bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1851. Influence of the COVID-19 Pandemic on Antimicrobial Resistance Patterns in Pediatric Group A Streptococcus Infections in Houston, TX
Authors: Segura Maria Gabriela , Aboulhosn Aya , Sanson Misu A , Vega Luis , Chinwala Sakina , Sommer Lauren M , McNeil Jonathon C , Flores Anthony R 
Published: January 2025

Abstract

Background
Group A Streptococcus (GAS) causes a large spectrum of disease, including invasive, pharyngeal and skin / soft tissue (SSTI)1. Penicillin remains the mainstay therapy but recently, resistance to second-line therapies has steadily increased, especially after COVID19, with macrolide-resistant GAS as an emerging threat2. Given recent surges of GAS associated with later stages of the pandemic,4 we sought to compare pre-pandemic (2013-2019) and pandemic (2020-2023) GAS epidemiology and antimicrobial resistance patterns.Figure 1Total number of isolates and distribution of disease types per year.

Methods
GAS isolates were collected from Texas Children’s Hospital laboratory from January 2013-December 2023 and grouped into pre-pandemic and pandemic periods. Disease type [invasive (INV), skin and soft tissue infection (SSTI), or pharyngeal (PHG)] was determined from the medical record. Isolates were grown, stocked and emm typed5. Resistance to tetracycline, erythromycin, and clindamycin was determined by disk diffusion. Intermediate and resistant strains were collectively considered non-susceptible (NS).Figure 2Frequency of antibiotic non-susceptibility by year

Results
We analyzed 2,717 isolates (pre-pandemic n=1640; pandemic n=1077) and observed a similar distribution of disease types between the two periods (Figure 1). Distribution of emm types differed with emm12 (1.7-fold) and emm3 (1.6-fold) increasing significantly and emm89 (0.6-fold), emm4 (0.6-fold), emm87 (0.4-fold) and emm6 (0.3-fold) decreasing significantly. Overall NS to any antibiotic increased from 19% to 39% between the two periods (P&lt; 0.0001). NS in the pandemic period was primarily driven by NS to clindamycin, increasing by &gt;3-fold (6% vs 20%) (Figure 2). Among emm types showing NS to clindamycin pre vs pandemic, emm28 increased 10-fold (3% vs 31%, P&lt; 0.0001), emm1 increased 5-fold (5% vs 24%, P =&lt; 0.001), and emm12 increased 2.6-fold (6% vs 16%, P&lt; 0.001) (Figure 3). NS to any antibiotic increased independent of disease type between the two periods.
Figure 3 Frequency of clindamycin non-susceptibility by emm type

Conclusion
NS increased significantly in pandemic period, mostly driven by NS to clindamycin. A small subset of emm types disproportionately contributed to clindamycin NS in pandemic period, although the mechanism remains unknown. Clinicians should be aware of the possible reduced effectiveness of clindamycin in pediatric GAS infections.

Disclosures
Jonathon C. McNeil, MD, Nabriva: site investigator on clinical trial Anthony R. Flores, MD, MPH, PhD, GlycosBio, Inc: Grant/Research Support
P-1855. Dissecting the contribution of Herpesviruses in the emergence of depressive symptoms in Alzheimer's Disease through multi-omics data
Authors: Onisiforou Anna , Zanos Panos 
Published: January 2025

Abstract

Background
The association between members of the Herpesviridae family and the development of Alzheimer's Disease (AD) and Depression is well-documented. However, the specific pathogenic mechanisms through which herpesviruses contribute to the co-occurrence of AD and major depression remain poorly elucidated.

Methods
To explore this hypothesis, we employed an integrated multi-omics bioinformatics approach combining virus-host protein-protein interactions (PPIs) and transcriptomic data. This method was utilized to dissect the complex interplay between herpesvirus infections and the host biological pathways that might be jointly involved in AD and major depression.

Results
Our findings indicate significant overlaps in the herpesvirus-modulated pathways in AD and those implicated in major depression. Notably, specific herpesviruses were found to influence pathways related to neuroinflammation, synaptic function, and mood regulation, which are critical in both AD and depression. Additionally, co-infection with multiple Herpesviridae members was associated with increased susceptibility to developing comorbid AD and major depression.

