bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1199. The burden of respiratory syncytial virus among Brazilian infants (BONSAI study): preliminary results
Authors: Ribeiro Manoel , da Silva Rodrigo C , Ribeiro Karina , Tolardo Aline , Homsani Sheila , Barata Rita 
Published: January 2025

Abstract

Background
Respiratory syncytial virus (RSV) is a leading cause of global morbidity and mortality in children &lt; 1 year. Recent data have shown the burden of the disease among full-term babies. RSV surveillance system in Brazil does not capture information about gestational age. We aimed to estimate the incidence of hospitalization due to RSV according to gestational age among infants in Brazil.

Methods
Retrospective cohort study linking (deterministic and probabilistic, based on date of birth, city of residence, and mother´s name) the National Influenza Surveillance System (SIVEP-Gripe) and the National Information System on Live Births (SINASC). All children aged ≤24 months, living in São Paulo state, Brazil, admitted to hospitals clinically presenting with severe acute respiratory illness (SARI) tested for RSV from 2017 to 2019 were included. Incidence rates (IR) were calculated per 10,000 live births/year. Relative risk and corresponding 95% confidence intervals were estimated.

Results
During the study period, 1,807,703 live births were registered in São Paulo state and 11,003 cases of SARI, with 1,801 cases positive for RSV (16.4%). We successfully linked 1,436 RSV cases with SINASC (79.7%). IR was 7.94/10,000 live births/year, peaking in April and May. Eighty-one percent of cases (n=1,166) were registered in full-term infants (37+ weeks) (IR=7.28 cases/10,000 live births/year). IR for infants born &lt; 29, 29-31, 32-36 weeks (w) were 12.68, 19.74, and 12.84 cases/10,000 live births/year, respectively (RR, premature vs full-term=1.83; 95% CI 1.60-2.10). Forty-nine percent of full-term infants with RSV were admitted to ICU (n=570), while the figures for the other gestational age categories were: &lt; 29 (76.5%), 29-31 (60%), 32-36 w (51.8%). The case-fatality rate was 0.8% overall (4% for premature and 0.4% for full-term infants).

Conclusion
Our results showed that the burden of RSV among full-term infants is high (81% of hospitalized cases). Although the risk is higher among premature, a significant proportion of full-term infants can have unfavorable prognoses needing ICU admission, generating an overload of the healthcare system during seasonality. Preventive strategies for all infants are crucial to reduce the burden of RSV in Brazil.

Disclosures
Manoel Ribeiro, MD, PhD, Sanofi: Grant/Research Support Rodrigo C. da Silva, MSc, Sanofi: Grant/Research Support Karina Ribeiro, DDS, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Aline Tolardo, PhD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Sheila Homsani, MD, Sanofi: Employee|Sanofi: Stocks/Bonds (Private Company) Rita Barata, MD, PhD, Sanofi: Grant/Research Support
P-1225. The population Pharmacodynamics study of Ganciclovir in Thai kidney transplant recipients with cytomegalovirus infection
Authors: Chantharit Prawat , Sutharattanapong Napun , Chatupho Wasin 
Published: January 2025

Abstract

Background
The aim of this study was to describe the population pharmacodynamic (PPD) of intravenous Ganciclovir for preemptive and treatment in Thai kidney transplant recipients (KT) with cytomegalovirus (CMV) infection who were not during hemodialysis or KT-related systemic lupus erythematous.
Simulations of CMV viral load overtime according to recommended dose

Methods
A retrospective study was conducted by collecting data from medical records, from 1 January 2020-31 December 2022. The estimated pharmacokinetic (PK) parameters derived from published model were applied to link with PPD, subsequently simulate the changes of blood CMV viral load overtime according to recommended dosage, stratified by glomerular filtration rate (GFR). PK/PPD modelling, and simulation were performed with parametric methodology using Phoenix® software, version 8.4, Certara.
Visual Predictive Check

Results
Twelve patients were included. The PPD model was developed by mechanistic indirect response equation, applying Emax model to stimulate the rate of CMV clearance. There were not any significant clinical and laboratory covariates affecting CMV dynamic. Goodness-of-fit plots were acceptable. A visual predictive check showed good consistency with observed data, whereas 1000 times-bootstrapping analysis was completed with 100% success rate. Ten thousand times-simulation indicated the time required for achieving 1-log10 and 2-log10 reduction of CMV viral load by recommended dose were 7-8 days and 15.8-18.5 days respectively. Viral decline was delayed in patients with lowered GFR.
Goodness-of-fit plot

Conclusion
The developed model described Ganciclovir-CMV viral load relationship and simulation result indicating the longer time for CMV viral load reduction in patients who had lower GFR. Our analysis demonstrated that the current recommended dose is required to be reconsidered and further systematic PD study is needed.

