bluuebunny/crossref_metadata_2025_split huggingface dataset:
97. The Utilization of Echocardiography in Children with Staphylococcus aureus Bacteremia
Authors: Bui Richard , Vallejo Jesus G , Kaplan Sheldon L , McNeil Jonathon C 
Published: November 2023

Abstract

Background
Among children with Staphylococcus aureus bacteremia (SAB) the most common focus of infection is musculoskeletal with infective endocarditis (IE) being relatively rare. Echocardiography (“echo”) is routinely performed in adults with SAB with rates of IE as high as 25%. We evaluated the utility of echo in the setting of SAB in children at a tertiary children’s hospital.

Methods
Children (&lt; 18 years-old) with at least one blood culture positive for S. aureus from 2019-2021 were identified from an ongoing surveillance study at Texas Children’s Hospital in Houston, TX. Medical records were reviewed for all subjects. For this study, we aimed to define the frequency and clinical correlates of a) the utilization of echo and b) evidence of echo-positive IE. Echo evidence of IE was based on the Duke criteria.

Results
331 cases of SAB were identified in children with a median age of 4.9 years. Medical comorbidities were present in 58% of subjects. Musculoskeletal infections were the most common diagnoses followed by CLABSI (Figure 1). 22.1% of infections were due to MRSA. The median duration of bacteremia was 1 day (IQR: 1-2). Echo was performed in 140 (42.3%) subjects. Those who underwent echo had a higher degree of medical complexity, particularly congenital heart disease (CHD, Figure 2), and had a longer duration of bacteremia (median 2 vs. 1 day, p=0.01). Four subjects underwent transesophageal echo. Nine subjects met Duke echo major criteria for IE (6.4%, Figure 3). Subjects with echo-positive IE were more likely to have CHD than those without (66.7% vs. 20.6%, p=0.006); duration of bacteremia or fever among those with and without echo positive IE were not significantly different. Among subjects with CHD and SAB, 15.6% had echo diagnosed IE. 4/9 subjects with vegetations had a single day of SAB.
Figure 2A. Depicts select clinical characteristics with respect to their frequency among subjects who did or did not undergo echocardiogram. Figure 2B. Demonstrates the relative proportion of cases with community-associated, community-onset healthcare-associated and hospital-associated infection.
The figure illustrates select clinical characteristics for subjects with echocardiogram confirmed infective endocarditis (IE)

Conclusion
While a large proportion of children with SAB at our center underwent echo, the frequency of IE by imaging was approximately 6%. Children with CHD are at high risk for IE, however, identifying other children who would benefit the most from echo in the setting of SAB is challenging. Notably, even with short durations of SAB, IE was documented in children with comorbidities. Further multicenter work with very large sample sizes is needed to optimize echo use in children with SAB.

Disclosures
Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support
99. Predictive model for serious bacterial infections in infants less than 90 days of age based on clinical data and a combination of high-threshold inflammatory biomarkers
Authors: Dabaja-Younis Halima , Makhoul Nadeen , Abu Shqara Rozeen , Damouni Shalabi Ranaa , Reiner-Benaim Anat , Green Green Manfred S , Kassis Imad 
Published: November 2023

Abstract

Background
Serious bacterial infection (SBI) is a life-threatening condition affecting infants less than 90 days of age, and prompt differentiation from non-bacterial infection (NBI) is crucial. Recent guidelines recommend a combination of low-threshold inflammatory biomarkers that need further validation. The aim of this study is to develop predictive models for SBI in infants &lt; 29 days and in infants aged 29-90 days. The study uses detailed clinical data and inflammatory biomarkers with high thresholds.

Methods
This retrospective cohort study was conducted between 2010 and 2019 in a tertiary referral hospital in northern Israel. The study included previously healthy and term infants &lt; 90 days of age who were admitted to the pediatric units of the hospital with febrile illnesses. SBI was defined as bacteremia, meningitis, or urinary tract infection, while NBI was defined as absence of signs of bacterial infection. Detailed clinical and laboratory data were collected for each of the two age groups.
Chart flow of infants included in the study
a Serious bacterial infection, b Non-bacterial infection, c Urinary tract infection, d Respiratory viruses including Respiratory Syncytial Virus, Adenovirus, Influenza A, Influenza B, Parainfluenza, Human Metapneumovirus. Abbreviations: EBV Epstein bar virus, CMV- Cytomegalovirus

