop formation and DLE at hyper-resected ends. Through physical and genetic assays to determine repair outcomes, we demonstrate that H2Bubi plays a crucial role in preventing break-induced replication and thus promoting genomic stability.
102. Carbapenemase producing organisms in Positive Blood and urine Cultures in a large New York Health System Reveals Emergence of NDM-Harboring Organisms and Associated Morbidity and Mortality
Authors: Haghamad Aya , Shou Ryan , An Kirby , Lemon Jamie , Juretschko Stefan , Streva Vincent 
Published: January 2025

Abstract

Background
Infections caused by organisms harboring carbapenemase genes are a significant cause of morbidity and mortality. The prevalence of carbapenemase producing organisms (CPO) has been increasing for several years, with the majority of isolates originating in healthcare settings and containing one of the five most prevalent carbapenemase genes (blaKPC, blaOXA-48-like, blaNDM, blaVIM, blaIMP). Management of patients with CPOs is particularly challenging and knowledge of the specific carbapenemase gene harbored by these organisms is imperative for proper treatment.

Methods
We conducted a retrospective multicenter study of hospitalized patients with blood and urine cultures positive for a CPO from January 2021 to December 2023 (2021-2023 blood, 2023 for urine). Blood culture PCR results were utilized to identify carbapenemase genes from these specimens. For urine specimens, phenotypic carbapenemase production was assessed by a lateral flow immunoassay (NG-Test CARBA 5). Clinical outcomes including time to appropriate therapy, length of hospital stay, 30-day hospital readmission, and patient mortality were evaluated.

Results
A total of 71 CPO-positive blood cultures and 50 CPO-positive urine cultures from 10 hospitals were included. Klebsiella pneumoniae was the predominant CPO isolated from both blood and urine samples, urinary tract infections was the most common source of CPO bacteremia. Of the carbapenemase resistance genes detected, blaNDM comprised 39% of CPO isolated from blood and 46% of CPO isolated from urine. Median time to appropriate therapy was 3.9 hours for blood cultures and 16 hours for urine cultures. The median length of hospital stay was 20 days for blood infections and 13 days for urine infections. Thirty-day readmission rates were 16% for blood infections and 50% for urine infections, with mortality rates of 39% for blood infections and 6% for urine infections.

Conclusion
Timely identification and differentiation of carbapenem resistance genes are crucial for informing adjustments in antimicrobial therapy. Despite appropriate clinical interventions patients with CPO bacteremia had elevated mortality rates, 42% in 2022 and 33% in 2023. Notably, the primary contributor to these high mortality rates was NDM, with rates reaching 54% in 2022 and 50% in 2023.

Disclosures
All Authors: No reported disclosures
171. Retrospective Review of Management of Acute Otitis Media in a Canadian Pediatric Emergency Department
Authors: Mhapankar Gunjan , Krueger Carsten , Alqurashi Waleed , Sucha Ewa , Webster Richard , Bowes Jennifer , Le Saux Nicole 
Published: January 2025

Abstract

Background
Acute Otitis Media (AOM) is a leading cause of antibiotic prescription in children. Watchful waiting is the preferred strategy for AOM management for mildly ill children ≥ 2-years-old however current clinical practice varies. This study aims to compare published AOM guidelines by the Canadian Pediatric Society (CPS) with clinical practice in a Canadian academic tertiary care emergency department (ED).

Methods
We performed a retrospective review on AOM ED visits at the Children’s Hospital of Eastern Ontario (CHEO) from 1/2021 to 12/2021. Measures of non-adherence to the CPS AOM guideline were defined as follows: missed opportunity for watchful waiting, diagnostic criteria absent or not recorded, prolonged duration of treatment, lack of immediate treatment, and inappropriate agent. Additionally we explored if guideline-discordant antibiotic prescribing practices differ by geographic locale (rural vs non-rural as determined by postal code) and preferred language. The postal code was linked to a Material and Social Deprivation Index (MSDI) from INSPQ as a proxy for socio-economic status.