Conclusion
This study supports the hypothesis that herpesviruses contribute to the pathogenesis of both AD and major depression through shared biological pathways. These insights highlight the potential of targeting these pathways in therapeutic strategies for patients suffering from both conditions. Furthermore, our results underscore the importance of considering viral infections in the clinical management of AD and comorbid depressive symptoms.

Disclosures
All Authors: No reported disclosures
P-1868. Incidence of Rhabdomyolysis in Patients Receiving Daptomycin in a Community Hospital OPAT Program
Authors: Cid Allison N , Gibson Heather D , Arnoczy Gretchen S , Jawanda Jaspaul S , Biritwum Madonna A , Di-Majo Amanda , LeViere Anna 
Published: January 2025

Abstract

Background
Daptomycin is a favorable medication for outpatient parenteral antimicrobial therapy (OPAT) due to its low rate of serious adverse events, however one potential therapy complication is the development of rhabdomyolysis. The aim of this study was to determine the incidence of rhabdomyolysis within a community hospital’s OPAT program.

Methods
A retrospective chart review was performed of patients enrolled in the OPAT program and who received daptomycin therapy from December 2022 to August 2023. The primary outcome of the study was the percentage of patients who developed rhabdomyolysis while on daptomycin therapy. Secondary outcomes included the determination of any patient- or drug-specific risk factors that may have increased the risk of rhabdomyolysis. Patients were included if they were discharged on daptomycin and followed by the formal OPAT program during the study period. Patients who were less than 18 years of age or pregnant were excluded.

Results
There were 83 patients who received daptomycin during the study period and 5/83 (6%) developed rhabdomyolysis. There were 8 (9.6%) patients who had an elevated creatinine kinase (CK) but did not have further progression to rhabdomyolysis. The median daptomycin dose given to patients was 8 mg/kg. Four out of the five patients with rhabdomyolysis were female (80%). The mean BMI of those who developed rhabdomyolysis was 37.9. The mean onset of rhabdomyolysis was 10.8 days. No patients with rhabdomyolysis were on a concomitant statin. None of the five patients experienced death or permanent organ failure.

Conclusion
The development of rhabdomyolysis in our study was higher than anticipated based on previous phase 3 studies. This difference may be due to higher dosing used between studies. Potential factors to consider for increased risk of rhabdomyolysis based on this study include female gender and BMI greater than 35. Statin use did not appear to be associated with an increased risk of rhabdomyolysis. Daptomycin is still a safe and effective antibiotic in the OPAT setting, however CK should be closely monitored.

Disclosures
All Authors: No reported disclosures
P-1877. Daptomycin-Induced Creatine Phosphokinase Elevations Among Patients Requiring Outpatient Parenteral Antimicrobial Therapy
Authors: Berg Deanna , Binkley Amanda , Maguire Christina , Norris Anne , Athans Vasilios 
Published: January 2025

Abstract

Background
Daptomycin, a lipopeptide with broad-spectrum gram-positive activity, requires once-daily dosing with weekly creatine phosphokinase (CPK) monitoring for daptomycin-induced muscle injury. There is a paucity of data that describes the incidence of CPK elevations among patients who require extended durations of daptomycin outpatient parenteral antimicrobial therapy (OPAT). Variables associated with elevated CPK levels include high-dose daptomycin (≥ 8 mg/kg), elevated body mass index, and concomitant medication. This study sought to describe the laboratory monitoring and safety profile of daptomycin when used in the OPAT setting.

Methods
We conducted a retrospective, multicenter cohort study of adults who received daptomycin OPAT for at least seven days between January 1, 2022, and December 31, 2023. Patients with an unknown or elevated baseline CPK were excluded. CPK toxicity grades are defined as Grade 0 (≤ 200 U/L), Grade 1 (201-500 U/L), Grade 2 (501-1000 U/L), Grade 3 (≥ 1000 U/L). The primary endpoint was the incidence of CPK elevations during daptomycin OPAT. Secondary endpoints include characterizing factors associated with CPK elevations and safety outcomes.