Results
A total of 1250 infants met the inclusion criteria, of whom 515 (41.2%) were &lt; 29 days old and 735 (58.8%) were between 29 and 89 days old. In the younger group, 95 (18.4%) had SBI. Risk factors for SBI were diarrhea, absolute neutrophil count (ANC) &gt; 7,500mm3 and CRP &gt; 3mg/dL. Viral symptoms in family members proved to be protective. In the older group, 111 (15.1%) had SBI. Risk factors for SBI were ANC &gt; 7,500mm3 and CRP &gt; 3mg/dL, while male sex, viral symptoms in family members and diarrhea were protective. The study developed a predictive model, the "NeoSBIscore", based on the above predictors, focal infection on physical examination or abnormal urinalysis. The model showed a sensitivity of 94.7% and a negative predictive value (NPV) of 96.9% in infants younger than 29 days and a sensitivity of 93.7% and a NPV of 96.2% in the older group. Only cases with urinary tract infections or bacteriuria were missed in both age groups.
"NeoSBIscore" model to identify infants admitted with febrile illness and at increased risk for serious bacterial infection.

Conclusion
The "NeoSBIscore" model successfully identified infants with SBI, and the use of higher-threshold inflammatory biomarkers did not result in missed cases of SBI, with the exception of a few cases with UTI or bacteriuria. However, external validation is required before this model can be used in clinical practice.

Disclosures
All Authors: No reported disclosures
976. Population Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analysis of Intravenous Fosfomycin for Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections
Authors: Wangchinda Walaiporn , Pogue jason M , Thamlikitkul Visanu , Leelawattanachai Pannee , Koomanachai Pornpan , (Amit) Pai Manjunath 
Published: November 2023

Abstract

Background
Intravenous (IV) fosfomycin is increasingly used globally for treatment of infections due to multidrug-resistant Gram-negative bacteria (GNB). This study aimed to determine the optimal dosage of IV fosfomycin for patients with varying degrees of kidney function.

Methods
Eligible patients were adults ≥ 18 years who were treated with IV fosfomycin 2-4 g every 6-8 hours. Five serial blood samples were collected after the 4th dose of fosfomycin and concentrations were measured and modeled by population PK analysis. Monte Carlo simulations were conducted to evaluate the probability of target attainment (PTA) of different dosages using species-specific 1-log10 kill targets (AUC24h/MIC of 98.9, 21.5, and 28.2 for E. coli, K. pneumoniae, and P. aeruginosa, respectively). The kidney function adjusted dosing regimens for E. coli are proposed by using the lowest dose that can achieve ≥ 90% PTA at an MIC of 32 (EUCAST breakpoint) and 64 µg/mL. The highest MIC values at which selected doses provide ≥ 90% PTA for K. pneumoniae and P. aeruginosa were also analyzed.

Results
A total of 138 plasma samples from 28 patients were included. The model was best described by a 1-compartment model with linear elimination. Significant covariates in final model were creatinine clearance and male sex on clearance (CL), and body weight on volume of distribution (V). The parameter estimates were CL of 0.65 ± 0.1 L/h, and V of 12.59 ± 0.8 L. The PTA of simulated dosages for E. coli are shown in Figure 1. For MIC ≤ 32 mcg/mL, a dosage of 12 g/day achieved ≥ 90% PTA for CLCR 90-120 ml/min. For MIC ≤ 64 µg/mL, a dosage of 24 g/day was needed. The proposed kidney function adjusted dosing regimens for E. coli are shown in Table 1. The highest MIC values of K. pneumoniae and P. aeruginosa where these doses provide ≥ 90% PTA were 128 and 256 µg/mL, respectively.

Conclusion
A dosage of 12 g/day of fosfomycin is required for E. coli at EUCAST susceptible breakpoint in patients with normal renal clearance and dose adjustments are needed for patients with renal insufficiency.