Results
442 patients were included (Table 1). 66.5% patients met criteria of non-adherence (Table 2). 41.9% patients received antibiotics despite being categorized as mildly ill. 29.6% patients received antibiotics, despite having no/undocumented middle ear effusion or bulging tympanic membrane. 6.6% received longer duration of antibiotics (10 days) despite lack of complications such as perforation. 4.1% received non-penicillin antibiotics as first-line treatment. 1.4% received parachute prescriptions despite being categorized as severely ill. After controlling for language and rurality, the odds of being in any non-adherence group were not higher for patients in higher deprivation quintiles compared to those in the lowest deprivation quintile (Figure 1, 2).Figure 1.Distribution of Material Deprivation Quintiles by Non-adherence Type

Conclusion
2/3rd of ED patients met criteria of guideline non-adherence. Material deprivation was not a predictor of non-adherence. The two domains of watchful waiting and applying diagnostic criteria can serve as specific benchmarks to improve antibiotic prescribing practices in ED settings. Pragmatic management of AOM using current guidelines may be biased towards immediate treatment rather than timely follow-up.Figure 2.Odds ratio of any non-adherence for material deprivation quintile adjusted for language and rurality

Disclosures
All Authors: No reported disclosures
208. Exposure-response relationship of ceftazidime/avibactam in adults with central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae: a prospective observational study
Authors: Li Nanyang , Yang Lei , Zhu Xu , Li Wanzhen , Ye Xiangru , Gao Liang , Li Lei , Wu Jufang , Zhang Jing , Hu Jin , Mao Ying 
Published: January 2025

Abstract

Background
Central nervous system (CNS) infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant challenges for clinicians in ICU. Achieving optimal drug exposure in the cerebrospinal fluid (CSF) is crucial for good outcomes. This study aimed to evaluate the exposure-response relationship of ceftazidime/avibactam (CZA) in plasma and CSF.

Methods
All patients received CZA (2.5 g), IV infusion (over 2 hours), q8h. At steady-state after the fourth dose of CZA, the concentrations of CZA in the plasma and CSF were determined by ultra-performance liquid chromatography (UPLC) at 1, 2, 2.25, 2.5, 3, 4, 6, and 8 h post-dose. The PK/PD index of ceftazidime (CAZ) and avibactam(AVI) was calculated for each patient. Demographic, clinical efficacy, microbiological eradication, and 28-day mortality were reviewed. Blood and CSF samples were collected for calculation of PK parameters by non-compartmental pharmacokinetics (PK) modeling. The attainment of CAZ and AVI PK/PD targets in plasma and CSF was calculated to assess the exposure-response relationship of CZA and the corresponding clinical efficacy rate and bacterial eradication rate.

Results
CAZ and AVI demonstrated good penetration into CSF, evidenced by median CSF/plasma AUCtau ratio of 43.8 % and 55.8 %, respectively. CZA 2.5 g q8h achieved CAZ PK/PD target of 50%fT &gt;MIC in both plasma and 50%T &gt;MIC in CSF of all patients and reached AVI PK/PD target of 50%T &gt;CT=1 mg/L in CSF of 80% (16/20) of patients. The dosing regimen also achieved CAZ PK/PD target of 100% fT &gt;4MIC in plasma of 9 patients and 100% T &gt;4MIC in CSF of 14 patients. At the end of the treatment, the overall clinical and microbiological efficacy rates were 80.0% and 100%, respectively. Only one case of CZA-related adverse event (Clostridioides difficile-associated diarrhoea) was reported.

Conclusion
The good CSF penetration of CZA enables the dosing regimen of CZA 2.5 g q8h a promising treatment option for CNS infections caused by CRKP.

Disclosures
Nanyang Li, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator Jing Zhang, Doctor of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator
214. Clinical Characteristics and Outcomes of Patients Treated with Tecovirimat for Mpox Disease: A Large Cohort in New York City
Authors: Leocadio Ciarra , Garcia Elizabeth A , Lash Maura , Berardi Jonathan , Chan Justin , Chasan Rachel , Esquivel Blanca C , Foote Mary K , Glesby Marshall J , Guerra Amiyah , Harris Alexander B , Knutsen Dorothy , Mannheimer Sharon , Mazo Dana , McLean Jacob , McPherson Tristan D , Meyerowitz Eric , Mgbako Ofole , Patel Gopi , Pagán Pirallo Patricia , Radix Asa , Riska Paul F , Sayegh Mark N , Shaw Raphael , Zingman Barry S , Zomorodi Rustin A , Zucker Jason , Wong Marcia 
Published: January 2025

Abstract

Background
Clinical characteristics and outcomes in patients with mpox treated with tecovirimat are not well described.