Disclosures
All Authors: No reported disclosures
P-1235. HPLC-UV method to establish rapid therapeutic drug monitoring of voriconazole in outpatients
Authors: Yagi Yusuke , Jobu Kohei , Ishida Tomoaki , Yanagisawa Narika , Okazaki Moemi , Arakawa Yu , Yamagishi Yuka , Matsunaga Nobuaki , Hamada Yukihiro 
Published: January 2025

Abstract

Background
Voriconazole (VRCZ) has non-linear pharmacokinetics, so personalized dosing based on pharmacokinetics is important. Approximately 20% of Asians are poor metabolizers of CYP2C19. In Japan, challenges include rapid measurement of VRCZ blood levels, feedback of results to physicians, and rapid therapeutic drug monitoring (TDM). The aim of this study was to evaluate the rapid TDM implementation system for VRCZ in outpatients.

Methods
Measurement of outpatient VRCZ TDM was started at Kochi medical school Hospital in January 2024 based on the blood concentration measurement flow by LM1010 high performance liquid chromatograph (HPLC-UV, Hitachi High-Tech Science Corporation). From January to April 2024, we compared the trough values of VRCZ and the reporting time of blood concentration measurement results after sample collection using the conventional externally requested measurement method (Method A) and the measurement method we constructed (Method B). In addition, we investigated the occurrence of hepatotoxicity from the perspective of preventing adverse events.

Results
The trough concentration of VRCZ were 2.97±1.15 mg/L for method A (n=7) and 3.15±1.25 mg/L for method B (n=15) ,p=0.75. The time required to report VRCZ blood concentration measurement results was significantly shorter (Method A (n=7): 78.9±10.4 h vs. Method B (n=7): 0.44±0.02 h (p&lt; 0.05). No hepatotoxicity was observed during treatment in TDM outpatients who underwent rapid VRCZ measurement.

Conclusion
It is suggested that rapid determination of blood concentration of VRCZ by HPLC-UV will be an effective tool for TDM implementation and medical care support.

Disclosures
All Authors: No reported disclosures
P-1239. Systemic Exposure of Olorofim in Children with Invasive Fungal Infections
Authors: Cornelissen Karen , Rex John H , Zinzi Daniela , Bruggemann Roger , Wright James 
Published: January 2025

Abstract

Background
Olorofim (OLO) is a novel antifungal active vs. Aspergillus (including azole-resistant strains), resistant moulds (e.g., Lomentospora prolificans [LoPro]), and dimorphic moulds. Treatment with OLO in children with invasive fungal infection (IFI) is permitted under the Managed Access Program (MAP), where monitoring of trough concentrations is required due to sparsity of data in this population.

Methods
To be eligible for the MAP, children were aged 6 to 17 years, had an IFI infection that was shown to be or expected to be susceptible to OLO and had limited or no treatment options. Trough plasma samples (collected after an overnight fast) were sent to the central laboratory for analysis of OLO using a validated mass spectrometry assay. As a minimum, samples were taken after at least 7 days dosing and following any dose changes.
The paediatric dose was informed by a population pharmacokinetic (PK) model built using PK data from 52 adult patients with IFI. This model was used to predict systemic exposure in children aged 6 to 17 years based on PK parameters adjusted by weight. Paediatric doses were chosen based on a goal of Cmin ≥ 0.1µg/mL in over 90% of population, whilst Cmax and AUC were to be kept as low as possible. A further dose adjustment was required if OLO was given with strong cytochrome P450 3A4 inhibitors or inducers.

Results
To date, 22 children have received OLO, aged 6 to 17 years (mean = 11.0 y), with body weights of 20 to 80 kg (mean = 37.4 kg). IFIs treated include: IA (7), LoPro (4), Scedosporium spp. (4), coccidiomycosis (2), and other rare fungi (5). Trough level data are available for 19 subjects; the predicted maintenance dose resulted in trough levels ≥ 0.1 µg/mL in 15 subjects (79%). For the remaining 4 subjects (21%) OLO dose was increased. After dose adjustment (if required), observed trough plasma concentrations exceeded the threshold needed for efficacy (i.e., &gt; 0.1 µg/mL) on all sampling occasions.

Conclusion
With the relatively small population and sparse PK sampling data available, the predicted body-weight dependent doses for children aged 6 to 17 y are considered reasonable. The dose predictions will be updated as the PopPK model is refined and trough levels will continue to be monitored pending conduct of a formal paediatric study.

