bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1232. PK/PD Analysis and Dose Optimization of Tebipenem and Faropenem against ESBL-Producing Enterobacterales in Patients with UTI Considering Renal Function
Authors: Hamada Yukihiro , Maruyama Takumi , Kasai Hidefumi , Yagi Yusuke , Matsunaga Nobuaki 
Published: January 2025

Abstract

Background
Tebipenem (TBPM) and faropenem (FRPM) have been proposed as effective treatments for urinary tract infections caused by ESBL-producing Enterobacterales. However, appropriate dosage according to renal function needs to be considered. This study utilized PK/PD analysis to investigate the optimal dosage.

Methods
Monte Carlo simulation using the model of Nakashima et al, 2009 for TBPM and Hirooka et al. 2005, for FRPM generated blood concentration profiles for 1000 cases stratified by renal function. The optimal dose metric was defined as the Probability of Target Attainment (PTA) of 90 percent or more for PK/PD parameters at the MIC90. The PK/PD parameters for TBPM and FRPM were defined as 24h free AUC/MIC/dosing interval 34.58 or more, and free time above MIC 20 and 40 percent or more. The MIC90 values were set at 0.03 and 2 mg/L, respectively.

Results
For TBPM, the dose achieving PTA of 90 percent or more was 150 mg (q12h) for creatinine clearance (Ccr) less than 30 and 300 mg (q8h) for Ccr 30 or more and less than 80 mL/min. For Ccr 80 mL/min or more was not achieved. None of the doses for FRPM achieved PTA of 90 percent or more.

Conclusion
The dose for TBPM suggested the need for an even higher dose for Ccr 80 mL/min or more. Cases of post-treatment relapse have been reported for FRPM. Therefore, the optimal dosage considering PK/PD analysis with urinary concentrations needs further validation.

Disclosures
All Authors: No reported disclosures
431. Engraftment of donor derived anaerobic taxa and durable long-term multidrug resistant organism decolonization following fecal microbiota transplantation
Authors: Babiker Ahmed , Brink Catherine , Lohsen Sarah , Van Riel Julia , Strudwick Amanda F , Kraft Colleen S , Satola Sarah W , Konstantinidis Kostas , Woodworth Michael H 
Published: January 2025

Abstract

Background
Microbiome restoration through fecal microbiota transplantation (FMT) is a promising decolonization approach that leads to reduction in multidrug resistant organism (MDRO) colonization and infections. The precise mechanisms by which FMT reduces MDRO colonization are not well elucidated, and long-term follow up (LTF) data from patients treated with FMT for MDRO decolonization are lacking. We enrolled participants of a recently conducted trial of FMT for MDRO decolonization (PREMIX, NCT02922816) to a LTF study to estimate long-term engraftment dynamics of donor derived anaerobic taxa and their association with MDRO decolonization.

Methods
Participants provided stool every 6 months for up to 5 years. Stool underwent selective culturing for MDROs by plating on selective chromogenic agars, and confirmation by MALDI-TOF and vitek2. MDROs underwent whole genome sequencing (WGS), and stool samples underwent metagenomic sequencing (mNGS). WGS resolved mNGS tracking of MDROs and metagenome-assembled genomes (MAG) of donor anaerobic taxa was performed. Pairwise comparison of baseline and long-term follow up (LTF) MDRO isolates was performed with a unique strain defined as 99.95% average nucleotide identify difference.

Results
Six PREMIX participants were enrolled to the LTF study, five of whom received FMT and one control. 80% (4/5) of FMT treated patients have remained decolonized (culture negative) while 0% (1/1) of control patients have remained decolonized at most recent follow up (median[IQR] 3.6 [3.4,4.0] years). For the FMT treated patient who had an MDRO detected on LTF sample, the MDRO represented a new acquisition (after broad-spectrum antibiotic exposure close to time of FMT), while the MDRO detected in LFT sample of the control patient was the same MDRO detected at baseline. mNGS revealed persistence of donor anaerobic strains in LTF samples (Agathobaclulum ammoniilyticum, Akermanisa muciniphila, Alistipes putredinis, Bacteroides uniformis, Barnesiella intestinihominis, Eubacterium xylanophilum, Gemmer formicilis), indicative of engraftment and persistence.

