bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1174. MBI-CLABSI Cluster in Pediatric Oncology Patients with Hematologic Malignancies Introduces New Barrier in Fluoroquinolone Prophylaxis
Authors: Jowers Karlye , Mason Matt , Gilman Margaret , Vodzak Jennifer 
Published: January 2025

Abstract

Background
Levofloxacin is preferred for prophylaxis during neutropenic periods in pediatric patients with high-risk acute myeloid and lymphoblastic leukemias (AML and ALL, respectively). The goal is to decrease risk of morbidity and mortality from bacteremia related to central venous lines (CVL) and chemotherapy-induced mucosal barrier injury (MBI), but antibacterial resistance may develop. Our institution observed an unexpected increase in MBI-central line associated bloodstream infections (MBI-CLABSI) in 2023, prompting a multidisciplinary review of the MBI-CLABSI cluster.

Methods
Retrospective chart review was performed to characterize a cluster of MBI-CLABSI events occurring in pediatric patients with AML or ALL from 2020-2023 at our 220-bed, urban/suburban, free-standing children’s hospital. Descriptive analysis of the 2023 cluster events was performed, including patient demographics, diagnosis, transplant status, pathogen and prophylactic drug data to identify commonalities and potential harm-reduction interventions.

Results
Rate of MBI-CLABSI were steady from 2020-2022 (0.24) and increased to 1.11 per 1,000 central line days in 2023 in patients with AML or ALL. Standard infection ratio of 3.69, p-value 0.0001. 85.7% (n=12/14) MBI-CLABI occurred in patients who had received prophylactic levofloxacin. Almost all organisms causing the MBI-CLABSIs were levofloxacin resistant (98%) and most (58%) were resistant to at least one additional antibiotic. Patients with multiple MBI-CLABSI events with a levofloxacin-resistant organism during the cluster year was not uncommon (66.7%; n=8/12)). . In this subset, patients continued to receive prophylactic levofloxacin despite having earlier infections caused by a levofloxacin-resistant pathogen.

Conclusion
Use of levofloxacin prophylaxis for neutropenia episodes in high-risk AML and ALL patients may increase the risk of MBI-CLABSI events with levofloxacin-resistant organisms, thus reducing the effectiveness of the prophylaxis goal to prevent serious bacterial infections and reduce harm. Further studies are needed to better delineate optimal use of prophylactic antibiotics by incorporating population-level antibiograms and patient-specific infection histories.

Disclosures
All Authors: No reported disclosures
423. Mirror Mirror on the Wall Who is Driving all the Invasive GAS After All - The Utah Experience
Authors: McMillion Benjamin , Pershing Nicole L , Crandall Hillary , Hersh Adam , Ampofo Krow , Olson Jared , Oakeson Kelly F , Wagner Jennifer M , Nielsen Shannon , Dickey Mandy , Huynh Kelly , Pavia Andrew T , Blaschke Anne J 
Published: January 2025

Abstract

Background
Streptococcus pyogenes (GAS) is a common cause of non-invasive mucosal infections as well as rare life-threatening invasive disease. At the onset of the COVID-19 pandemic there was a decline in invasive GAS (iGAS) disease, followed by an increase in the fall of 2022 with the rise of emm12. Data on the association of circulating non-invasive and invasive emm-types are limited. We sought to characterize and compare emm-types of pharyngeal GAS to iGAS before and after the emergence of COVID-19.Figure 1:Positive GAS pharyngeal culture, PCH ED and iGAS cases by Quarter, Utah Q1 2018 - Q1 2023

Methods
We retrospectively identified both pharyngeal and invasive GAS isolates obtained at Primary Children’s Hospital (Salt Lake City, Utah) from 2018-2023 using our GAS isolate database. Pharyngeal isolates were obtained primarily from our emergency department, while iGAS isolates were from hospitalized patients. Isolates underwent whole genome sequencing for emm typing, virulence factor identification, and phylogenetic analysis. We compared pharyngeal and invasive isolates for emm-type distribution over time and the presence of known virulence genes.Figure 2:Invasive and Pharyngeal emm-type Percentages, by Year, Utah 2018-2023