Methods
We requested retrospective deidentified data from healthcare systems in New York City (NYC) with &gt;50 tecovirimat prescriptions. Patients with probable or confirmed mpox initiating tecovirimat from May–December 2022 were included. We used a survey tool to extract demographic and clinical data from medical records. Patients reporting tecovirimat initiation at a different institution or with unknown HIV status were excluded. We used multivariable Poisson regression models with robust standard errors to examine factors associated with hospitalization and treatment delays.

Results
Of 751 eligible records, we excluded 41, leaving 708 patients in the analysis; median age was 36 years (IQR 31–43); 694 (98%) were assigned male at birth; 566 (80%) were cisgender men who have sex with men; 399 (56%) were living with HIV; and 232 (33%), 195 (28%), and 182 (26%) identified as Hispanic, non-Hispanic (NH) white, and NH Black, respectively. Reasons for treatment included proctitis (n=376, 53%), lesion type (confluent, location) (335, 47%), HIV (237, 33%), and bacterial superinfection (58, 8%). Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69,10%) (Table 1). Of 100 (14%) hospitalized patients, reasons for hospitalization included pain (25%), bacterial superinfection (22%), and dysphagia (13%) (Table 2). Median delay from symptom onset to treatment initiation was 8 days (IQR 6–11). NH Black patients had higher risk of initiating ≥8 days after symptom onset (adjusted relative risk [aRR]=1.4, 95%CI: 1.2–1.7) and being hospitalized (aRR=2.2, 95%CI: 1.4–3.5) compared with Hispanic patients, adjusting for HIV and insurance status (Tables 3,4).

Conclusion
We described common reasons for tecovirimat initiation and hospitalization. There were racial and ethnic disparities in hospitalization and treatment delays that may have been due to late presentation to care or provider-related delayed testing. More research and focused efforts to mitigate these disparities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox.

Disclosures
Ofole Mgbako, MD MS, Gilead: Advisor/Consultant
296. MDR Risk Index: Multidrug-Resistant Bacteria Probability Score for General Hospitals
Authors: Leite Edna M M , Camargos Esther , Aguiar Lilian , De Oliveira Wagner Luiz , Couto Bráulio R G M 
Published: January 2025

Abstract

Background
This research endeavors to shed light on the intricate relationship between hospitalization dynamics and the probability of acquiring multidrug-resistant bacteria (MDR) by introducing a predictive tool, the Multidrug-Resistant Bacteria Probability Score.Figure 1.Estimated Risk of MDR (Multidrug-Resistant Bacteria): Point Estimates and 95% Confidence Intervals.

Methods
We processed cultures in the hospital laboratory using automated systems and/or microdilution methods, adhering to the BR-cast guidelines. We utilized a logistic regression model to analyze four predictive variables for MDR: length of hospitalization until the collection of biological material (days), previous hospitalization (yes/no), duration of previous hospital stays (days), and admission to the Intensive Care Unit (ICU) (yes/no). The assessment focused on 7 outcomes: MDR (any type), resistance to Meropenem (RMER), production of Klebsiella pneumoniae carbapenemase (KPC), production of Extended Spectrum Beta-Lactamase (ESBL), resistance to Polymyxin (RPOL), Vancomycin-resistant Enterococci (VRE), and Methicillin-resistant Staphylococcus aureus (MRSA).Figure 2.Logistic Regression Models Estimating MDR Risk: Results for Each Type of MDR Bacteria.

