bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1142. Evaluating Ambulatory Antibiotic Prescribing for Respiratory Infections at a Pediatric Institution
Authors: Yu Diana , Vaz Louise E , Nolt Dawn
Published: January 2025

Background

Over 85% of antibiotic prescribing occurs in outpatient settings such as emergency departments (ED), urgent care centers (UCC), and primary care clinics (PCC); almost half of antibiotics are prescribed for respiratory infections (RI). Given the rise of telehealth visits (TH) in both UCC and PCC settings in the past several years, this study examines the effect of location sites on antibiotic prescribing for RI at our institution.

Methods

Single-center, retrospective cohort study in Portland, Oregon, USA. Patients < = 20 years of age seen in the ED, UCC, and PC settings between 1/1/2019-12/31/2024, were included. Electronic data included age, race, ethnicity, location and encounter type, payor status, visit ICD-10 codes, and antibiotic prescription details. Multivariate logistical regression determined the effect of patient factors on antimicrobial prescribing.

Results

A total of 157,499 ambulatory encounters were included of which 24,236 were respiratory ICD10 code-related visits. Respiratory visit rates were not significantly different between non-Hispanic White and Hispanic/non-White children or by age group. RI were categorized as viral (57.7%), possible bacterial (37.6%), or co-infection (4.7%); antibiotics were prescribed 5.3%, 60.4%, and 62.8% of visits respectively. The rate of antibiotic prescribing for viral and possible bacterial RI was not different between non-Hispanic White and Hispanic/non-White children or between payor status. For viral RI, PCC and UCC settings were more likely to prescribe antibiotics compared to the ED (OR 1.4 and OR 2.36, respectively). Furthermore, PCC and UCC were less likely to prescribe narrow-spectrum antibiotics for possible bacterial RI compared to the ED (OR 0.84 and OR 0.79, respectively), including TH PCC and TH UCC visits (OR 0.29 and OR 0.56, respectively).

Conclusion

Pediatric patients with RI can receive ambulatory care through multiple settings. PCC TH (although a small percentage of all RI visits) shows the highest use of antibiotics for viral RI and the least narrow spectrum antibiotic prescribing for presumed bacterial RI. Efforts to reduce antibiotic use in viral RI should focus on non-ED settings, including TH. Strategies to encourage use of narrow-spectrum activity agents for RI should be shared with all departments.

Disclosures

All Authors: No reported disclosures
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

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 > 1 colonized HS to evaluate for genetic relatedness, plasmids, and AR genes. A HH cluster was defined as < 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 (> 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

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

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

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 < 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

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 < 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 < 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

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 > 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

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 > 8 mg/L and AVI 50% fT > 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 > 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 < 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 < 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

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 >MIC). 50% fT >MIC was defined as Cm >MIC, and 100% fT >MIC was defined as Ct >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 >MIC was lower in the AD group, as compared to the SD group (CPZ: 15.4% versus 54.5%, P< 0.01; SUL: 11.5% versus 72.7%, P< 0.01). Additionally, 7.7% of patients in the AD group compared to 45.5% of patients in the SD group achieved 100% fT >MIC for both CPZ and SUL (P< 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

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
P-1313. Large Outbreak of Staphylococcus aureus and Bacillus cereus Caused by Ready-to-Eat Meals in Aomori, Japan
Authors: Eita Mizue , Yahata Yuichiro , Nakamura Natsuko , Fujita Keiichiro , Saito Masato , Matsukura Kaori , Takagi Hiromi , Nakamura Mizuki , Shimada Tomoe , Ishii Atsuko , Kudou Masanobu , Sunagawa Tomimasa
Published: January 2025

Background

Ready-to-eat meals are a vehicle of multijurisdictional outbreaks of foodborne diseases worldwide. Ekiben is a type of ready-to-eat meal commonly sold at train stations and occasionally at markets in Japan. On September 17, 2023, the Hachinohe City Public Health Center (HCPHC) received numerous complaints from consumers in several prefectures who had eaten ekiben produced by Company A in Hachinohe, Aomori, Japan.