Results
A total of 188 patients were included in the analysis. Most patients were treated for osteomyelitis (46%), endovascular (19%), or prosthetic joint infection (18%) caused by either staphylococci (63%) or enterococci (19%). The median weight-based daptomycin dose was 7 mg/kg (actual body weight) (IQR 6 – 8), and the median treatment duration was 38 days (IQR 24 – 42 ). A total of 86 patients were on concomitant statin therapy, of which 54% were on a high-intensity statin, and 79% were on a lipophilic statin. CPK toxicity Grade 0 was the highest toxicity among 70% of patients on statin therapy. There were 47 patients (25%) who experienced any CPK elevation (Grade ≥ 1), of which the majority were asymptomatic (44/47, 94%), and CPK elevation led to discontinuation of therapy in 18 patients (Table 1).

Conclusion
The majority of the patients were able to tolerate prolonged daptomycin therapy. Concomitant statin therapy was continued in most patients. Repeat CPK testing in asymptomatic patients and assessment of confounding factors may be appropriate prior to early discontinuation of daptomycin therapy.

Disclosures
Amanda Binkley, PharmD, BCIDP, AAHIVP, Viiv: Advisor/Consultant Christina Maguire, PharmD, Viiv: Advisor/Consultant
P-1930. Absence of Booster Vaccination and Low Cycle Threshold Values Predict Severe and Critical COVID-19 in Fully Vaccinated Individuals: A Multi-Center Retrospective Cohort Study
Authors: Rivera Charles Kevin L , Donna Cruz Ia Marie , Carascal Mark , Perez Ma Cristina , Destura Raul V , Henson Karl Evans R 
Published: January 2025

Abstract

Background
The development of severe/critical Coronavirus Disease 2019 (COVID-19) infection in fully vaccinated individuals is an incompletely defined area of research and lacks clinical scoring tools. Most scoring systems were assessed with unvaccinated patients, making it less clinically applicable in today’s global landscape. Our study validated an existing clinical prediction tool using data from vaccinated individuals and created a new model that could provide improved prediction accuracy.

Methods
Adults fully vaccinated against COVID-19 and admitted to two Philippine tertiary hospitals from March 2021 to August 2022 for breakthrough infections were enrolled. Clinical characteristics, type and number of vaccine doses, and rt-PCR cycle threshold (CT) values were collected. The primary outcome of interest was the development of severe/critical COVID-19. An existing severe/critical COVID-19 prediction tool was validated using the study data, while a new and simpler scoring system was developed from the multiple logistic regression analysis of significant variables.Table 2:Final Model with Significant Factors

Results
Among 803 adults with COVID-19, 138 (17%) received at least one booster dose, and 139 (17%) progressed to severe/critical disease. The existing prediction tool had a sensitivity (Sn) of 96.5%, specificity (Sp) of 11.7%, and area under the receiver-operator curve (AUROC) of 0.54. Multivariable logistic regression showed that age &gt;75y (OR 2.86; 95% CI 1.56 - 5.21), diabetes mellitus (OR 1.76, 95% CI 1.10-2.80), CT value &lt; 20 (OR 1.90; 95% CI: 1.19 - 3.03), suspicion of bacterial co-infection (OR 2.85, 95% CI 1.60-5.07), and non-receipt of a booster dose (OR 0.32; 95% CI: 0.15 - 0.72) were independent risk factors for developing severe/critical COVID-19. The developed scoring system showed a Sn of 89.4%, Sp of 62.7%, and AUROC of 0.76.

Conclusion
A simplified scoring tool using five variables may help predict the progression to severe/critical COVID-19 in fully vaccinated individuals. Although the tool has modest Sn and Sp, it can help triage patients and guide initial therapy. Validation of this tool in larger studies is recommended.

Disclosures
Karl Evans R. Henson, MD, FIDSA, BSV Biosciences: Honoraria|Cathay Drug Company, Inc: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria
P-1937. Multisystem inflammatory syndrome in children (MIS-C) - Accurate Diagnosis for Targeted Treatment
Authors: Sundararajan Sanjana , Pinninti Swetha , Boppana Suresh 
Published: January 2025

Abstract

Background
Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory post-acute COVID-19 condition that clinically overlaps with Kawasaki disease (KD). However, the recommended first-line therapy differs for these two conditions. The Centers for Disease Control (CDC) and centers for state and territorial epidemiologists (CSTE) updated the surveillance case definition for MIS-C in 2023 to improve specificity. Since it has been suggested that 15%-20% of children identified using the 2020 definition will not meet the updated definition. While the incidence of MIS-C has decreased, waning immunity and low vaccine uptake in children requires continued vigilance and research. The objective of this study is to determine the utility of the 2023 CSTE/CDC definition to identify children with MIS-C at a quaternary care pediatric center.

