bluuebunny/crossref_metadata_2025_split huggingface dataset:
1645. Predicting Vancomycin Area Under the Curve by Bayesian-Guided Dosing in Pediatric Patients
Authors: Shin Donghyun , Park So Eun , Choi Soo-Han 
Published: November 2023

Abstract

Background
In revised consensus guidelines for therapeutic monitoring of vancomycin, the area under the curve (AUC)-guided monitoring, preferably with Bayesian estimation, is suggested for all pediatric age groups. Recommended AUC target in pediatrics is 400 mg·h/L (potentially up to 600 mg·h/L). However, there is limited pediatric data on validating Bayesian dose-optimizing and predicting vancomycin AUC. We aimed to evaluate the accuracy of the predicted AUC on vancomycin dosing adjustments based on Bayesian estimation.

Methods
We reviewed 25 pediatric patients’ data on vancomycin therapeutic drug monitoring (TDM), including trough concentrations (Ct) and AUC. A Bayesian dose-optimizing software program was used to calculate vancomycin AUC. A second TDM was taken after vancomycin dosing adjustments were performed based on the first TDM. The accuracy was calculated by the ratio of the second AUC to the predicted AUC by Bayesian dose optimization.

Results
The median age of patients was 14.3 years old (interquartile range [IQR], 9.2-16.8). The median vancomycin dosage was 41.7 mg/kg/day (IQR, 33.9-50.0). In the first TDM of vancomycin, the median Ct and AUC were 6.1 ug/mL (IQR, 2.8-11.0; 95% confidence interval [CI], 4.2-9.2) and 320.0 mg·h/L (IQR, 251.5-486.8; 95% CI, 284.0-357.0), respectively. Vancomycin dose increase was required in 68.0% of patients; the median dosage was 50.0 mg/kg/day (IQR, 38.8-60.0). Based on Bayesian-guided dosing adjustments, the median predicted AUC was 420.0 (95% CI, 380.0-447.0). In the second TDM, the median Ct and AUC were 8.7 ug/mL (IQR, 6.2-12.2; 95% CI, 7.5-11.0) and 428.0 mg·h/L (IQR, 369.7-514.0; 95% CI, 384.0-486.0), respectively. The accuracy was 1.033 (95% CI, 0.941-1.307).

Conclusion
The Bayesian AUC-guided dosing strategy may be optimal for individualizing vancomycin therapy in pediatric patients.

Disclosures
All Authors: No reported disclosures
1663. Clostridioides difficile testing following 18706 Pediatric Procedures: Implications for Diagnostic Stewardship
Authors: Negi Ruchita , Deshpande Abhishek , Arakoni Venkatraman , Foster Charles B 
Published: November 2023

Abstract

Background
Clostridioides difficile infection (CDI) poses a risk to surgical patients and antibiotic exposure may contribute to non-infectious diarrhea and unnecessary C diff testing (CDT). Our study evaluates the burden of CDT and CDI in children undergoing procedures with preoperative antibiotic prophylaxis.

Methods
A retrospective cohort study (Jan 2013-Feb 2022) analyzed CDT by Toxin B PCR in children (2-18 years) undergoing sedated procedures with preoperative antibiotic prophylaxis at Cleveland Clinic Children’s. Two step testing with EIA to confirm CDI began in Jun 2018. Perioperative data from an anesthesia database were joined with CPT4 codes and organized by procedure categories used for prophylactic antibiotic selection. CDT and CDI rates by PCR for postoperative days 3-30 were compared based on antibiotic choice (cefazolin as reference) and procedure type (orthopedics as reference) using rate ratios (RR) and mid-p exact test.