Methods

In collaboration with HCPHC, we conducted an epidemiological investigation, traceback/traceforward investigation, and an inspection of Company A. The local public health authorities performed microbiological tests of food and stool samples.

Results

A total of 554 symptomatic cases were identified in 29 prefectures. The highest proportion of symptoms was diarrhea (86%), followed by vomiting (61%), nausea (59%), and stomachache (51%). Company A produced 67 lunchboxes of which 23 types of lunchboxes occurred cases. 23 lunchboxes contained seafood as an ingredient but no common ingredients except for rice. The rice was self-produced and/or outsourced from Company B. Company A received triple the number of usual orders from retailers and trading companies due to an “Ekiben Fair” held on September 15 and 16. Company A could not prepare enough steamed rice for such an event on its own, so it outsourced the production of some rice to Company B, which shipped the rice at temperatures ranging from 42°C–49°C. Staphylococcus aureus with enterotoxin and Bacillus cereus with enterotoxin were detected from stool samples as well as steamed rice and other food samples with sufficient amounts of bacteria to cause the disease. Company A did not have an appropriate HACCP plan, operation manual, response plan, or processing records. The company had no records of hygiene training, hygiene education, health checks, or hand-injury records for its temporary workers. We concluded that the likely causative food was steamed rice that had been shipped at an improper storage temperature, and processing the lunchboxes.

Conclusion

We recommended that Company A store rice at the proper temperature, implement an appropriate HACCP plan, create a standard operation manual, maintain processing records, separate clean and contaminated areas, and prepare a response plan in case of unusual situations.

Disclosures

All Authors: No reported disclosures
P-1320. HAISeq: Monitoring Emerging and Novel Gram-Negative Antimicrobial Threats from Healthcare Settings in the United States with Publicly Available NCBI BioProject Data
Authors: Moser Kara A , Kent Alyssa , Hagey Jill V , McAllister Gillian A , Aubert Rachael , Halpin Alison L
Published: January 2025

Background

Gram-negative healthcare-associated infections (HAIs) and antimicrobial resistance (AR) cause considerable morbidity and mortality in the United States. Whole genome sequencing (WGS) has become a critical methodology to describe HAIs, providing important contextual information on resistance genes and relatedness. It is essential that public health agencies leverage large amounts of WGS data quickly for public health action, and that data can be accessible across jurisdictions.

Methods

In advance of an influx of resources to state public health laboratories for HAI/AR WGS capacity, CDC’s Division of Healthcare Quality Promotion (DHQP) established the HAISeq Umbrella BioProject in the National Center for Biotechnology Information’s Short Read Archive as a centralized repository for WGS data generated by DHQP and partners. Data submitted is from CDC’s Antimicrobial Resistance Laboratory Network, surveillance projects, and outbreak investigations.

Results

The gram-negative-specific BioProject within the HAISeq Umbrella currently contains 6.5TB of WGS data, representing > 20,000 gram-negative isolates, ∼40 genera, and > 450 unique AR genes. While DHQP priorities are heavily reflected in represented genera (Acinetobacter, Pseudomonas, Klebsiella, Escherichia) and gene targets (e.g., >10 carbapenemase families), the dataset also represents hundreds of minor frequency species and genes captured from the above sequencing efforts. DHQP uses bimonthly data pulls to detect potential novel and emerging HAI/AR genetic threats. Examples include identification of novel carbapenemase variants (e.g., 23 variants from all “Big 5” groups), variants that convey unexpected phenotypes to treatment options (e.g., carbapenem susceptible but ceftazidime-avibactam resistant), and rare gene/organism combinations (e.g., blaOXA-48-like genes in Acinetobacter baumannii). Data are also used to rapidly provide feedback to public health laboratories on data quality issues. Finally, these data help inform national HAI/AR sequencing priorities.

