bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1146. Environmental Surfaces in Healthy Households as Reservoirs of Extended-Spectrum Cephalosporin-Resistant Enterobacterales in the Community
Authors: Babbs Catherine , Breeze Barrett , Boyle Mary G , Babiker Ahmed , Heidbreder Ainsley , Green Stefan J , Fritz Stephanie A , Logan Latania K 
Published: January 2025

Abstract

Background
Community-acquired extended-spectrum cephalosporin resistant (ESCr)-Enterobacterales (E) are increasing in healthy populations, yet the sources of acquisition are unknown. We assessed household (HH) environmental surface samples (HS) in St. Louis, MO, to identify the surfaces most frequently contaminated with ESCr-E and the associated mechanisms of antibiotic resistance (AR).
Figure 1. Enterobacterales within households.

Methods
From 139 HHs, samples from 21 HS and inguinal fold (IF) samples of healthy adults and children were cultured for bacteria. Families were recruited from outpatient pediatric settings. Bacterial identification and antibiotic susceptibility testing were conducted (Vitek®2, bioMérieux). Molecular characterization of ESCr-E was performed by PCR detection of beta-lactamase (bla) and plasmid-mediated quinolone resistance (PMQR) genes. Whole genome sequencing (WGS) was performed on select HH with &gt; 1 colonized HS to evaluate for genetic relatedness, plasmids, and AR genes. A HH cluster was defined as &lt; 15 single nucleotide polymorphism differences between 2 isolates.
Figure 2. ESCR Enterobacterales by genera

Results
Of 581 IF and 2801 HS, the majority harbored bacteria (IF, 97-100% and HS, 79-100%) and gram-negative bacteria, (IF, 72-80% and HS, 75-87%). IF colonization with Enterobacterales was ∼23% and ranged from 7-60% on HS; The most common ESCr-E genera were Enterobacter (79%), Pantoea (10%), and Klebsiella (7%). ESCr-E were found in 2% of IF. HS most notably colonized with ESCr-E were the kitchen sink faucet (9%), oven door handle (4%), sofa (4%), bathroom sink faucet (3%) and bed sheets (3%), (Figures 1-3). ESBL-E were recovered from ∼2% of HHs. MDR-E (&gt; 3 antibiotic classes) were found in 4% of HHs.
WGS of 20 E. cloacae from 4 HHs revealed within HH clusters (Figure 4). Of interest, we found that among E. cloacae, 10/20 (50%) contained AR plasmids (ex. IncFI, IncFII, IncX5, IncHI2, Col440I); bla, other AR (ex. PMQR, aminoglycoside, sulfa, fosfomycin) and virulence genes were detected in E. cloacae in all HHs. We also found related E. cloacae strains in 2 HHs (ST108), indicating local strains circulating potentially related to a common exposure.
Figure 3. AR Enterobacterales by surface.

Conclusion
ESCr-E are present in healthy household environments. Future directions will be to identify candidate clinical and epidemiological features linked with ESCr-E HH colonization.
Figure 4. Genetic relatedness among household Enterobacter cloacae

Disclosures
Ahmed Babiker, MBBS, Beckman Coulter Inc.: Advisor/Consultant
P-1154. Epidemiology of pediatric invasive infections in a tertiary university hospital, 2014-2023, Daejeon, Republic of Korea
Authors: So Hyejin , Kim Kyung Min , Cho Eun Young 
Published: January 2025

Abstract

Background
In early 2010s, vaccines against pneumococcus and H. influenzae have been introduced in Korea as a national vaccination, reducing the burden of pediatric invasive disease in the community. However, invasive infections in children and adolescents with underlying diseases remains important and to provide effective antibiotic treatment is essential.

Methods
To search the epidemiology of invasive infection in children and adolescents, we analyzed culture results from sterile body fluids (blood, cerebrospinal fluid, pleural fluid, joint fluid) of aged 1 month through 18 years who were hospitalized in a tertiary university hospital in Daejeon from 2014 to 2023.