Disclosures
Karen Cornelissen, PhD, F2G: Stocks/Bonds (Private Company) John H. Rex, MD, F2G: Employee Daniela Zinzi, MD. Infectious Diseases Specialist, VP Clinical R&D at F2G: Stocks/Bonds (Private Company) Roger Bruggemann, Pharm, PhD, F2G: Advisor/Consultant|F2G: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support James Wright, n/a, F2G: Advisor/Consultant
P-1255. Dosing of Piperacillin in Altered Renal Function with and without Renal Replacement Therapy for Required Increased Exposition
Authors: Surat Güzin , Dohmann Emma , Scherf-Clavel Oliver , Kurlbaum Max , Hagel Stefan 
Published: January 2025

Abstract

Background
Piperacillin/ Tazobactam [TZP] is a commonly used antibiotic in critically ill and non-critically ill patients, but not lot is known about TZP pharmacokinetics in non-critically ill patients needing dose reduction due to renal impairment. While Summary of Product Characteristics [SoPC] suggests 16 g Piperacillin daily for severe infections, patients with renal impairment (CrCl &lt; 40 ml/min) are advised by the SoPC to only 8-12 g Piperacillin per day. The aim of this study was to determine the probability of target attainment (PTA), with the PK/PD target being set to unbound concentrations ≥60% of the time above 16 mg/L (MIC of increased exposure pathogen) in patients with decreased renal function especially in consideration of changed definitions on the susceptibility testing by EUCAST advising higher treatment dosing regimens for infections with Pseudomonas aeruginosa.

Methods
In this prospective two center study we measured 135 piperacillin serum concentration from 49 patients with decreased renal function to determine peak, trough and concentrations between peak and trough. Specific designed software (Monolix 2023R1) was used to develop a population pharmacokinetic model. The PTA was calculated for four groups (eGFR 40, 30 and 20 ml/min and 10 ml/min with intermitted hemodialysis) with different dosing strategies using Monte Carlo simulation (1000 patients per eGFR group). Covariates like age, sex, height, weight, eGFR, body mass index and body surface area (BSA) were evaluated.

Results
Patients with eGFR 40 and 30 ml/min reached a PTA of over 90% when following the SoPC (eGFR 20-40 ml/min: q8h, 30 min infusions) and increased their PTA to almost 100% when switching to prolonged (over 3h infusions). Patients with eGFR 20 ml/min reached a PTA of almost 90% with a q12h/ 30 min infusion dosage regimen recommended by SoPC for patients with eGFR &lt; 20 ml/min and increased their PTA by about 5% when receiving prolonged infusions (3h). Patients with eGFR of 10 ml/min and intermitted hemodialysis reached a PTA of about 93% (q12h, 30 min infusions) and would reach a PTA of almost 100 % when switching to 3h infusions.

Conclusion
Prolonged infusions increased the PTA in all groups. The results indicate adjustments for Piperacillin infusions in renal impairment.

Disclosures
All Authors: No reported disclosures
P-1260. Validation of Modified First-Order Kinetic Equation for Vancomycin Area Under the Curve Calculation in Neonatal Patients
Authors: Lien Tsung-Chi , Wei She-Yi , Husted Harlan , Taha Sahar , Ip Alice , Covarrubias Laurie , Rongkavilit Chokechai 
Published: January 2025

Abstract

Background
Current guideline emphasizes a ratio of 24 hour-area under the curve (AUC) to minimum inhibitory concentration (MIC) of ≥ 400 mg.h/L as the primary pharmacokinetic and pharmacodynamics predictor of vancomycin activity against serious methicillin-resistant S. aureus (MRSA) infections. Premature infants admitted to neonatal intensive care unit (NICU) are at high risk of Staphylococcal infections due to immunocompromised state and frequent procedures; however, the availability of vancomycin AUC calculator for this population is limited.

Methods
Neonates received vancomycin for at least 4 days between January 2018 and December 2023 with steady-state trough level were included. The modified first-order kinetic equation using population-based distributive volume (Vdf) of 0.7 L/kg and trough level were compared to the Vanc App program validated in infants aged 0 to 90 days with post-menstrual age (PMA) ≥ 25 weeks and weight ≥ 500 grams. Ratio and percentage difference of calculated AUCs between the two models were assessed, as were safety parameters, including urine output &lt; 0.5 mL/kg/hr over at least 6 hours, serum creatinine increases by 0.3 mg/dL or 1.5 times baseline, duration of culture positivity, and recurrence of same infection within 14 days.