Results
From 1/2018 to 4/2023, we identified ∼650 pharyngeal GAS isolates, of which a random subsample of 306 were sequenced; 286 yielded sequences suitable for analysis. We identified 145 iGAS cases; all were sequenced. We observed a marked decrease in pharyngeal GAS from Q2 2020 through Q3 2022, followed by a steep increase which paralleled iGAS (Figure 1). The distribution of emm-types causing iGAS mirrored that of non-invasive pharyngeal isolates over time (Figure 2). Post-pandemic, emm12 and emm1 dominated both pharyngeal and invasive isolates. Comparing virulence genes between pharyngeal and iGAS isolates showed sfbl/prtF1 were strongly associated with invasive disease in emm12 and emm59 (OR: 5.0, 95% CI [2.2-11]) while the presence of sic was strongly associated with invasive disease in emm1 (OR: 16.2, 95% CI [5.6-45.9]).

Conclusion
After a marked decrease in GAS infections in children during the COVID-19 pandemic in Utah, there was a rebound of disease. Molecular analysis revealed invasive emm-types mirrored trends in pharyngeal isolates. Virulence genes sfbl/prtF1 and sic were associated with invasive disease in emm12 and emm1 respectively. Further analysis of evolutionary relatedness and virulence determinants is ongoing.

Disclosures
Krow Ampofo, MBChB, Merck: Grant/Research Support Andrew T. Pavia, MD, GSK/Haleon: Advisor/Consultant|Sanofi: Advisor/Consultant Anne J. Blaschke, MD, PhD, BioFire Diagnostics/Biomerieux: I have IP owned by the U. of Utah licensed to BioFire and receive royalties.|Merck & Co: Advisor/Consultant
P-1212. Enterovirus D68 (EV-D68) Incidence and Spectrum of Illness among Children 0-2 years in a U.S. Community-based Birth Cohort in Cincinnati, OH during 2017-2020
Authors: Teoh Zheyi , Midgley Claire , Quigley Christina M , Conrey Shannon C , Cline Allison R , Ostrow Amy , White Brendon , McMorrow Meredith L , Payne Daniel C , Morrow Ardythe L , Staat Mary A 
Published: January 2025

Abstract

Background
The community burden and epidemiology of non-medically attended enterovirus-D68 (EV-D68) is unknown, as prior studies focus on EV-D68-associated asthma exacerbation, pneumonia, or acute flaccid myelitis (AFM) which occurs biennially. We describe EV-D68 incidence and spectrum of illness among children 0-2 years in Cincinnati, OH during 2017-2020.

Demographic and molecular characteristics of enterovirus D68 (EV-D68) infections (n=46) in PREVAIL, 2017-2020

Methods
The PREVAIL cohort is a community-based, longitudinal birth cohort of healthy mother-infant pairs with children observed from birth to 2 years of age. Nasal swabs were collected weekly from children and tested using the PCR-based Luminex Respiratory Pathogen Panel. Swabs positive for rhinovirus/enterovirus (RV/EV) between July-December, during which the typical U.S. enterovirus season occurs, were then tested for EV-D68 by RT-PCR. Weekly text surveys and chart abstraction identified symptoms and medically attended visits. Acute respiratory illness (ARI) was defined as the presence of cough or fever within 7 days of virus detection.

Symptomatology of enterovirus D68 (EV-D68) infections (n=46), by medical attendance

Results
The PREVAIL Cohort enrolled 245 mother-infant pairs who submitted 13,781 infant nasal swabs during 04/2017-07/2020. A total of 1,424 swabs positive for RV/EV between July-December were further tested for EV-D68. Forty-six EV-D68 infections were detected, all occurring between 08/2018-11/2018; no detections occurred in 2017, 2019, or 2020. Estimated annual incidence of EV-D68 was 0.78/100 child-weeks (95%CI: 0.57-1.04) for 2018. Median age at EV-D68 infection was 7.5 months (Table 1). Of the 46 infections, 21 (46%) met ARI criteria; the remaining 25 (54%) were considered asymptomatic. Overall, cough (39%), nasal congestion (35%) or fever (26%) were the most prevalent symptoms, while diarrhea (9%) or vomiting (4%) were infrequent (Figure 1). Seven (15%) EV-D68 infections were medically attended, with 3 evaluated in an emergency department. No hospitalizations and no cases of pneumonia or AFM occurred.