Results
A total of 205 pathogens were cultured, most of which were isolated from patients with underlying diseases. Among the strains, 62% were Gram-positive bacteria, 36% were Gram-negative bacteria, and 3% were fungi. Among the 126 Gram-positive bacteria, 48 (38%) were S. aureus, 29 (23%) were coagulase negative staphylococci, 18 (14%) were enterococcus, and 3 isolates were S. pneumoniae. Among 73 Gram-negative bacteria, 22 were E. coli (30%), 19 were K. pneumoniae (26%), and 2 Salmonella were isolated. Among S. aureus, methicillin and clindamycin resistance were 52% and 48%, respectively, while vancomycin-resistance was not found. Among E. coli and K. pneumoniae, 42% of isolates were ESBL-producing strains. Resistance to cefotaxime, piperacillin/tazobactam, carbapenem were 49%, 20%, 5%, respectively.

Conclusion
Bacterial cultures in children and adolescents remains very important since it provides antibiotic susceptibility data, leading to appropriate treatment. Surveillance of invasive infections in children and adolescents should be continued in the era of increasing antibiotic resistance.

Disclosures
All Authors: No reported disclosures
P-1163. The Efficacy and Safety of Tosufloxacin in the Treatment of Bacterial Infections in Children: Systematic Review
Authors: Yong Suyun , Yang Mengjie , Zhou Mi 
Published: January 2025

Abstract

Background
In recent years, the use of antibiotics in pediatric patients has garnered significant attention due to the rise in drug-resistant bacteria. Tosufloxacin(TFLX) was used in pediatric pneumonia, otitis media, cholera, and anthrax. However, the limited use of TFLX in children is attributed to its adverse effects on bones and muscles. This article retrospectively analyzed the effectiveness and safety of TFLX in treating bacterial infections in children.

Methods
A comprehensive search was conducted on PubMed, Web of Science, and Embase, up to March 2024. Data regarding the pharmacokinetics, efficacy, and safety of TFLX use in children were included.

Results
A total of 26 articles were involved, indicating that the pharmacokinetic outcomes of 222 children with infectious diseases were significantly correlated with their body weight following administration of 4 or 6mg/kg of TFLX. The incidence of adverse reactions was associated with AUC and Cmax levels, where higher values of these parameters corresponded to increased adverse reactions. Notably, TFLX exhibited promising efficacy against MRMP, potentially surpassing macrolides, with minocycline showing superior efficacy compared to TFLX. Real-world data revealed a 100% clinical efficacy of TFLX in treating bacterial pneumonia in children. Moreover, a study involving 172 children with otitis media reported 97.7% and 94.1% clinical effectiveness rates for 4mg/kg and 6mg/kg doses of TFLX, respectively. Similar conclusions were drawn across various studies. Children under 2 years old, due to their functional and immune immaturity, benefitted from TFLX treatment for otitis media. The drug also demonstrated efficacy as a secondary option for children with refractory otitis media. Safety assessments highlighted diarrhea as the primary adverse reaction associated with TFLX, with minimal joint-related adverse effects. Some studies indicated a higher incidence of adverse reactions with 6mg/kg compared to 4mg/kg doses, suggesting a dose-dependent relationship. Overall, TFLX exhibited a good safety profile in pediatric infection management.

Conclusion
The application of TFLX in children with pneumonia and otitis media may be safe and effective, but its efficacy in MRMP is weaker than that of minocycline.

Disclosures
All Authors: No reported disclosures
P-1180. Nuanced NICUs: developing neonatal intensive care unit infection prevention and control training for health departments
Authors: Prestel Christopher , White Katelyn , Shugart Alicia , Penna Austin R , Weems Raven , Weil Lauren , Kuhar David , Sinkowitz-Cochran Ronda 
Published: January 2025

Abstract

Background
Neonatal intensive care units (NICUs) provide life-sustaining care to premature neonates and infants with complex medical needs. NICU patients are at high risk for healthcare-associated infections (HAIs) and require nuanced infection prevention and control (IPC) strategies due to unique care requirements and medical equipment. Health departments are key in providing IPC technical assistance to NICUs for outbreak response and quality improvement initiatives; however, many health department personnel are unfamiliar with NICU settings. We created and delivered NICU-specific IPC training to help health departments improve their capacity to support NICUs.