Results
A total of 14229 children underwent 18706 procedures. Postoperative CDT, PCR negative and PCR positive rates were 12.2, 10.3 and 1.9/1000 procedures, respectively (Table 1). Of 11 PCR positive tests followed by EIA, 8 were positive (73%). CDT rates were highest for gastrointestinal (GI; 48.4), thoracic (20.8) and neurosurgery (12.8) procedures (Figure 1). CDI rates by PCR were increased for GI procedures (5.9; P &lt; 0.001) and did not differ by antibiotic category. Compared to orthopedic procedures, the RR for negative CDT was highest for GI procedures 71.46 (28.73-229.4; P &lt; 0.001). For antibiotics (Figure 2), the lowest CDT rate was for cefazolin (7.1). Compared to cefazolin, the negative CDT RR was 16.23 (10.97-23.69; P &lt; 0.001) for metronidazole, 10.06 (7.23-13.95; P &lt; 0.001) for broad spectrum antibiotics and 8.39 (5.60-12.36; P &lt; 0.001) for vancomycin.
C difficile Negative and Positive Testing Rates in the 30-Days Following Pediatric Procedures Requiring Preoperative Antibiotic Prophylaxis, Stratified According to Prophylactic Antibiotic Category and Procedure Category Used to Select Prophylactic Antibiotic

Conclusion
The study demonstrates that CDT rates by PCR vary by procedure type and antibiotic prophylaxis regimen. Both CDI and CDT rates were higher for GI procedures. Negative CDT rates were especially high for GI procedures and for antibiotic prophylaxis with non-cefazolin containing regimens. High postoperative rates of negative CDT suggest that non-infectious diarrhea contributes to testing. These studies are relevant to diagnostic stewardship efforts aimed at preventing unnecessary CDT.

Disclosures
Abhishek Deshpande, MD; PhD, Merck: Advisor/Consultant|Seres Therapeutics: Grant/Research Support Charles B. Foster, MD, 3M Co: Stocks/Bonds|Novavax: Stocks/Bonds|Scynexis: Stocks/Bonds|Veru Inc: Stocks/Bonds|Vir Biotechnology: Stocks/Bonds
1678. Non-Invasive and invasive Pediatric Group A Streptococcus Infections (iGAS) Admissions During 2021 and 2022 at a Tertiary Health Care Center: Resurgence and Concomitant Viral Infections
Authors: Fields Susan , Butler Caroline , Chappell Sarah , Neshangi Srilatha , Camelo Ingrid 
Published: November 2023

Abstract

Background
A resurgence of invasive Group A Streptococcus (iGAS) infection in children was observed in Colorado and Minnesota by the Centers For Disease Control and Prevention (CDC) during the fall of 2022. Cases were accompanied by hospitalizations for respiratory syncytial virus (RSV) and influenza. We describe hospital admissions with iGAS and non iGAS infections at a tertiary health care center in Augusta, GA during 2021 and 2022; the only children’s Hospital with 150 licensed beds and a population of 201.196 as of 2021.

Methods
We used the iGAS definition by the CDC as a Group A Streptococcus (GAS) isolated by culture in specimens obtained from a sterile body site, or GAS isolated from wound culture and necrotizing fasciitis or streptococcal toxic shock syndrome. We conducted a retrospective chart review of iGAS and non iGAS cases admitted to the Children’s Hospital of Georgia during January to December 2021 and January to December 2022. We collected demographics, site of infection, concomitant viral infections diagnosed by nasopharyngeal (NP) PCR, intensive care unit (ICU) admission and mortality.

Results
During 2021, only 1 patient was admitted with non iGAS, a 7-year-old with a wound infection. In 2022, 15 patients were diagnosed with GAS infection, 7 of them had iGAS and 8 had noninvasive disease. We included positive peritoneal and pleural fluid, joint/bone aspirates, bronchoalveolar lavage samples, and blood cultures for iGAS. The age range for iGAS was 6-17 years and for noninvasive, 16 mo to 11 years. In 2022, 25% of noninvasive cases had concomitant influenza compared to 43% of iGAS cases. Only one patient with non iGAS tested positive for RSV. 2 patients had rhinovirus, one had adenovirus. One patient with iGAS was positive for metapneumovirus (HMPV). 57% of iGAS cases were admitted to the ICU (n=4). 50% of noninvasive cases (n=4) were admitted to the ICU. One iGAs case died. All noninvasive cases survived.