Conclusion
In our community cohort of healthy children aged &lt; 2 years, less than half of EV-D68 infections met ARI criteria (46%), and 15% were medically attended; none required hospitalization. Prospective multi-year cohort studies in all ages would be valuable for understanding the full spectrum of symptoms, and burden of EV-D68.

Disclosures
Mary A. Staat, MD, MPH, Cepheid: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria
P-1213. Optimizing the synergy between Aztreonam & Avibactam for NDM plus OXA48 producing Carbapenem resistant Klebsiella pneumoniae infections: an innovative infusion method
Authors: Soman Rajeev , Gandhi Aashna , Kedare Noopur , Joe Geethu , Patil Saiprasad , Pednekar Amullya , Barkate Hanmant 
Published: January 2025

Abstract

Background
Ceftazidime-avibactam (CAZ AVI) along with aztreonam (ATM) is used off-label for NDM+OXA48 producing carbapenem resistant Klebsiella pneumoniae (CR Kp). If the level of AVI is maintained at 2.5 μg/ml, it protects ATM from OXA48 & allows it to act against such CR Kp. In such a situation the MIC to ATM has been found in a published report to be 2 μg/ml.

Table shows the measured protein bound drug levels. Estimated free drug levels are shown in brackets.

Methods
We used CAZ AVI (CAZ 2 grams and AVI 0.5 gram) infusion over 3 hours & ATM 2 grams infusion over the 2nd half an hour as shown in figure 1, in 5 patients infected with NDM+OXA48 CR Kp, as a proof-of-concept PK study. The rationale of starting the ATM infusion after the CAZ AVI infusion is begun is to allow AVI levels to build up & prevent inactivation of ATM by ESBL & OXA48. The administration of ATM over half an hour, rather than by a more prolonged infusion, may ensure a relatively high initial level of ATM, which is expected to remain for a considerable time owing to its long half life.

Infusion strategy for Ceftazidime-Avibactam (CAZ-AVI) & Aztreonam (ATM)

Results
After measurement of protein bound levels, free AVI (fAVI) & free ATM (fATM) levels were estimated from the known extent of protein binding. As shown in table 1, all levels of estimated fAVI were above 2.5 mcg/ml. The estimated levels of fATM, at 5 hours after beginning the infusion were at or above 15.6 mcg/ml, with a mean of 45.6 mcg/ml & range of 15.6 to 98.2 mcg/ml. Hence time above 4 times the assumed ATM MIC of 2 mcg/ml, for more than 50% of the dosing interval was easily achieved in all the patients.

Conclusion
Thus, the PK/PD index obtained is higher than that needed for optimal killing & can suppress resistance which may be useful from the perspective of antimicrobial stewardship.

Disclosures
Rajeev Soman, MBBS, MD (General Medicine), FIDSA, Astellas: Honoraria|Biomeriux: Honoraria|Cipla: Honoraria|Emcure: Honoraria|Gilead: Honoraria|Glenmark: Honoraria|Gufic: Honoraria|Intas: Honoraria|MSD: Honoraria|Mylan: Honoraria|Pfizer: Honoraria Saiprasad Patil, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee Amullya Pednekar, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee Hanmant Barkate, Global Medical Affairs, Glenmark Pharmaceuticals Limited: Employee
P-1215. Evaluation of Vancomycin AUC/MIC Ratio in Indian Patients with Enterococcal Infections: Impact on Clinical Outcomes and Nephrotoxicity
Authors: Sebastian Albin , Raju Jomel , Tom Maria 
Published: January 2025

Abstract

Background
Vancomycin is commonly used to treat enterococcal infections, but its optimal dosage remains uncertain in Indian patient populations. This study aimed to investigate the relationship between vancomycin AUC/MIC ratio and clinical outcomes, as well as nephrotoxicity, in Indian patients with documented enterococcal infections. Understanding this relationship is crucial for optimizing treatment strategies and improving patient outcomes in this context.

Methods
Data were collected retrospectively from medical records of 71 patients who received vancomycin with therapeutic drug monitoring at a single center in India between April 2015 and March 2022. Vancomycin AUC0–24 was calculated using a Bayesian technique, while MIC was determined using the VITEK 2 automated microbiology system. The AUC0–24/MIC ratio was computed for the initial 72 hours of therapy. Statistical analysis was conducted to assess the association between vancomycin AUC/MIC ratio and clinical outcomes, as well as nephrotoxicity.