Results
We identified 95 neonates with 56% male. The median (range) PMA was 30.1 (24.2 - 44.3) weeks, age was 21 (1 - 137) days, and weight was 1.2 (0.54 - 4.30) kg. Five cases had culture-proven MRSA infections. The average vancomycin dose was 37 mg/kg/day with median (range) duration of 7 (4 - 45) days. Acute kidney injury was identified in 2.1% of patients. Target AUC was achieved in 78% of cases. The average duration of culture positivity was 2.2 days, and no patients exhibited recurrent infections within 14 days after stopping vancomycin. The median (IQR) accuracy was 0.98 (0.95 - 1.01), and bias was -0.02 (-0.05 - 0.01). To obtain concordant AUC results, the mean (SD) Vdf was 0.67 (0.09) L/kg. No statistically significant differences between the two models in identifying AUC outside of therapeutic range (p=0.083).

Conclusion
The modified first-order kinetic equations can achieve comparable AUC estimates in neonates by incorporating a population PK-based VDf of 0.7 and single trough level, eliminating the need for additional blood draws.

Disclosures
All Authors: No reported disclosures
P-1277. Impact of Common Biases on Simulated Relative Vaccine Effectiveness Estimates: Implications for Evidence Synthesis, Decision Making, and Real-World Studies
Authors: Harris Daniel , Loiacono Matthew M , Chit Ayman , Oganisian Arman , van Aalst Robertus 
Published: January 2025

Abstract

Background
A growing number of real-world studies are using health administrative data to estimate relative vaccine effectiveness (rVE) due to ease of access and lower cost. To inform evidence-based decision making, meta-analyses of rVE estimates are often employed to summarize the volume of studies; however, low statistical power, unmeasured confounding, and publication bias threaten the validity of meta-analyzed estimates. Our objective was to demonstrate the impact of these biases on meta-analyzed rVE estimates using simulation.

Methods
We simulated a binary, enhanced vs. standard influenza vaccination strategy (allocated ∼1:1) and rare binary outcome (&lt; 1.0%). True rVE was 20% (1–risk ratio [RR]=0.80). To simulate observational studies, weak negative confounding due to age (RR=1.02) and strong negative confounding by indication (RR=2.0) were introduced as measured and “unmeasured” confounders, respectively. Generalized linear models (link=log; distribution=binomial) estimated RRs and 95% profile confidence intervals (CI). To assess statistical power, small (N=5,000-10,000) and large (N=100,000-150,000) “studies” were conducted. Meta-analysis pooled rVEs by study design and size (randomized [30 small; 30 large]; observational [30 small; 30 large]). To emulate publication bias, statistically significant rVEs were pooled separately.

Results
Vaccine effectiveness point estimates varied widely in small samples (e.g., randomized rVE range = 42% to -18%; observational rVE range = 36% to -78%). Large, randomized studies were unbiased and precise on average (pooled rVE=21%; 95%CI=20-23), while large observational studies were biased and precise (pooled rVE = -4%; 95%CI=-2 to -6). Pooled rVE estimates from small and statistically significant randomized studies overestimated true rVE (n=2; pooled rVE=41%; 95%CI=19-57). Pooling all studies underestimated true rVE (n=120; pooled rVE=4%; 95%CI=3-5).

Conclusion
Low statistical power, confounding, and publication biases contributed to biased, pooled rVE estimates in this simulation. Public health decision-makers using meta-analyses should be aware of these threats to validity. Additional guidance to identify/address these potential biases in meta-analysis are needed.

Disclosures
Daniel Harris, PhD, MPH, Sanofi Vaccines: Advisor/Consultant Matthew M. Loiacono, PhD, MSc, Sanofi: full-time employee|Sanofi: Stocks/Bonds (Public Company) Ayman Chit, MBiotech, PhD, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds (Public Company) Robertus van Aalst, PhD, MSc, Sanofi: Employee|Sanofi: Stocks/Bonds (Public Company)
P-1281. A Novel Substance Use Disorder-Focused Infectious Diseases Consultation Service: Our Experience with Xylazine-Related Ulcers
Authors: Novick Elizabeth , Kramer Carolyn , Zurlo John , Coppock Dagan , Seval Nikhil , Tucker Mollie 
Published: January 2025

Abstract

Background
Xylazine is a non-opioid analgesic that has become a prevalent additive in the illicit drug supply due to its low cost and synergistic effect with opioids. It is associated with soft tissue ulcers that become necrotic and can lead to infection, amputation, and death. Our hospital created a novel Infectious Diseases (ID) consultation service to help manage xylazine-related ulcers and other infectious sequelae of substance use disorder (SUD). Herein we describe characteristics of patients with SUD who presented to our hospital with xylazine-related soft tissue ulcers.