Methods
CDC developed three NICU-specific IPC educational webinars for health department personnel covering NICU settings, care, neonatal physiology, IPC practices and their nuances, and select NICU outbreak case reports. Health department personnel submitted demographic information and registered for the course electronically. Participants voluntarily responded to polls during webinars; questions included level of comfort, job duties, and NICU IPC concerns.

Results
A total of 562 individuals enrolled in the course with 469 (84%) representing 59/64 (92%) of CDC-funded health department jurisdictions across the U.S.; most enrollees (59%) currently work in a non-IPC role (e.g., epidemiologist, program lead, data analyst). Most had five years or less time in their current role (84%), including 18% with less than a year of experience; 47% reported never providing technical assistance to a NICU in the past. Among poll participants (55%) reported being unaware of how many NICUs are in their jurisdiction. HAI risk associated with medical devices (46%), hand hygiene (20%), and environmental (19%) issues were perceived as the greatest IPC concerns in the NICU. After two of three training sessions, 94% of participants felt more confident providing IPC support to a NICU.

Conclusion
Educational and training courses like these are an efficient way to improve health department capacity in providing IPC technical assistance to NICUs, and can help to build partnerships with healthcare facilities by strengthening infection prevention and quality improvement initiatives.

Disclosures
All Authors: No reported disclosures
P-1194. Comparison of COVID-19 inpatient burden in hospitalized children age &lt; 5 years, by SARS-CoV-2 variant
Authors: Andersen Kathleen M , Porter Thomas M , Reimbaeva Maya , McColgan Maria , Lopez Santiago M C 
Published: January 2025

Abstract

Background
COVID-19 disease severity has fluctuated with emergence of variants. To investigate disease severity in children, we analyzed clinical resource utilization among children hospitalized for COVID-19 during different variant periods in the United States.

Methods
We constructed a cohort of children age &lt; 5 years hospitalized for COVID-19 (ICD-10-CM code U07.1 “COVID-19”) using PINC AI Healthcare Data, a hospital-based real world data source from the United States. Hospitalizations in pre-Delta (April - June 2021), Delta (July - December 2021) or Omicron (January 2022 – July 2023) variant periods were included. We examined pre-existing conditions, hospitalization length of stay (LOS), supplemental oxygen (O2), admission to and number of days in the intensive care unit (ICU) and receipt of invasive mechanical ventilation (IMV). P-values for 3-way comparisons were calculated using Chi-square tests for proportions and Kruskal-Wallis for medians.

Results
Of 10,316 children hospitalized for COVID-19, the majority occurred in the Omicron period (n=7,767, 75%) followed by Delta (2,241; 22%) and pre-Delta (308; 3%) periods (Table 1). The age, sex, race and ethnicity distribution of cases was similar between Delta and Omicron eras. Rheumatologic and other inflammatory conditions were more prevalent during pre-Delta; otherwise, the prevalence of pre-existing health conditions was generally similar across each variant wave (Table 2). Among the following outcomes, there were no significant differences across the variants: supplemental O2 (13% pre-Delta, 16% Delta, 18% Omicron, p = 0.06), LOS (median 2 days), proportion requiring ICU care (20-21%, p = 0.77), days in ICU care (median 1 pre-Delta, 2 Delta and Omicron) and proportion requiring IMV (6-8%, p = 0.35) (Table 3). Deaths were more common in the Delta (0.9%) than pre-Delta (0.7%) or Omicron (0.4%) eras.