Disclosures
jason M. Pogue, PharmD, AbbVie: Advisor/Consultant|Entasis: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Qpex: Advisor/Consultant|Shionogi: Advisor/Consultant
1031. Can We Safely Reduce Unnecessary Blood Cultures in Patients with Suspected Infection in the Emergency Department? The PredictED Study to Develop and Validate a Bacteremia Prediction Model
Authors: Kaal Anna , Meziyerh Soufian , Dane Martijn , Kolfschoten Nikki , Steyerberg Ewout W , van Nieuwkoop Cees 
Published: November 2023

Abstract

Background
Blood cultures are commonly used at emergency departments (EDs), while only 5-10% yields a relevant pathogen. We aimed to develop an automatable prediction model in ED patients with suspected bacteremia. This may reduce the use of blood cultures and prevent potential harm from false-positive blood cultures, while minimizing the risk of missing positive cultures.

Methods
In this observational study, we included consecutive adult patients who had a blood culture taken at the ED of the Haga Teaching Hospital, the Netherlands, for a one-year period. Demographics, laboratory, and outcome data were collected from electronic patient records. We defined 23 candidate predictors for our “full model”, of which nine were used for the "basic" model because they are readily automatable (Table 1). Regression analysis with the Least Absolute Shrinkage and Selection Operator was used to define the model. Bootstrapping was performed for internal validation, including imputation of missing values. We assessed discriminative performance using the C-statistic and calibration using the calibration intercept and slope. Clinical utility was assessed by sensitivity, specificity, negative and positive predictive values and decision curves.

Results
We included 2111 unique patients; mean age 63 years and 46% male. 272 patients had true positive blood cultures (13%); 79 patients (3.7%) had contaminated blood cultures. Our basic model included 8 predictors: age, systolic blood pressure, heart rate, breathing frequency, temperature, Glasgow coma score, C-reactive protein, procalcitonin. The corrected C-statistic was 0.81 (95% CI 0.79-0.83). The full model additionally included recent antibiotic use, indwelling vascular catheter, chills, and suspected infection site. The corrected C-statistic was 0.87 (95% CI 0.85-0.88). Calibration was good for both models. Sensitivity for bacteremia was 97.4% in the basic model, saving 18% of blood cultures (Table 2). The full model could save 26% of blood cultures while maintaining a sensitivity of 98.5% (Table 3).Figure 1.Decision curve analysis

Conclusion
The proposed bacteremia prediction models are designed for easy implementation in electronic patient records and can reduce unnecessary blood cultures. Further external validation is needed before implementation in clinical practice.

Disclosures
All Authors: No reported disclosures
1036. Reporting of SARS-CoV-2 testing results among PEPFAR and non-PEPFAR countries in Sub-Saharan Africa during the first year of the COVID-19 pandemic
Authors: Johnson Benjamin C , Holmes Charles B 
Published: November 2023

Abstract

Background
The U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) is the largest global health program dedicated to addressing a single disease. In its first ten years, PEPFAR invested one-fifth of country budgets on governance and health systems strengthening, including laboratories, surveillance networks, and long-term training of health care workers. In addition to furthering the HIV response and promoting the sustainability of health programs, it has been argued these investments built capacity to respond to novel public health threats such as SARS-CoV-2.

Methods
Testing data from 1/1/2020 through 2/17/2021 were downloaded from Our World in Data, an online database that collates information from national and international health agencies. These data were cross-referenced against publicly reported testing totals from Africa CDC and the World Health Organization. The data set did not include testing reported by governments through non-machine-readable formats such as social media or press releases. PEPFAR data were drawn from PEPFAR.gov.

Results
Of the 18 countries in sub-Saharan Africa (SSA) that reported testing data one year into the pandemic, 16 (88.9%) were PEPFAR countries (Table 1). Among PEPFAR countries in SSA, 16 of 27 countries (59.3%) reported SARS-CoV-2 tests performed, compared with 2 of 21 non-PEPFAR countries (9.5%, OR = 13.8). Among countries that reported testing, PEPFAR countries had a per-capita testing rate nearly 3 times that of non-PEPFAR countries (28.7 tests per 1,000 people vs. 9.6 tests per 1,000 people), suggesting greater testing capacity. PEPFAR countries reported higher COVID-19 case rates, likely due to increased testing, however this could also be due to regional differences in incidence (Table 2). Mean GDP per capita was 62% higher in non-PEPFAR SSA countries, making it unlikely that financial resources alone account for the observed differences.Figure 1.Countries that have received PEPFAR funding and countries that reported SARS-CoV-2 testing totals during the first year of the coronavirus pandemicTable 1.Reporting of SARS-CoV-2 testing in sub-Saharan Africa among PEPFAR and non-PEPFAR countries 1 year into the COVID-19 pandemicTable 2.COVID-19 indicators and characteristics of PEPFAR and non-PEPFAR countries in sub-Saharan Africa

Conclusion
PEPFAR countries in SSA were more likely than non-PEPFAR countries to report SARS-CoV-2 testing during the first year of the COVID-19 pandemic and also reported higher per-capita testing rates. This further supports anecdotal evidence that PEPFAR’s historical investments in health systems strengthened local capacity to respond to non-HIV public health emergencies such as COVID-19.