Conclusion
FMT was associated with long-term durable decolonization potentially mediated by the engraftment and persistence of donor derived anaerobic strains.

Disclosures
Ahmed Babiker, MBBS, Beckman Coulter Inc.: Advisor/Consultant Colleen S. Kraft, MD, MSc, Ferring/Rebiotix: Advisor/Consultant|Seres LLC: Advisor/Consultant
P-1289. Trends, Treatments, and Outcomes in Vibrio Species Infections: The UTMB Galveston Experience
Authors: Torres Grant Bradley , Brondeel Kimberley C , Cummins Andi J , Mesa Camila Franco , Klinnert Joshua , Branski Ludwik , Hornak Joseph Patrik , Cabada Miguel M , Reynoso David 
Published: January 2025

Abstract

Background
V. vulnificus, V. parahaemolyticus, and other species thrive in coastal water of areas such as the East Coast of Texas. There are few large-scale, single-institution retrospective studies investigating Vibrio spp. infections. Our study aims to determine the clinical presentation, management, and outcomes of infections caused by Vibrio spp. treated at the University of Texas Medical Branch (UTMB) in Galveston.

Methods
A retrospective chart review was conducted for patients with culture-positive Vibrio spp. samples at the UTMB from 2016-2023. Primary outcomes include clinical characteristics, antibiotic treatment, surgical management, and outcomes of Vibrio spp. infections. Secondary outcomes include demographic data, comorbidities, and causative agents for Vibrio spp. infections. This study was performed in collaboration with the infectious disease department and plastic surgery division at UTMB.

Results
25 patients treated for Vibrio-related infections were included. Patient demographic data is as follows: 24 (96%) were Caucasian, 23 (92%) were non-Hispanic, 21 (84%) were male, and the average age was 62.2 years. Nearly all cases occurred in Galveston County and the surrounding area, with 18 (72%) associated with water/aquatic exposure. 13 (52%) patients noted contact with marine life shortly before admission, comprising most of the 12 (48%) patients noting underlying injury before symptom onset. 8 patients had localized soft tissue infections, while 17 developed systemic infections. Most systemic manifestations developed secondary to soft tissue infection. Surgical intervention was required in nearly half of the patients. V. vulnificus was noted in 18 patients (mostly systemic), and V. parahaemolyticus was noted in 7 patients. The most common empiric antibiotics were Vancomycin, Piperacillin-Tazobactam, and Doxycycline—followed by Ceftriaxone, and Clindamycin.

Conclusion
In areas along the coast with warm seawater or brackish water, infections due to Virbio spp. warrant hefty consideration and prompt treatment—as over 2/3 of our patients quickly developed systemic infection and nearly half required surgical intervention. This is especially true for patients with open wounds exposed to these aquatic environments, and those in contact with marine life.

Disclosures
Joseph Patrik Hornak, MD, Innoviva Specialty Therapeutics: Advisor/Consultant|Innoviva Specialty Therapeutics: Advisor/Consultant
P-1291. Racial disparities in Lyme disease among beneficiaries of US Medicaid and Medicare
Authors: Hannah Gould L , Willis Sarah J , Prener Christopher G , Duench Stephanie A , Yu Holly , Moisi Jennifer , Stark James H 
Published: January 2025

Abstract

Background
Lyme disease (LD) is the most common vector-borne disease in the US. Manifestations range from a localized rash to neurologic, cardiac, and musculoskeletal conditions during disseminated stages. LD incidence is highest among White persons in the US, but evidence suggests that people from racial and ethnic minority groups experience more severe disease.