Conclusion
Similar disease severity was observed among children age &lt; 5 years hospitalized for COVID-19 during pre-Delta, Delta and Omicron periods. Although in-hospital death was more common with Delta, Omicron led to increased hospitalizations, highlighting the importance of continued preventative measures to prevent SARS-CoV-2 infection in children, including routine immunization.

Disclosures
Kathleen M. Andersen, PhD MSc, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Thomas M. Porter, MPH, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Maya Reimbaeva, MS, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Maria McColgan, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Santiago M.C. Lopez, MD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company)
P-1230. Dose-Escalation Study to Evaluate the Pharmacokinetics and Safety of Single and Repeat Doses of Ceftibuten in Healthy Participants
Authors: Dorr Mary Beth , de Oliveira Carlos Fernando , Lowe Kathryn , Winchell Gregory A , McGovern Paul 
Published: January 2025

Abstract

Background
Venatorx is developing ledaborbactam etzadroxil (LED-E), the prodrug of the active β-lactamase inhibitor ledaborbactam, in combination with ceftibuten (CTB), to address an unmet medical need for new oral (PO) agents to treat serious infections caused by drug resistant pathogens. Cis-CTB is the highly active isomer of CTB. The purpose of this study was to evaluate the pharmacokinetics (PK) and safety of CTB in healthy adult subjects at potential doses to be studied in combination with LE.

Methods
Thirty-six participants (PT), 12 per cohort (CTB 9, placebo, PBO 3) received a single PO dose of CTB (400, 800, or 1200mg) or matched PBO on Day 1. Following a one-day washout period, the same PT received repeat PO doses of CEF (400mg daily, 400mg q12h, or 400mg q8h) for 10 days. Serial blood samples and urine were collected for determination of single dose and steady-state plasma PK and urinary excretion of cis- and trans-CTB. Safety was assessed by recording adverse events, and changes in safety laboratory, vital signs, and ECGs.

Results
Geometric mean (%CV) cis- and trans-CTB PK parameters for single and multiple doses are shown in Table 1. AUC(0-τ) and AUC∞, appeared to increase in a dose proportional manner, while maximum concentrations (Cmax) appeared to increase in a less than dose proportional manner across the entire dose range in the single dose part of the study. Low levels of accumulation of cis-CTB were observed at steady state, with the highest accumulation ratio of 1.24 in the 400mg q8h cohort. Cis-CTB and trans-CTB recovery in urine was 47% and 6% following a 1200mg single dose, respectively.
The incidence of treatment-emergent adverse events (TEAEs) was comparable between the CTB and PBO groups across cohorts. Of the 36 PT, 25 (CTB 67%, PBO 78%) reported 65 TEAEs. Nausea, headache, and fatigue were the most reported TEAEs in CTB-treated participants. TEAEs occurring in &gt; 1 PT receiving CTB are listed in Table 2. No significant changes were noted in clinical labs, ECGs, or vital signs, and there were no serious AEs, drug-related discontinuations, or deaths.

Conclusion
Cis-CTB exposure (AUC) increased in a dose proportional manner. Single doses of CTB up to 1200 mg and multiple doses of CTB up to 400mg doses q8h for 10 days were safe and well tolerated.

Disclosures
Mary Beth Dorr, PhD, Merck: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Venatorx: Stocks/Bonds (Private Company) Carlos Fernando de Oliveira, MD, PhD, MS, Venatorx Pharmaceuticals: Stocks/Bonds (Private Company) Kathryn Lowe, MS, Venatorx Pharmaceuticals: Stocks/Bonds (Private Company) Gregory A. Winchell, PhD, Certara: Advisor/Consultant|Merck: Stocks/Bonds (Public Company)|Venatorx: Advisor/Consultant Paul McGovern, MD, Venatorx Pharmaceuticals, Inc.: employee|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds (Private Company)
P-1256. Pharmacokinetic/Pharmacodynamic (PK/PD) Target Attainment Analyses for Aztreonam-Avibactam Dosing Regimens
Authors: Raber Susan R , Xie Rujia , Soto Elena , Leister-Tebbe Heidi 
Published: January 2025