Conclusion

This publicly available dataset, alone and in combination with traditional testing data, allows for both federal and state public health labs to leverage WGS for public health action while maintaining data privacy.

Disclosures

All Authors: No reported disclosures
P-1347. Characterizing Atypical Antibiotic Non-Susceptibility Features of Emergent U.S. Carbapenem-resistant Acinetobacter baumannii Lineages
Authors: Graffice Emma , Siam Md Hasanul Banna , Calix Juan , Amerson-Brown Megan
Published: January 2025

Background

Due to elevated genetic divergence between different Carbapenem-resistant (CR) A. baumannii (Ab) lineages, CRAb isolates belonging to clonal groups (CGs) currently emerging in the U.S. may display traits that differ from those of unrelated international CGs. Variations in CG-associated physiology could especially affect the choice and interpretation of antimicrobial susceptibility tests (AST) for these multidrug resistant lineages.

Methods

We integrated multimodal AST and comparative genomic analysis of CG108, CG406, and CG499 isolates identified in two U.S. cities since 2017. Lineage-specific resistance features were queried among genomes of isolates from other U.S. locations. We further investigated a unique sulfonamide (SXT) heteroresistance trait via mutational analysis.

Results

Most antibiotic non-susceptibility was attributable to conventional, lineage-independent resistance determinants on mobile genetic elements. In contrast, a FtsI A515V polymorphism shared among CG108 genomes appears to confer carbapenem resistance independent of carbapenamases, while genomes of various CG406 CRAb isolates lacked any readily identifiable CR determinant. We observed antibiotic-specific heteroresistance against sulbactam (SAM) and imipenem among CG108 isolates and against SXT among CG499 isolates. Integrity of the wzc gene in a CG499 isolate was necessary for high-molecular weight capsule polysaccharide (KPS) production and SXT heteroresistance. Despite lacking any conventional resistance determinants, the wzc-deficient mutant and all other CG499 isolates displayed greater resistance to SXT compared to most susceptible Ab isolates.

Conclusion

We describe AST features unique to emerging CRAb CGs and independent of conventional extrinsic resistance genes. CG499 SXT heteroresistance appears to rely on the ability to produce high-molecular weight KPS, though another unidentified mechanism also contributes to decreased susceptibility compared to wild-type. We propose ongoing surveillance efforts must recognize lineage-related variations to best tailor new strategies against the evolving nature of CRAb disease.

Disclosures

Megan Amerson-Brown, PhD, Selux diagnostics: Grant/Research Support
P-1351. Occurrence of b-lactamases among Enterobacterales isolates from United States Hospitals in a 10-year period: Report from the International Network for Optimal Resistance Monitoring (INFORM) Program
Authors: Castanheira Mariana , Doyle Timothy , Hubler Cory , Deshpande Lalitagauri , Mendes Rodrigo E , Sader Helio S
Published: January 2025

Background

β-lactamase-production in Enterobacterales challenge the use of β-lactams, the most broadly used and versatile class of antimicrobial agents. The INFORM program surveys β-lactamases and the activity of ceftazidime-avibactam in US hospitals. We analyzed 10 years of data from that study.

Yearly distribution of most common β-lactamases among E. coli (EC) and K. pneumoniae (KPN) isolates collected during 2013-2022 in US hospitals

Methods

90,956 Enterobacterales isolates were consecutively collected in 22 US hospitals participating in the INFORM program during 2013 to 2022. Susceptibility testing was performed and interpreted according to CLSI. E. coli (EC) and K. pneumoniae (KPN) displaying MICs ≥ 2 mg/L for two of: ceftriaxone, ceftazidime, cefepime or aztreonam; or carbapenem-resistant Enterobacterales (CRE; resistant to meropenem or imipenem) were evaluated for the presence of β-lactamase genes. Genetic analysis was performed by microarray/PCR (2013-2015) or whole genome sequencing (2016-2022).