Conclusion
There was increase in iGAS and noninvasive GAS infections during 2022 compared to 2021 in our institution. iGAS was more common in older children. Of iGAS cases, the only coexisting viruses were influenza and HMPV. Most cases were seen during Fall of 2022. The cause of reappearance of iGAS and non iGAS is still unknown but believed to be related to end of mask mandates for COVID 19 infections.

Disclosures
All Authors: No reported disclosures
1680. Characterization of Ethanol Lock Use and Line Infections in Pediatric Patients with Intestinal Failure Requiring Central Venous Access
Authors: Davidge Karen , Mroczka Elizabeth , Ivy Chelsey , Nagel Jerod 
Published: November 2023

Abstract

Background
Pediatric patients with intestinal failure often require central venous line access for administration of parenteral nutrition and/or fluids, which leads to increased risk for central line associated-bloodstream infections (CLABSI). Ethanol lock therapy (ELT) has been used to reduce the risk of CLABSI in this patient population, but recent significant increases in the price of ethanol have prompted healthcare systems to explore cost-saving measures such as decreasing ELT frequency from daily to thrice weekly (TIW) or using antibiotic lock therapy as an alternative to ELT. The objective of this study was to compare the incidence and microbiology of CLABSI in pediatric patients with intestinal failure who received different lock therapies.

Methods
This was a single-center, retrospective, descriptive study that included pediatric patients who were followed by the Michigan Medicine Children’s Intestinal Rehabilitation Program between July 1, 2020 and June 30, 2022. Data were collected via the electronic health record. Incidence of CLABSI and microbiology were compared based on the type of lock therapy patients received (daily ELT, TIW ELT, or no ELT).

Results
A total of 46 patients were analyzed in this study, including 13 on daily ELT, 23 on TIW ELT, and 10 on no ELT. During the study period, 69% (9/13) of patients on daily ELT, 35% (8/23) of patients on TIW ELT, and 60% (6/10) of patients on no ELT had at least one CLABSI (for comparison between daily and TIW ELT, p = 0.0819). Of 75 episodes of CLABSI identified during the study period, the most commonly isolated pathogens were Staphylococcus epidermidis (n = 33), S. aureus (n = 19), S. hominis (n = 17), and Escherichia coli (n = 8). Almost half (44%, 33/75) of CLABSI reported were polymicrobial (see Table 1 for comparison of microbiology by type of lock therapy).Table 1:Number of monomicrobial vs. polymicrobial CLABSI by Gram stain results and type of lock therapy.

Conclusion
There was no statistically significant difference in the incidence of CLABSI between pediatric patients with intestinal failure who received TIW ELT and those who received either daily ELT or no ELT. TIW ELT appears to be an effective and cost-efficient option compared to daily ELT in this patient population.

Disclosures
All Authors: No reported disclosures
1725. Differences in serotype 3 antibody response and antibody functionality compared to serotype 19A following 13-valent pneumococcal conjugate immunization in children
Authors: Fuji Naoko , Pham Minh , Kaur Ravinder , Pichichero Michael 
Published: November 2023

Abstract

Background
Background. 13-valent pneumococcal conjugate vaccine (PCV13) includes serotype 3 and 19A. However, prevention of infections with PCV13 may be less effective against serotype 3 than 19A. In young children, determine differences in IgG antibody levels, functionality of antibody by OPA and antibody avidity for serotype 3 compared to 19A following PCV13 immunization; determine IgG antibody levels following natural immunization for serotype 3 and 19A; reassess effectiveness of PCV13 against serotype 3 and 19A in prevention of acute otitis media (AOM) and colonization.

Methods
Samples were secured during a prospective longitudinal study conducted in Rochester NY of children age 6-36 months old. Pneumococcal detection was determined by culture. 713 serum samples were tested for antibody levels by ELISA, 68 serum for functional antibody by OPA, and 47 serum for antibody avidity by thiocyanate bond disruption. Age effects on antibody levels was modeled by generalized estimating equations. PCV13 effectiveness was assessed compared to pre-PCV13.