Abstract

Background
Aztreonam-avibactam (ATM-AVI) is a fixed-ratio β-lactam/β-lactamase inhibitor recently approved in Europe for adults with serious Gram-negative infections. Prior to commercial availability of ATM-AVI, doses for ceftazidime-avibactam (CAZ-AVI) + ATM have been proposed.1 We evaluated probability of joint PK/PD target attainment (PTA) for ATM-AVI and CAZ-AVI + ATM in adults with complicated intra-abdominal infection (cIAI).

Methods
A simultaneous population PK model for ATM and AVI was developed using data from the CAZ-AVI and ATM-AVI adult clinical programs, including two ATM-AVI phase 3 trials. The final model was used to simulate exposures and calculate PTA (5000 patients/simulation) for ATM-AVI dose regimens adjusted for renal function, and two proposed CAZ-AVI + ATM dose regimens in cIAI patients with CrCL 80 to ≤150 mL/min. PTA was calculated for the joint PK/PD target of ATM 60% fT &gt; 8 mg/L and AVI 50% fT &gt; 2.5 mg/L.

Results
The analysis included 4,914 ATM plasma samples (431 subjects) and 18,222 AVI samples (2,635 subjects). The final model was a two-compartment model for ATM and AVI with zero-order infusion and first-order elimination. Standard allometric exponent functions of body weight on clearances (0.75) and volumes (1) were applied; body surface area-normalized CrCL was used to describe clearance changes during treatment. Infection type was a key covariate on clearance and volume for both drugs. Steady-state exposures for ATM-AVI dose regimens were associated with joint PTA 89 to &gt; 99% across renal function groups (Table 1). CAZ-AVI + ATM dose regimens resulted in similar (or higher) geometric mean ATM Cmax,ss and AUC24,ss compared with ATM-AVI, but AVI AUC24,ss was approximately 25% lower, and joint PTA was &lt; 85% (Table 2).

Conclusion
ATM-AVI dose regimens achieved high joint PTA across renal function groups. In contrast, joint PTA with proposed CAZ-AVI + ATM dose regimens for normal renal function were &lt; 85% because of insufficient AVI exposures, regardless of the ATM dose (2g q6h or q8h). Joint PTA with both combinations is driven by the AVI plasma PK/PD target and is independent of pathogen MIC up to 8 mg/L.
1. Tamma PD et al. Clin Infect Dis 2023: ciad428.
Trial registration: NCT03329092; NCT03580044. Study sponsored by Pfizer.

Disclosures
Susan R. Raber, PharmD, MPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Rujia Xie, PhD, Pfizer: Former employee|Pfizer: Stocks/Bonds (Public Company) Elena Soto, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Heidi Leister-Tebbe, BSN, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-1264. Explore The Pharmacokinetic/pharmacodynamics Target Attainment (PTA) of cefoperazone/sulbactam
Authors: Huang Yu-Ting , Wu Chien-Chih , Huang Chih-Fen , Huang Chun-Ta 
Published: January 2025

Abstract

Background
Cefoperazone/sulbactam (CPZ/SUL) are broad-spectrum antibiotics. Current dosage guidelines consider the renal elimination characteristics of SUL. However, with the risk of antimicrobial resistance, whether current dosage recommendation of CPZ/SUL achieves the desired probability of target attainment (PTA) is unclear. The purpose of this study is to compare the PTA between adjusted-dose (AD) CPZ/SUL and standard-dose (SD) CPZ/SUL therapy.