Yearly distribution of CRE isolates collected during 2013-2022 in US hospitals

Results

ESBLs were detected among 2,334/2,691 (15.6% of 14,969 overall non-CRE isolates) EC and 964/1,051 (13.8% of 6,988) KPN. A decline in EC displaying the phenotypic criteria and CTX-M-15-like isolates (12.6% in 2021 and 8.3% overall in 2022; Figure 1) was noted in 2022. The most common ESBL in both groups was CTX-M-15-like (10.5/58.3% of the EC overall/characterized and 11.0/73.4% of the KPN). SHV ESBLs had a steady decline among KPN since 2015. CRE isolates declined steadily from 1.6% in 2013 to 0.8% in 2022 (Figure 2). Carbapenemase-positive isolates also declined from 1.3% to 0.6%, with a decline in KPC producers but an increase in isolates producing NDM that were initially detected in 2015 and range from 10-16 isolates in the last 3 study years. Ceftazidime-avibactam and the carbapenems are the most active agents against β-lactamase-producing isolates (Figure 3).

Activity of ceftazidime-avibactam and comparators against main β-lactamase groups

Conclusion

Changes in β-lactamase-producing isolates and its susceptibility profiles should be closely monitored in a local and global level since it impacts patient treatment, but longitudinal data such as this information is scarce.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
501. Impact of Implementation of World Health Organization (WHO) National Action Plans (NAP) on Antibiotic Rates: A Time Series Analysis of 38 Countries
Authors: Miner Tate , Callaway Kim Katherine , Rothenberger Scott , Chaudhry Shanzeh , Tadrous Mina , Suda Katie J
Published: January 2025

Background

Antimicrobial Resistance (AMR) poses a major threat to global health. In 2015, the World Health Organization (WHO) advised that member nations should develop National Action Plans (NAPs) to improve antibiotic stewardship and decrease AMR. However, the association between NAP implementation and antibiotic use is unknown. The objective of this study, therefore, was to examine post NAP-implementation changes in antibiotic utilization.Figure 1:Relative change in the population-based antibiotic rate after 2 years of implementation of National Action Plans (NAP)

Methods

We conducted a longitudinal repeated cross-sectional study of antibiotic purchases leveraging IQVIA’s MIDAS database. Our sample included 38 countries which implemented NAPs from June 2013 to January 2018. Quarterly purchases were reported in standardized units (1 pill/capsule/vial/5mL oral liquid) per 1 million population. We conducted an interrupted time-series analysis using mixed effects negative binomial models with a log link to assess level and trend changes in the antibiotic purchasing rate in the 8 quarters after each country’s NAP implementation, relative to 8 quarters pre-implementation. We included sinusoidal terms to account for seasonality, as well as random effects to estimate country-specific changes in rates after 8 quarters.

Results

Across all countries, the average level change post-NAP implementation was .03 log units (p=.44), and the average trend decreased by -.0014 log units per quarter (p=.72). After two years, the overall relative change in the purchasing rate was 1.9% [-7.8, 12.5], with country-specific effects ranging from -38.6% to 216% (See Figure 1). Only 4 countries (Norway, Jordan, South Africa, and Indonesia) experienced significant decreases.

Conclusion

Implementation of the NAP was not associated with overall changes in antibiotic purchasing two years later. The findings of this study may be useful for evaluating the effectiveness of these policies in terms of their stated objectives as well as identifying factors that led to the success of those countries that did observe decreases in antibiotic utilization.

Disclosures

All Authors: No reported disclosures
P-1361. Cefiderocol Activity against Pseudomonas aeruginosa, Including Resistant Subsets and Isolates Carrying Carbapenemase β-lactamase Genes, from United States Hospitals (2020–2023)
Authors: Mendes Rodrigo E , Maher Joshua , Hubler Cory , Scullin Abigail , Karr Maura , Kimbrough Hank , Castanheira Mariana
Published: January 2025

Background

Pseudomonas aeruginosa (PSA) possess various intrinsic treatment-limiting resistance mechanisms, leading to decreased antibiotic permeability, and also the ability to acquire resistance. Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. The activity of FDC and comparator agents were evaluated against PSA causing infections in US hospitals, including resistant subsets, as part of the SENTRY Antimicrobial Surveillance Program.