Results
The cohort comprised 71 participants meeting the inclusion criteria. Results indicated that a vancomycin AUC/MIC of ≥400 mg·h/L exhibited significant differences in clinical response (aHR: 0.49, 95% CI: 0.21–0.98; p = 0.044) and microbiological response (aHR: 0.41, 95% CI: 0.17–1.08; p = 0.039) compared to AUC/MIC &lt; 400 mg·h/L. However, patients with AUC/MIC ≥400 mg·h/L had a higher incidence of nephrotoxicity compared to those with AUC/MIC &lt; 400 mg·h/L (aHR: 3.41, 95% CI: 1.11–15.83; p = 0.033). Elevated vancomycin concentrations may lead to declining renal function. Moreover, declining renal function could result from factors such as failure to resolve the infection focus or co-administration of other antibiotics, potentially leading to higher AUC/MIC ratios. The study identified a target vancomycin AUC/MIC of ≥400 mg·h/L, suggesting its optimality for monitoring the treatment of enterococcal infections in the Indian context.

Conclusion
In Indian patients with enterococcal infections, a vancomycin AUC/MIC of ≥400 mg·h/L is associated with improved clinical and microbiological responses but may increase the risk of nephrotoxicity. Therefore, careful monitoring of vancomycin dosage and renal function is essential to optimize treatment outcomes in this population.

Disclosures
All Authors: No reported disclosures
P-1233. Application of Pharmacometrics in the Personalized Colistin Dosing Recommendation
Authors: Seok Hyeri , Choi Suein , Han Seunghoon , Choi Won Suk , Park Dae Won 
Published: January 2025

Abstract

Background
Colistin is frequently used as a treatment for infections caused by carbapenem-resistant Gram-negative bacteria. Colistin dosing should be adjusted according to the patient's renal function because the prodrug, colistin methanesulfonate (CMS), is partially removed by the kidney. Intensive care unit (ICU) patients may require individualized dosing to prevent nephrotoxicity or treatment failure due to the highly variable pharmacokinetics (PK) of colistin.Figure 1.Example of colistin dosing recommendation program – Patient information input

Methods
Colistin plasma concentration data from ICU patients who received colistin from June 2019 to August 2022 in Korea University Hospital were included in the dataset for this population PK analysis. We developed a population PK model for colistin using ICU patients, and established therapeutic drug monitoring software. A population PK analysis was performed using the first-order conditional estimation method with interaction in non-linear mixed effects modeling. We used the open-source R Shiny program to establish Colistin TDM software. The structural PK model and the final estimates of both fixed-effect and random-effect parameters were translated into an R code.Figure 2.Example of colistin dosing recommendation program – Simulation outputRecommendations provide the loading and maintenance doses based on patient information. Maintenance dose depends on the predicted colistin trough and peak levels, and the interval and infusion time of colistin administration.

Results
We enrolled 176 colistin observations from 22 patients in the dataset. A two-compartment, first-order elimination model best described the PK of Colistin A, one-compartment, first-order elimination model for PK of Colistin B, and one-compartment, first-order elimination model for PK of CMS. In the results from the covariate analysis, GFR estimated by Cockcroft–Gault equation and albumin level was included as a statistically significant covariate of total clearance of CMS, and body weight was selected as a covariate of CMS volume of distribution. The two-compartment structure model for Colistin and CMS, the final estimates of both fixed effects and random effects from the PK model and the log-likelihood Equation (5) for estimating ηi were implemented in R script. A draft version of the software is now available at http://mychloe00.shinyapps.io/colistin_new.

Conclusion
We developed colistin TDM software using PK parameters in ICU patients for individualized colistin administration. Further research is needed to determine whether colistin is actually administered within the therapeutic range through the application of this software.