Methods
This observational study was conducted in a tertiary hospital in Taiwan during November 2023 to March 2024. Patients using CPZ/SUL (1:1 ratio) were prospectively enrolled. Two blood samples were collected during the dosing interval to measure CPZ and SUL concentrations by using ultra-high performance liquid-chromatography. Concentrations at the middle of the dosing interval (Cm) and before dosing (Ct) were calculated based on measured concentration. PTA was represented by the fraction of time the free concentration was above the minimum inhibitory concentration (fT &gt;MIC). 50% fT &gt;MIC was defined as Cm &gt;MIC, and 100% fT &gt;MIC was defined as Ct &gt;MIC. AD group was defined as reduced CPZ/SUL doses according to the labeling, while SD group had no dose adjustment despite renal impairments.

Results
A total of 37 patients were enrolled (59.5% male, mean age, 75.4±16.0 years). The most common indication of CPZ/SUL was pneumonia (83.8%). There were 26 patients (70.3%) in the AD group and 11 patients (29.7%) in the SD group. The proportion of patients with 100% fT &gt;MIC was lower in the AD group, as compared to the SD group (CPZ: 15.4% versus 54.5%, P&lt; 0.01; SUL: 11.5% versus 72.7%, P&lt; 0.01). Additionally, 7.7% of patients in the AD group compared to 45.5% of patients in the SD group achieved 100% fT &gt;MIC for both CPZ and SUL (P&lt; 0.01). Thirty patients (81.1%) received weekly vitamin K to prevent CPZ-related coagulopathy, and none had an international normalized ratio above 2.

Conclusion
PTA was inadequate in patients receiving CPZ/SUL based on current dosage adjustment recommendations. Future investigation is needed to determine if inadequate PTA is linked to worse clinical outcomes, especially in resistant pathogens.

Disclosures
All Authors: No reported disclosures
P-1303. Moving Research into Action: The Use of Hospital Admission Data as a Measure of Ukrainian Child Migrants’ and War Refugees’ Health Needs in the First 100 Days of the War
Authors: Lewtak Katarzyna , Kleszczewska Dorota , Dzielska Anna , Mazur Joanna , Sochoń-Latuszek Agnieszka , Kukuła Katarzyna 
Published: January 2025

Abstract

Background
Since the start of the war in Ukraine on February 24th, 2022, Poland has been one of the countries with the largest arrival of migrant and war refugees from Ukraine. As the presence of Ukrainian migrant and war refugee children has increased in Poland, studies of their health condition and the use of health services have become of key importance in fulfilling their unmet health needs.

Methods
Data on the hospitalization of Ukrainian pediatric patients in Polish hospitals come from the Nationwide General Hospital Morbidity Study (NGHMS). The analyses were based on the diagnoses and conditions most responsible for the patient’s stay in hospital and coded in accordance with ICD-10.

Results
According to the NGHMS, during the first 100 days of war 2,544 Ukrainian children and adolescents under 18 years of age were admitted to Polish hospitals.
The most frequently reported hospital events among the Ukrainian migrant children were infectious and parasitic diseases (A00-B99) – 24.1%, mainly viral and other specified intestinal infections (A08; 49.3%), other gastroenteritis and colitis of infectious and unspecified origin (A09; 36.2%). Symptoms, signs and abnormal clinical and lab findings (R00-R99 – 17.8%) were the second most frequently reported cause of hospitalization, the majority of which were related to digestive system symptoms - mostly nausea and vomiting and abdominal pain, as well as fever of unknown origin. Diseases of the respiratory system (J00-J99) ranked as the third leading cause of pediatric hospitalization (12.2%), with a predominance of acute bronchitis (J20) and influenza due to identified seasonal influenza virus (J10). 88 Ukrainian children were admitted to hospital due to COVID-19. One third of analyzed hospitalizations (33.1%) had a principal diagnosis of vaccine-preventable disease (VPD).

Conclusion
Our findings suggest a greater focus on preventive healthcare and public health interventions, especially in the area of VPD. As vaccination should be considered a health equity intervention, the tailored vaccination program SAY YES TO VACCINATION in collaboration with UNICEF (SBC Office) has been implemented to increase mothers’ vaccination literacy and address gaps in vaccination coverage among Ukrainian children in Poland.

Disclosures
All Authors: No reported disclosures