Methods
Children diagnosed and treated for MIS-C at the Children’s of Alabama (COA) between January 2020 and December 2022 were enrolled in a prospective follow-up study. Demographic, clinical, and laboratory data, and treatment regimens were abstracted from the electronic medical record (EMR). The CDC 2020 and the 2023 CTSE/CDC criteria were applied to the cohort.

Results
The study cohort includes 126 children diagnosed and treated for MIS-C at COA between 2020 and 2022. The demographic and clinical features are summarized in Table 1. Of the 126 children, 92.8% (117/126) and 93.6% (118/126) respectively met the 2020 and the updated 2023 definition for MIS-C. While 81.7% (103/126) of children were treated with IVIG + steroids, 18% (23/126) were treated with IVIG only. In addition, 12 children required immunomodulators (Anakinra /Remicade /Infliximab) for resolution of symptoms after treatment with IVIG + steroids. Favorable short and mid-term outcomes were documented in all children in this cohort.

Conclusion
Over 90% of children with MIS-C met the criteria for MIS-C diagnosis with either the 2020 or the revised 2023 definition. The lack of definitive clinical or laboratory biomarkers and significant clinical overlap with other entities makes it challenging to identify all children with MIS-C highlighting the need for a better understanding of the pathogenesis, biomarker discovery, and effective therapies.

Disclosures
Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support
P-1942. Unexpected Cardiac Deaths in Patients with COVID-19 Infection
Authors: Malik Aimon , Jabeen Atika , Chemaitelly Hiam , Thomas Anil G , Shams Sherin , Saleem Samah , Bhutta Zain A , Azad Aftab M , Al Khal Abdullatif , Abu-Raddad Laith J , Abou-Samra Abdul-Badi , Butt Adeel A 
Published: January 2025

Abstract

Background
There are contradictory reports regarding the association of COVID-19 with sudden cardiac deaths. It is unclear whether these deaths are the result of known cardiac disease and risk factors or are unexpected based on prevalent risk factors. Our aim was to determine the association between COVID-19 infection and UCD among individuals who died of a cardiac cause in Qatar.
Study Flowsheet

Methods
All deaths in Qatar in adults &gt;18 years old with any cardiac cause listed as the primary or immediate cause of death were individually reviewed to determine whether the death was unexpected based on the individual’s clinical risk profile. For each case of validated UCD, up to 5 controls with a non-cardiac primary cause of death were identified, matched on age groups, sex, nationality, number of coexisting conditions, and vaccine doses to individuals who died of non-cardiac causes in the same calendar month. Adjusted odds ratios (aOR) comparing odds of prior COVID-19 infection in cases relative to controls were estimated using conditional logistic regression.
Association between prior COVID-19 infection and incidence of Unexpected Cardiac Deaths (UCD) in the matched cohorts.

Results
Among a total of 10,541 deaths, we matched 326 UCD cases to 604 controls with a non-cardiac cause of death. The median age was 48 years for cases and 49 years for controls, 87% were male, and 18% of cases and 20% of controls were Qatari nationals. Approximately three-quarters in each group had no documented comorbidities, and approximately two-thirds were unvaccinated. Prior COVID-19 infection was not associated with a higher risk of UCD (aOR 0.74, 95% CI 0.48, 1.13). No association was observed between prior COVID-19 and UCD in subgroup analyses by age groups, or vaccination status. Qatari nationals, females, and those with &gt; 4 comorbidities were less likely to experience UCD associated with prior COVID-19.

Conclusion
COVID-19 is not associated with an increased risk of UCD. The observed cardiac deaths are more likely due to the underlying risk profile of the decedents.