Disclosures
All Authors: No reported disclosures
1105. Clinical outcomes in non-pregnant adults aged ≥18 years hospitalized with laboratory-confirmed RSV infection, 12 U.S. states, October 2014–April 2022
Authors: Melgar Michael , Whitaker Michael , Daily Kirley Pam , Alden Nisha B , Kim Daewi , Openo Kyle P , Brooks Alicia , Leegwater Lauren , Bye Erica , Pacheco Francesca , Barney Grant , Popham Kevin , Sutton Melissa , Talbot H Keipp , Chatelain Ryan , Havers Fiona P 
Published: November 2023

Abstract

Background
Respiratory syncytial virus (RSV) is an important cause of respiratory illness and hospitalization in older adults and adults with certain underlying medical conditions. With novel RSV vaccines in development, it is critical to identify adults at increased risk of severe illness.

Methods
Population-based surveillance was conducted through the RSV Hospitalization Surveillance Network (RSV-NET) over 8 seasons (2014–2022) across 75 counties in 12 states. We included non-pregnant adults (≥ 18 years) residing in the RSV-NET catchment area who were hospitalized with laboratory-confirmed RSV infection (clinician-directed testing) during each season (October–April, except 2020–2021, which spanned October 2020–September 2021). Demographic and outcomes data (all seasons) and underlying medical conditions (October 2014–April 2018) were abstracted from medical records. We calculated percentages of adults with intensive care unit (ICU) admission, mechanical ventilation (MV), and in-hospital death, stratified by demographic characteristics. We calculated age-adjusted percentages with these outcomes, stratified by underlying conditions.

Results
We identified 13,080 RSV-associated hospitalizations among adults; 61.9% were aged ≥ 65 years (Table 1). ICU admission was recorded in 18.6%, MV in 7.2%, and in-hospital death in 4.2%. Most in-hospital deaths (54.1%) occurred among adults aged ≥ 75 years. Among adults 18–49 years, immune compromise (34.8%) and asthma (29.8%) were the most frequent underlying conditions (Figure). Adults with non-asthma chronic lung disease (CLD) and with cardiovascular diseases had the highest age-adjusted percentages of in-hospital death (Table 2). Adults with non-asthma CLD had the highest age-adjusted percentages of ICU admission and MV.

Conclusion
Among adults with RSV-associated hospitalization, older age and cardiopulmonary conditions were associated with severe illness. Hospitalized young adults more likely had immune compromise or asthma. This study was limited by clinician-driven testing, which likely under-detected RSV-associated hospitalizations. Older adults and adults with cardiopulmonary and immune compromising conditions may benefit from RSV vaccination when licensed products become available.

Disclosures
All Authors: No reported disclosures
1168. Cost-effectiveness of high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccine for older people in a country with high influenza vaccination rate
Authors: Nham Eliel , Seong Hye , Hyun Hakjun , Yoon Jin Gu , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Kim Eugene , Choi Leejung , Lee Jung-Min , Song Joon Young 
Published: November 2023

Abstract

Background
The high-dose quadrivalent formulation (QIV-HD) has shown improved protection against influenza and its complications in older adults. We aimed to evaluate the cost-effectiveness of QIV-HD compared with QIV-SD among Korean adults aged ≥ 65 years in reducing influenza-related disease burden.

Methods
We evaluated the 2016/2017 and 2017/2018 seasons and their average values using a static decision tree model. For the main analysis, hospitalization was defined as cardiorespiratory disease-related. The difference in efficacy between standard-dose (SD) and high-dose (HD) was calculated based on the results of a clinical trial comparing Fluzone® High-Dose Vaccine and Fluzone® Vaccine in older adults. Incremental cost-effectiveness ratios (ICERs) were assessed from the healthcare system perspective. A discount rate of 4.5% was applied to life-year-gained (LYG) values and utilities. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economic sources of uncertainty.