Methods
Using data extracted from our electronic health record, we generated a database of patients seen on our ID-SUD service between October 10, 2023 and January 1, 2024. We identified patients ≥ 18 years with documented SUD and conducted a retrospective chart review to identify patients with ulcers. Ulcers were defined based on documentation within the physical examination of a provider’s note or under the photographic media section. Patient demographics and clinical characteristics were collected and described using simple counts and frequencies.

Results
We identified 193 patients with SUD seen by the ID consult team during the study period. 73 patients (38%) had skin ulcers. The ulcer group was younger with a median age of 40, more likely to be white (78%) or Hispanic (18%), more likely to have tested positive for fentanyl (96%), more likely to inject (99%), and more likely to leave the hospital against medical advice (38%) compared to the non-ulcer patients, as shown in Table 1. Of patients with ulcers, 39 (53%) had ulcers &gt;10cm in size, 55 (75%) had multiple ulcers, 10 (14%) had fever on admission, 17 (23%) developed bacteremia during hospitalization, and 72 (99%) received antibiotics during hospitalization, as shown in Table 2.

Conclusion
Xylazine-related skin ulcers have become common in patients with SUD, in particular intravenous opioid use. In our adult population in a large city with high rates of SUD, we demonstrated that many patients develop multiple large ulcers. Additionally, many patients with ulcers had evidence of systemic infection with fever, leukocytosis, and/or bacteremia. We anticipate an improvement in clinical outcomes as more is learned about pathophysiology and treatment of xylazine-related ulcers.

Disclosures
All Authors: No reported disclosures
P-1321. The Infectious Disease Needs of Adult Ukrainian Refugees in a Tertiary Centre in the West of Ireland
Authors: Quirke Siobhan , Duffy Lisa , Walsh Ellen , Keane Mary Bohan , Scarry Margaret , Boyle Nicola , Langan Catherine , McDonough Katie , Tuite Helen , Gallagher David , Moloney Geraldine , Lee John , Fleming Catherine 
Published: January 2025

Abstract

Background
Since February 2022 6.5 million have fled Ukraine; 104’ 870 to Ireland (2% of Irish population) [1, 2] The surge in those seeking temporary protection, coupled with infectious disease epidemiology in Ukraine; high prevalence of blood borne viruses and TB has placed strain on host countries' health services. [3, 4] 18 ‘840 (18% of National total, 0.37% of Irish population) are accommodated within our catchment area. The objective of this study was to evaluate case complexity, barriers to access and impact on service by this population.
HIV, HCV and HBV prevalence, control and management

Methods
We performed a retrospective chart review using our electronic patient record, compiled data on a protected spreadsheet and results were collated.
Tuberculosis prevalence, susceptibility, site and management

Results
123 adult Ukrainian refugees have newly attended our service since February 2022 - April 2024, 2.03 new patients weekly; 63/123 (51.2%) are female. The mean age is 44.7 years (18 - 79). 76 (61.8%) have HIV (PLWH); 68 (89.5%) known diagnoses; 39 (57.3%) of whom were virally suppressed on ART and 27 (40%) were viraemic as a result of treatment interruption, 2 (2.9%) had no blood testing with us. 7 (5.7%) were newly diagnosed following arrival to Ireland; 4 (57%) with advanced disease (mean CD4 Count 285 IU/mL [28 - 753]). Thirty two (42%) PLWH are co-infected with HCV, 4 (5.3%) with HBV. 37 (30%) attended with HCV mono-infection, 9 (7.3%) with HBV mono-infection. 17 PLWH (22.4%) report previously treated TB. We have seen 4 (3.25%) cases of active TB; three of MDR pulmonary disease and results are pending for the fourth case. 4, 10.5% of women living with HIV in this cohort have had pregnancies; 2 (5.3% of WLH) are currently pregnant (both live in Donegal; average 165.6 miles from clinic). The average distance traveled to our clinic is 64.6 miles (Range 0.62 - 189); based on current geographic distribution of the group 50.4% (62/123) can access public transport that would allow them to reach our clinic within 2 hours. There was no significant association between access to public transport and missed clinic appointments (p = 0.64). 115/123 (93.5%) have a need for an interpreter. Since February 2022 26 (21%) have required hospital admission with an average length of stay of 22.9 days and a total of 597 bed days used.

Conclusion
We have identified significant case complexity and ongoing high ID service need for this cohort.
Cohort Demographics

Disclosures
All Authors: No reported disclosures