Disclosures
Adeel A. Butt, MD, MS, Gilead Sciences: Grant/Research Support
P-1946. Epidemiology and Factors Associated with SARS-CoV-2 Transmission Among Students Following Resumption of Face-to-Face Classes in a Private University in Metro Manila, Philippines
Authors: Do Dianne Hazel P , Padua Jay Ron O 
Published: January 2025

Abstract

Background
Coronavirus disease (COVID-19) has brought disruptions in our lives including the education system. In the Philippines, the education system has transitioned to online and modular distance learning delivery of instruction due to the pandemic. To date, there has been no local study on the clustering rates within schools in the Philippines following resumption of face-to-face classes. This study aims to describe the demographic and clinical characteristics of students with confirmed COVID-19 and to determine the incidence of clustering among students after resumption of face-to-face classes.

Methods
A retrospective cross-sectional study on high school and college students of a private university with confirmed COVID-19 during the Academic Years (A.Y.) 2021-2022 and 2022-2023. Data was collected through digital medical charts review and analysis done using real statistics, multiple logistic regression model and cluster analysis.

Results
More female students were affected than male students in the senior high school and college level while almost equal distribution was seen among the junior high school level. Majority were fully vaccinated to COVID-19 with 1 booster dose. The presumed route of transmission was mostly from close contacts in school. Most common symptoms were cough, colds and fever. Most infections were mild. Among those vaccinated, the timing of infection from last vaccination showed varied results (9 to less than 12 months in junior high; 3 to less than 6 months and 6 to less than 9 months in senior high and college). The timing of recovery did not show significant difference (p-value=0.637) among different education levels. Based on the regression analysis, there is no variable which can be significantly associated with transmission of infection among close contacts either at school or at home. The highest number of cases and clustering were observed among medical and health-allied colleges and programs.

Conclusion
Based on the study results, clustering can occur in school settings in the Philippines. Despite the low cases in the community, transmission is still present among university students. Therefore, infection prevention and control strategies must still be strictly observed until the virus is completely eradicated in order to prevent sporadic outbreaks.

Disclosures
All Authors: No reported disclosures
P-1949. The Self-Controlled Risk Interval: An Evolving Method for Vaccine Effectiveness Estimation in Complex Real-World Data
Authors: Fix Jonathan , Marchese Anthony M , Beyhaghi Hadi , Rousculp Matthew D 
Published: January 2025

Abstract

Background
Post-marketing assessments of vaccine effectiveness (VE) are critical to informing health policy, understanding real-world vaccine performance, and ensuring confidence in vaccination efforts, though imperfect comparator groups can limit the accuracy of VE assessments. The self-controlled risk interval (SCRI) design, a case-only analytic method historically used in safety studies, controls for time-invariant confounding using within-person comparisons and has recently been used to assess VE. This targeted review identifies and characterizes SCRI’s growing role in VE research.Table 1:Vaccine Effectiveness Studies that Used the Self-Controlled Risk Interval Design

Methods
Targeted database searches were conducted in Medline, Embase®, Embase Preprints, and BIOSIS Previews®, and the preprint servers: medRxiv, preprints with The Lancet, and Research Square. Key terms (and related variations) included: vaccine effectiveness, COVID-19 vaccines, and self-controlled risk interval.

Results
Two VE studies that used the SCRI design were identified (Table 1). Both were retrospective database studies (one using electronic health records and the other insurance claims data), evaluated SARS-CoV-2 infection, and used similar post-vaccination control windows, but featured different post-vaccination risk windows and were conducted among notably different populations. An additional 10 identified studies included post-vaccination person-time in the comparison group but did not make within-person comparisons to address important potential confounding, acknowledging that post-vaccination benefits are not appreciated immediately. These studies varied in the study populations, outcomes assessed, comparison group composition, and analytic methods.

Conclusion
Use of SCRI for VE estimation has been limited; however, the increasing inclusion of post-vaccination control arm person-time in other COVID-19 VE studies merits the broadening of its application. The results of this review suggest that, in the context of COVID-19, SCRI VE evaluation is a promising tool where there are no suitable comparison groups, increasingly complex individual backgrounds (e.g., infection history, number and timing of doses, or heterologous vaccination), or insufficient information for confounding control.

Disclosures
Jonathan Fix, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Hadi Beyhaghi, MD, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Matthew D. Rousculp, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)