Results
The proportion children who did not reach protective threshold against IPD (&lt; 0.35 µg/ml) after PCV13 immunization was higher for serotype 3 antibody compared to 19A. PCV13-induced antibody levels to serotype 3 were1.4 to 3.4 fold lower than 19A. OPA titers were not significantly different for serotype 3 compared to 19A, but antibody avidity at child age 6 and 15 months was significantly lower. Serotype 3 natural- immunized children showed a positive trend of increase in antibody level as children got older. In contrast, PCV13-immunized children showed a negative trend of antibody levels with age. For serotype 19A, both natural immunization and PCV13 immunization showed a positive trend in antibody levels over age. PCV13 effectiveness was not identified in preventing AOM or colonization for serotype 3 but effectiveness of 19A was re-confirmed.

Conclusion
Conclusions: PCV13 elicits lower antibody levels and lower avidity antibody to serotype 3 than 19A. PCV13 does not elicit antibody levels that increase over age despite a booster dose for serotype 3, as occurs for serotype 19A. Post PCV13-induced antibody levels for serotype 3 may be insufficient to prevent AOM and colonization in young children.

Disclosures
All Authors: No reported disclosures
1729. Literature Review to Identify Evidence of Secondary Transmission of ROTATEQ® (RV5) Vaccine Strains to Unvaccinated Subjects
Authors: Li Yuanqiu , Sun Xiaojin , Fu Yaqun , You Xuedan , Hartwig Susanne 
Published: November 2023

Abstract

Background
Rotavirus (RV) is the leading cause of severe diarrhea in infants and young children. RV vaccination is recommended by WHO since 2009 for all children worldwide, especially in countries with a high number of diarrhea-associated deaths. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of RV5 strains leading to clinical disease was not well evaluated in the pivotal clinical trials and only few case-reports have been described in the literature.

Methods
We performed a systematic literature review to investigate secondary transmission of RV5 vaccine strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers and other resources (i.e., conference papers with full text, preprint platform including bioRxiv and medRxiv) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles bases on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 vaccine strain transmission as outcomes. Other study or publication types were excluded such as pre-clinical studies, interventional studies and case reports. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used and study quality was assessed using the Newcastle Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess risk of bias.

Results
The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of NOS or JBI checklist respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms but all symptoms were attributed to other clinical conditions.

Conclusion
We found no evidence of horizontal transmission of RV5 vaccine virus strains to unvaccinated infants despite the limited amount and descriptive nature of the identified studies.

Disclosures
All Authors: No reported disclosures
1743. Health Care Resource Utilisation (HCRU) Due to Respiratory Syncytial Virus (RSV) Before the Age of Two in England
Authors: Fonseca Maria João , Bangert Mathieu , Kramer Rolf , Cirneanu Lorena , Hudson Richard 
Published: November 2023

Abstract

Background
RSV is responsible for 33 million lower respiratory tract infections (LRTI) worldwide. The highest burden occurs in infants &lt; 1 year of age during RSV season, which is from October to February in England. Due to lack of routine laboratory testing, its true disease burden is unknown. This study aimed to estimate the respiratory related primary and secondary care healthcare resource utilisation (HCRU) of RSV admissions before the age two in England.

Methods
This retrospective cohort study used Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked data to establish a birth cohort of all infants born between 01/03/2015 and 28/02/2017 (n=449,591). Case cohorts included infants under two with a hospital admission of: 1) confirmed RSV (n=4,813), 2) bronchiolitis (n=22,913), 3) any RTI (n=56,871). Each case cohort was compared with all birth cohort infants without the corresponding admission (comparative cohorts). Respiratory related HCRU (primary care, outpatient, accident and emergency [A&E], and inpatient admissions) were estimated in the month prior to and up to 24 months following the first admission in each cohort.