Disclosures
All Authors: No reported disclosures
P-1240. Optimal Vancomycin Model Selection for Obese Patients Receiving Outpatient Parenteral Antimicrobial Therapy (OPAT)
Authors: Couch Kimberly A , Luu Quyen , Prokesch Richard C , Adams John S , John Joseph F , Van Anglen Lucinda J 
Published: January 2025

Abstract

Background
Optimal OPAT dosing of vancomycin (VAN) is challenging in obese patients. Multiple Bayesian pharmacokinetics (PK) models to aid in AUC estimation exist, including several obesity-specific models. PK population models in the absence of drug serum levels (a priori) are useful to initiate therapy, but once drug serum levels are obtained, model performance is based upon individual patient PK (a posteriori). This study is the first evaluation of the optimal PK model for obese patients receiving OPAT.

Methods
Analysis included all OPAT patients who received VAN in 2022-2023 with at least one therapeutic drug level, and a body mass index (BMI) ≥ 30 kg/m2. Data collection included demographics, anthropometrics, treatment information, laboratory values, and AUC24. Ten PK models were used to predict VAN serum concentrations and calculate AUC24 using a Bayesian dosing software. The performance of each model was assessed using a priori root mean square error (RMSE) and a posteriori RMSE for each model. The average RMSE was also calculated for patients with BMI 30-39.9 kg/m2 and for those ≥40 kg/m2. The model with the best performance for each BMI category was reported.

Results
Of 920 VAN OPAT patients, 420 (45.6%) were identified with a BMI ≥30 kg/m2. Population characteristics are included in Table 1, with 80% having a BMI 30-39.9 kg/m2. Median duration of VAN was 23 days (IQR: 12-35). The RMSE calculations per model and BMI groups are shown in Table 2. Best model fit varied among BMI groups and is indicated in bold type. For RMSE a priori, the Crass model performed the best for BMI 30-39.9 kg/m2 and the UVM model was best for BMI ≥40 kg/m2. The RMSE a posteriori with best performance for BMI 30-39.9 kg/m2 was Thompson capped, with UVM and Goti also performing well. For BMI ≥40 kg/m2, RMSE a posteriori, the Goti model was the best performing.

Conclusion
Obesity models provided good performance for a priori predictions and performed similarly to non-obese models in a posteriori predictions. This research supports use of both obesity and non-obesity models for VAN PK in OPAT.

Disclosures
Joseph F. John, Jr., MD, FACP, FIDSA, MicroGenDx: Advisor/Consultant Lucinda J. Van Anglen, PharmD, Cumberland Pharmaceuticals: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Novartis Pharmaceuticals: Grant/Research Support|Takeda Pharmaceuticals: Grant/Research Support
P-1245. Optimizing Antibiotic Dosing in Burn Patients: Real-Time Therapeutic Drug Monitoring for Enhanced Therapeutic Efficacy
Authors: Paulson Shon , Biju Sanju 
Published: January 2025

Abstract

Background
Burn patients often receive antibiotic therapy, but optimal dosing can be challenging due to variability in pharmacokinetics. This study aimed to assess the accuracy of antibiotic dosing in burns and the impact of real-time dose adjustment via therapeutic drug monitoring (TDM).

Methods
Given the challenges in predicting pharmacokinetics in burn patients, we conducted a 3-year prospective, monocentric, randomized, controlled trial to assess antibiotic dosing accuracy and the effect of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adjustment to maintain therapeutic antibiotic concentrations. Forty-three consecutive burn patients receiving antibiotics were screened at a tertiary care hospital in India. Forty met the inclusion criteria; one declined participation, and another withdrew consent, leaving 21 patients each in the intervention and standard-of-care groups. A total of 38 infection episodes were analysed.

Results
Before the intervention, only 35 out of 67 (52%) initial trough concentrations were within the therapeutic range. No significant difference was found between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% CI, 0.81 to 2.39], P = 0.227) or the time to achieve the target concentration. However, due to real-time dose adjustments, the intervention group showed a higher proportion of trough concentrations within the predefined range (38/51 [74.5%] versus 33/58 [56.9%]; adjusted odds ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), spent more days within the target range (157 days/245 days on antibiotics [64.1%] versus 138 days/253 days on antibiotics [54.5%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and had fewer subtherapeutic trough concentrations (19/88 [21.6%] versus 32/99 [32.3%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No significant difference in infection outcomes was observed between the study groups.

Conclusion
Systematic TDM with same-day real-time dose adjustment was effective in achieving and maintaining therapeutic antibiotic concentrations in burn patients, minimizing both over- and underdosing.

Disclosures
All Authors: No reported disclosures