Methods

4,400 PSA were collected from 36 sites in the US in 2020–2023. Susceptibility (S) testing was performed by broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI/FDA criteria were applied. Isolates with imipenem (IMI) or meropenem MIC ≥4 mg/L (nonS by CLSI) were screened for β-lactamase genes. Multidrug resistance (MDR) was defined as nonS to ≥3 drug classes by CLSI; whereas, extensively drug resistance (XDR) was defined as nonS to all but 2 or fewer drug classes.

Results

14.6% (643/4,400) and 4.7% (206/4,400) PSA isolates were MDR and XDR, respectively. 22.3% (980/4,400) PSA were carbapenem-nonS, with only 9 (0.9%) strains carrying carbapenemases. FDC and β-lactam/β-lactamase inhibitor (BL/BLI) combinations showed S of > 95% against all PSA, except for piperacilin-tazobactam (79.9%S) (Table). FDC (90.8–99.4%) showed MIC50 of 0.12 mg/L and MIC90 of 0.5–1 mg/L against MDR, XDR and carbapenem-nonS isolates, whereas BL/BLI showed S of 2.9–90.2%. FDC (100%S) inhibited all PSA carrying carbapenemases at the CLSI S breakpoint of ≤2 mg/L. Other comparators showed S of < 35% against the latter subset. FDC (MIC50/90, 0.12/0.5 mg/L; 96.8–99.4%S) had MIC 4- to 8-fold lower than IMI-relebactam (MIC50/90, 1/2 mg/L; 90.0%S) and cetolozane-tazobactam (MIC50/90, 1/4 mg/L; 90.9%S), which were also active against carbapenem-nonS PSA absent of carbapenemase genes.

Conclusion

FDC showed potent and cosistent activity against PSA clinical isolates from US hospitals, including resistant subsets and those with or without carbapenemase genes. These data demonstrate FDC activity against PSA resistant subsets, for which antibiotic treatment options are limited.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1362. Cefiderocol Activity against Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex, Including Molecularly Characterized Clinical Isolates, Causing Infections in United States Hospitals (2020–2023)
Authors: Mendes Rodrigo E , Scullin Abigail , Kimbrough Hank , Karr Maura , Maher Joshua , Hubler Cory , Castanheira Mariana
Published: January 2025

Background

Multidrug-resistant (MDR) Acinetobacter baumannii-calcoaceticus complex (ACB) have gained attention as an important clinical challenge in the last decades, due to its ability to develop resistance to front-line antibiotics. Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. The activity of FDC and comparators were evaluated against ACB causing infections in US hospitals, including resistant subsets, collected as part of the SENTRY Antimicrobial Surveillance Program.

Methods

1,786 Acinetobacter spp. were collected from 36 sites in the US during 2020–2023. Susceptibility (S) testing was performed by broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI/EUCAST/FDA criteria were applied. Isolates with imipenem or meropenem MIC ≥4 mg/L (nonS by CLSI) were screened for β-lactamase genes.