Results
A total of 4,247 biological samples were collected from Nov/2022 to Nov/2023: Urine (46%), Blood (12%), Tissue Fragments (11%), Bronchoalveolar Lavage (6%), Perianal Swabs (6%), Tracheal Aspirates (4%), Nasal Swabs (3%), Abdominal Fluid (2%), Tips of Central or Umbilical Catheters (2%), Wound Secretions (1%), and Other (3%). Approximately one-third (35%) of the samples were identified as MDR. Unadjusted MDR risk: 9% RMER, 5% KPC, 8% ESBL, 1% RPOL, 3% VRE, and 4% MRSA (Fig. 1). From the seven outcomes modeled, it was possible to successfully predict five of them (Fig. 2), yielding good results in terms of predictive capability (Fig. 3). However, the modeling was unsuccessful for MRSA and ESBL. Figure 4 shows simulations of MDR risk.Figure 3.ROC Curves for the Five Successful Models Predicting Multidrug-Resistant Bacteria (MDR).

Conclusion
The duration of hospitalization prior to the collection of biological material emerges as a crucial metric, encapsulating the temporal dimension of patient exposure to potential sources of infection. All five predictive models can be effectively integrated into the patient’s electronic health record. This integration enables the timely prediction of multidrug-resistant (MDR) infections, facilitating the implementation of targeted preventive measures based on the assessed risk level.Figure 4.Simulation of MDR Risk Evolution Over Hospitalization Time: Curves Representing MDR Risk by Patient Type

Disclosures
All Authors: No reported disclosures
307. Respiratory Syncytial Virus (RSV) Infections Among Persons Aged 60 Years and Older, by Vaccination Status, reported via Electronic Laboratory Reporting (ELR) – Los Angeles County (LAC), California
Authors: Ransohoff Heidi , Frey Natalie A , Moir Olivia , Traub Elizabeth , Kim Andrea , Yeganeh Nava , de St. Maurice Annabelle 
Published: January 2025

Abstract

Background
On June 21, 2023 the CDC Advisory Committee on Immunization Practices recommended 2 different RSV vaccines for adults ≥ 60 years with shared clinical decision making. This study aims to compare the risk of laboratory-confirmed RSV infection in presumed vaccinated and unvaccinated adults ≥ 60 years living in LAC.

Methods
A population-based analysis was conducted using RSV vaccination data from the California Immunization Registry (CAIR), RSV positive case data reported to LAC Department of Public Health (DPH) via ELR between July 1, 2023 to March 20, 2024, and July 1, 2022 Population Estimates (provisional), prepared by Hedderson Demographic Services for Los Angeles County Internal Services Department, released March 2023. The study population included LAC residents ≥ 60 years at time of specimen collection. The data were matched on name, date of birth, and street address. Vaccinated cases were defined as persons who had CAIR record of RSV vaccination ≥ 14 days before specimen collection.

Results
The population of LAC residents ≥ 60 years is estimated at 2,076,677; 240,861 had RSV vaccinations in CAIR. 2,296 were ELR RSV cases: 58 (2.5%) were vaccinated; 2,238 (97.5%) were unvaccinated. The risk of ELR RSV infection among unvaccinated persons was 5.1 times higher than among vaccinated persons (Table 1; RR= 5.1; 95% CI 3.7:5.1, p &lt; 0.001). Most cases were older than 74.

Conclusion
The results show that unvaccinated older adults in LAC had a higher risk of ELR RSV infection than those who were vaccinated. Limitations include possible incomplete data in CAIR and ELR, making infection risk estimates imprecise. Future studies using these data sources may include hospitalization and death data to compare the incidence of serious illness in vaccinated and unvaccinated adults.

Disclosures
All Authors: No reported disclosures
P-811. Telavancin for Refractory MRSA Bacteremia: A 10-Year Retrospective Review
Authors: Gander Caroline , Singanamala Santhi , Holzworth Abriana , Rux Caleb , McManus Dayna , Davis Matthew W , Topal Jeffrey E 
Published: January 2025

Abstract

Background
Refractory methicillin-resistant Staphylococcus aureus (MRSA) bacteremia continues to represent a challenge in clinical treatment. Telavancin, a lipoglycopeptide with multiple mechanisms of action, has been proposed as a treatment option in these cases.