Results
The RSV-coded cohort had the highest HCRU overall, mean (SD) of 5.1 (4.8) admissions vs. 1.5 (2.4) in its comparative cohort (71% difference). This difference was largely due to A&E and inpatient admissions. Comparable results were found for bronchiolitis-coded and RTI-coded cohorts. The highest rates of inpatient admissions were observed for the RSV-coded case cohort, and these occurred during the calendar months of November and December. Inpatient admissions were largely among infants up to 12 months of age and included infants that were born both before and during the season (Figure 1).

Conclusion
Infants with an RSV admission had higher HCRU than infants without. Most hospitalisations occurred in November and December when services are at their most stretched. During the first year of life, the HCRU rates observed for infants born before and in the season were equally very high, emphasizing the need for preventative strategies to all infants entering their first RSV season. Funding: This research was funded by collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease.

Disclosures
Maria João Fonseca, n/a, Sanofi: Advisor/Consultant Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds Richard Hudson, n/a, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds
1780. COVID-19 Vaccine Accessibility and Uptake among U.S. Children Aged 6 Months-4 Years and 5 Years-11 Years by Domains of Social Vulnerability
Authors: Khazanchi Rohan , Rader Benjamin , Cantor Jonathan , Bravata Dena M , McManus Kathleen A , Whaley Christopher , Weintraub Rebecca , Brownstein John 
Published: November 2023

Abstract

Background
The COVID-19 pandemic, and pandemic-related interventions, have had markedly disparate effects on marginalized populations. We examined whether the inequitable distribution of other COVID-19 resources was similarly reflected within the pediatric vaccination rollout.

Methods
We analyzed from a comprehensive national database of U.S. pediatric vaccination distribution sites and administered doses (VaccineFinder) as of 7/29/2022. We ascertained accessibility by geocoding sites, measuring one-way travel times from every Census tract population center to the nearest site, and weighting tracts by population demographics (rurality, age, race, ethnicity) to obtain nationwide estimates. We used population-weighted quasipoisson regressions adjusted for state fixed effects to compare vaccination uptake between the most and least socially vulnerable quartiles of counties by Social Vulnerability Index (SVI) domains (socioeconomic status, SES; household composition & disability, HCD; minority status & language, MSL; housing type & transportation, HTT).

Results
We identified 15,233,956 total vaccine doses administered across 27,526 sites. Rural, non-Hispanic, White, and Native populations had longer one-way travel times to the nearest pediatric vaccination site than urban, Hispanic, Black, and Asian populations. Greater social vulnerability by overall SVI, SES, and HCD was associated with decreased vaccine uptake among children in the 6mo-4y (Overall: IRR 0.70 [95%CI 0.60-0.81], SES: 0.66 [0.58-0.75], HCD: 0.38 [0.33-0.44]) and 5y-11y (Overall: 0.85 [0.77-0.95], SES: 0.71 [0.65-0.78], HCD: 0.67 [0.61-0.74]) groups, whereas greater social vulnerability by MSL was associated with increased uptake in both age groups (6mo-4y: 5.16 [3.59-7.42], 5y-11y: 1.73 [1.44-2.08]).
Figure 1. Geospatial Visualization of One-Way Travel Time to the Nearest COVID-19 Vaccination Site by Age Figure 2. One-Way Travel Time to the Nearest 6mo-4y COVID-19 Vaccination Site by Race, Ethnicity, Rurality Figure 3. One-Way Travel Time to the Nearest 5y-11y COVID-19 Vaccination Site by Race, Ethnicity, Rurality

Conclusion
We identified meaningful spatial patterns in the accessibility and uptake of pediatric COVID-19 vaccinations, including decreased vaccine uptake in areas of high SES and HCD vulnerability and greater uptake in areas of high MSL vulnerability. Our modeling and surveillance approaches are generalizable and can be applied to other emerging pathogen response and scarce resource allocation efforts.

Disclosures
Dena M. Bravata, MD, MS, Castlight Health: Advisor/Consultant Kathleen A. McManus, MD, MSCR, Gilead Sciences, Inc.: Stocks/Bonds