Results
In the analysis of the 2017/2018 season, the QIV-HD strategy generated an excess of 0.003953 quality-adjusted life-years (QALYs) compared with QIV-SD. The ICER was 6,467.56 USD/QALY. For the 2016/2017 season, QIV-HD caused an excess of 0.003272 QALYs and ICER was 7,902.46 USD /QALY. From the average data of the two seasons, an excess of 0.003561 QALYs were generated and the ICER was 7,190.44 USD/QALY. In the one-way sensitivity analysis, the parameters with the greatest impact on the results were the relative VE of QIV-HD vs. QIV-SD against influenza-associated hospitalization. PSAs were conducted for the 2016/2017 and 2017/2018 seasons, with the cost of the QIV-HD vaccine fixed at 50,000 KRW (40.48 USD) or 65,000 KRW (52.62 USD). The results showed that for a WTP threshold of 24,692.36 USD/QALY, the probability that QIV-HD is a cost-effective option for the Korean health system is 100% in all seasons and QIV-HD vaccine costs considered.

Conclusion
From the healthcare system perspective, QIV-HD was a more cost-effective vaccination option in reducing influenza-related disease burden and healthcare costs in Koreans aged ≥ 65 years compared with QIV-SD.

Disclosures
Hee Jin Cheong, M.D., Ph.D., Sequiris: Advisor/Consultant Jung-Min Lee, n/a, Sanofi Korea: Stocks/Bonds
1169. Unconjugated Multi-epitope Peptides Adjuvanted with ALFQ Induce Durable and Broadly Reactive Antibodies to Human and Avian Influenza Viruses
Authors: Rikhi Nimisha , Sei Clara J , Rao Mangala , Schuman Richard F , Kroscher Kellie , Matyas Gary R , Muema Kevin , Lange Camille , Assiaw-Dufu Aba , Hussin Elizabeth , Jobe Ousman , Alving Carl R , Fischer Gerald W 
Published: November 2023

Abstract

Background
Traditional influenza vaccine production often leads to mismatch due to antigenic drift, thereby reducing protection. Alternate vaccine strategies that are peptide-based, nanoparticle-based or nucleic acid-based are being developed. Composite multi-epitope peptides provide a cost-effective and easily scalable strategy towards a universal influenza vaccine. In this study, we demonstrate that unconjugated, multi-epitope peptides formulated with the highly potent adjuvant Army Liposome Formulation with QS-21 (ALFQ) generate broadly reactive durable antibodies to human and avian influenza viruses when administered intramuscularly or intradermally.

Methods
ICR mice were immunized with an unconjugated composite influenza peptide vaccine comprising HA+NA (Flu Pep11) and Matrix (M1/M2/M2e)+T-cell epitope (Flu Pep5906) formulated with ALFQ. A low-dose (1 µg) and high-dose (20 µg) of vaccine was administered intramuscularly or intradermally. Isotype-specific IgG titers to composite peptides, individual epitopes, and multiple strains of influenza A (H1N1, H3N2, H5N1), and B (Yamagata, Victoria) were analyzed by ELISA. Neutralizing titers against Group 1 and Group 2 viruses were determined using microneutralization assay.

Results
A robust IgG1 and IgG2b antibody response was seen at day 21 post primary immunization and remained steady for all groups up to day 200 (duration of study). IgG2a and IgG3 titers were also generated. Antibodies recognized multiple strains each of human and avian influenza A and influenza B virus subtypes, 200 days post primary immunization, and were comparable between doses and routes. Strong neutralizing titers were shown against Group 1 and 2 influenza viruses.

Conclusion
An unconjugated peptide vaccine comprising multiple highly conserved epitopes of HA, NA and Matrix formulated with ALFQ adjuvant and administered intramuscularly or intradermally, generated broad and durable antibodies to human and avian influenza viruses. Induced antibodies neutralized seasonal and pandemic influenza strains. These composite peptides adjuvanted with ALFQ generate durable and broad immunity and provide a cost-effective and easily scalable strategy that moves us closer to a universal influenza vaccine.

Disclosures
All Authors: No reported disclosures