Methods
This was a single-center, retrospective chart review of adult inpatients with refractory MRSA bacteremia (defined as &gt; 72 hours of bacteremia following the start of daptomycin or vancomycin) who were treated with telavancin from December 2014 through March 2024. Patients who died or were discharged within 72 hours of starting telavancin or whose blood cultures cleared prior to the start of telavancin were excluded. More details can be seen in figure 1. The primary outcome was clinical success, defined as blood culture clearance on telavancin monotherapy. Secondary outcomes included length of time to blood culture clearance following telavancin initiation, recurrence of bacteremia within 30 days of clearance, and 30- and 90-day mortality from the time of telavancin initiation.

Results
Of 105 patients who received telavancin, 77 met inclusion criteria. Of the patients who received telavancin, 56 (72.7%) met the primary outcome, and cleared the refractory MRSA bacteremia with telavancin monotherapy. Patients who failed telavancin included 11 who did not clear blood cultures before death, 2 who cleared on telavancin plus an additional agent, and 8 who cleared after switching from telavancin to another salvage regimen. Minimum inhibitory concentrations (MICs) ranged from ≤0.5 to 2 for vancomycin, 0.094 to 2 for daptomycin, and 0.016 to 0.38 for telavancin. Other baseline characteristics can be seen in table 1. No significant differences in baseline characteristics were seen between groups. The median time to culture clearance among the clinical success group was 57 hours. Only 1.8% of these patients had recurrent bacteremia within 30 days of telavancin initiation. At 30 days from telavancin initiation, overall mortality was 21.4%, and at 90 days, 23.2%.

Conclusion
In patients with refractory MRSA bacteremia, telavancin may be a viable monotherapy salvage regimen, with mortality rates similar to those previously reported for all patients with MRSA bacteremia.

Disclosures
All Authors: No reported disclosures
P-837. Characteristics, Predisposing Factors And Clinical Outcomes of Patients with Probiotics Organisms Bacteremia
Authors: El Soufi Hind , Dahal Santosh , Doan Thien-Ly , Sohail Rubab , Sison Cristina , Akerman Meredith , Hirsch Bruce 
Published: January 2025

Abstract

Background
Bacteremia with probiotic organisms is rare. Patients’ characteristics and clinical outcomes are not well known. Our objective is to study the characteristics, risk factors and outcomes of patients with different probiotic organisms’ bacteremia.

Methods
This is a retrospective observational study of patients with probiotic organisms’ bacteremia, admitted to a New York Health system, between 2018 and 2021. 143 patients were divided into 2 cohorts. Cohort 1 (85.3%) had Lactobacillus spp bacteremia and Cohort 2 (14.7%) had positive blood culture with Saccharomyces spp or Bifidobacterium spp. Descriptive statistics were reported for patients’ characteristics, past medical history (PMH) and hospital related history (HRH). Chi-square or Fisher’s exact test was used for categorical variables and T-test or Wilcoxon test for continuous variables. Logistic regression was used to compare 30-day in hospital mortality and 30-day hospital readmission for a related infection. Negative binomial regression was used to compare hospital length of stay, duration of therapy targeted for probiotic bacteremia and number of days until blood culture clearance. P value &lt; 0.05 was considered statistically significant.

Results
50.3% were male, 59.1 % were white, 2.8 % were Hispanic or Latino. 7% had prior bacteremia within 6 months, 30.8% had concurrent bacteremia and 10.5% had concurrent fungemia with other than the probiotic organism. Patients with probiotic bacteremia (PB) had frequent comorbidities: 48% had hypertension, 36% had Diabetes Mellitus, 14.7% were immunosuppressed. 44% had central line during hospitalization, 42% had qSofa score &gt;2. PB was associated with prolonged length of stay (Mean in days 20.4) and 30-day in hospital mortality (34.3%). There were no statistical differences in PMH, HRH and outcomes between the Lactobacillus spp group and other group.

Conclusion
PB occurs in hospitalized patients with frequent comorbidities and advanced clinical illness. Caution is required in administration of probiotics in vulnerable patients.

Disclosures
All Authors: No reported disclosures