Results

ACB comprised 80.5% (1,438/1,786) of isolates collected, and all 405 carbapenem-nonS isolates were identified as ACB. Carbapenemase genes were detected in 86.9% (352/405) of carbapenem-nonS ACB, and blaOXA-23 (59.9%; 211/352) prevailed, followed by blaOXA-24 (25.6%; 90/352), and blaOXA-72 (9.4%; 33/352). FDC (93.6–98.8%S) had MIC50 of 0.12 mg/L and MIC90 of 1 mg/L against all Acinetobacter spp. and the ACB subset (Table). Comparators had limited activity against these isolates (66.5–77.1%S), except for colistin (COL) (95.7–96.2%S). FDC (97.0–97.7%S by CLSI) had MIC50 of 0.25 mg/L and MIC90 of 2 mg/L against carbapenem-nonS ACB and those carrying carbapenemases. Only COL was also active against these 2 resistant subsets. FDC (97.2–100%S by CLSI) MIC90 of 2 mg/L, 1 mg/L and 0.5 mg/L were obtained against ACB carrying blaOXA-23, blaOXA-24, and blaOXA-72, respectively. Isolates carrying other carbapenemases were inhibited by FDC MIC of ≤2 mg/L, except for 1 strain with blaOXA-23 and blaNDM-1 (MIC, 8 mg/L).

Conclusion

This study demonstrates the MDR nature of ACB causing infections in US hospitals, and FDC as an active agent against these isolates, regardless of resistance genotype. These in vitro data suggest FDC as an important option for the treatment of infections caused by MDR ACB.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1417. High Rates of Patient Directed Discharge Associated with Incomplete Treatment and Rehospitalization in People Hospitalized with Serious Injection Related Infections: The CHOICE+ Cohort
Authors: Rosenthal Elana S , Kattakuzhy Sarah , Omari Habib , Stevens Jasmine , Derenoncourt Meghan , Vaish Ishan Kumar , Flores Hannah E , Fujita Ayako Wendy , Raman Sumitha , Steck Alaina , Kuo Irene , Catalanotti Jillian S , Carpenter Joseph E , Reece Becky , Traver Edward C
Published: January 2025

Background

People who inject drugs have high rates of patient directed discharge (PDD). In a cohort of patients hospitalized for serious injection related infections (SIRI), we aimed to assess the factors leading to PDD and the influence of PDD on rehospitalization.

Characteristics of study participants

Methods

CHOICE+ is a multisite retrospective cohort study of adults hospitalized at four healthcare systems with SIRI due to injection opioid use between 1/1/2018 and 3/31/2022. Data were collected by abstraction of the electronic medical record and were analyzed by chi-square and multivariable logistic and linear regression.

Factors associated with patient directed discharge

Results

Of 1645 patients, 1180 (72%) had a planned discharge and 465 (28%) had a PDD. PDD was associated with younger age (p< 0.001), white race (p=0.018), and documented opioid withdrawal (p< 0.001). PDD was less likely in patients on medication for opioid use disorder (MOUD) during hospitalization (p< 0.001) or who received consultations by infectious diseases (p< 0.001), social work (p=0.04), or addiction medicine (p=0.003).

Compared to those with planned discharge, patients with PDD were less likely to have completed antibiotics at the time of discharge (7% vs 60%; p< 0.001), and 64% left without a plan for antibiotic completion. Patients with PDD were more likely to be readmitted within a year (57% vs 52%; p=0.015), and more likely to have a first readmission due to an infection (81% vs 56%; p< 0.001). Time to readmission was significantly shorter among patients with PDD (15 vs 65d; -41.5 days, p< 0.001).

Post-Hospitalization Antibiotic Plan by Discharge Status

Conclusion

Among people hospitalized with SIRI, we found high rates of PDD associated with insufficient treatment of OUD, evidenced by withdrawal, lack of MOUD, and not receiving an addiction consultation. PDD was consequently associated with higher rates of readmission due to infection and shorter time to readmission, possibly due to discharge without a plan to complete antibiotics. To improve outcomes and reduce readmissions among people with SIRI, efforts to address OUD during hospitalization are crucial, and could reduce PDD. Regardless, given high rates of PDD in this population, strategies to facilitate continuity of antibiotics - including contingency plans for oral or long-acting regimens - may be critical to ensuring resolution of SIRI and improving long-term outcomes.

Risk of Readmission within 1-Year Based on Discharge Status

Disclosures

Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support