Methods
We used a claims-based algorithm (≥ 1 LD ICD-10 code and appropriate antibiotics within 30 days) to identify LD cases among Medicaid (age &lt; 19 and ≥ 19 years) and Medicare fee-for-service (age &lt; 65 [persons with disabilities] and ≥ 65 years old) beneficiaries living in 16 high incidence states ( &gt; 10 cases/100,000 population for ≥ 3 years) during 2016-2021. We calculated prevalence ratios for disseminated disease and hospitalization by racial group using White persons as the reference.

Results
There were 62,055 LD cases identified among Medicaid beneficiaries and 90,882 among Medicare beneficiaries. In Medicaid, 85% of cases were in White persons, 6% in Hispanic, 4% in Black, 4% in Asian/Pacific Islander, and 1% in Native American persons. In Medicare, 96% of cases were in White persons, with 1% or less reported in other groups. Non-White persons were more likely to be hospitalized at diagnosis, diagnosed outside of primary care, diagnosed outside of the peak months for LD transmission, to be female, and to have disseminated disease (Table 1). Medicaid beneficiaries and Medicare beneficiaries ≥ 65 years old who identified as Black, Asian/Pacific Islander, or Hispanic had a higher likelihood of disseminated disease than White persons. Among Medicaid beneficiaries &lt; 19 years old, those who identified as Black, Asian/Pacific Islander, or Hispanic had a higher likelihood of being hospitalized at diagnosis than those who identified as White. Black Medicaid beneficiaries ≥ 19 and Medicare beneficiaries &lt; 65 also had a higher likelihood of hospitalization (Table 2).

Conclusion
These data illustrate disparities in LD by race and ethnicity and suggest possible disparities by other characteristics including sex and, given the high rates of disseminated disease in Medicare beneficiaries &lt; 65 years old, disability. Equitable interventions are needed to reduce disparities in LD recognition and severity.

Disclosures
L. Hannah Gould, PhD, MS, MBA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Sarah J. Willis, PhD, MPH, Pfizer, Inc.: Employment|Pfizer, Inc.: Stocks/Bonds (Private Company) Christopher G. Prener, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Stephanie A. Duench, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Holly Yu, MSPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Jennifer Moisi, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-1311. Infectious diseases trends in migrant populations at a safety-net community hospital in Chicago
Authors: Khan Mashaal , Vergara-Mojica Stephanie , Zodo Alexandra , Ali Mirza , Mena Lora Alfredo J 
Published: January 2025

Abstract

Background
Chicago's recent increase in migrant populations has placed new demands on public health systems, particularly in managing infectious diseases within community hospitals. This study examines the impact of migration on the incidence of infectious diseases in a community hospital's emergency department (ED). Understanding disease patterns in migrants can inform public health strategies and improve healthcare delivery.
Figure 1. Chickenpox and measles cases per year

Methods
We conducted a retrospective review of infection prevention records from a 151-bed Chicago safety-net community hospital was conducted, focusing on migrant patient visits and infection prevention needs between 2022 and 2024. Descriptive statistics were used to evaluate the changes over the period.
Figure 2. Infectious diseases cases in migrant populations per month

Results
In 2022, 2023 and 2024, the reported cases of chickenpox rose from 0 to 5 and then 11, respectively. This represents a 450% increase in chickenpox cases from 2023 to 2024 (Figure 1). No measles cases were reported in the first two years, increasing to 2 cases in 2024. From October 2023 to March 2024, a total 18 chickenpox cases, 2 measles cases and two cases of tuberculosis were reported (Figure 2). Airborne precautions in the ED were needed for 22 cases.

Conclusion
We report a notable increase in vaccine preventable conditions such as chickenpox and measles in a Chicago hospital associated with a migrant influx. Added needs for airborne precautions in the ED were required during this period. These trends highlight the need for public health measures, such as enhanced vaccination efforts and healthcare access for migrants, to prevent disease outbreaks and protect community health. Infection prevention readiness should involve clear protocols for identifying and isolating conditions requiring airborne precautions.

Disclosures
All Authors: No reported disclosures
P-1344. Molecular Characterization of Daptomycin Non-susceptible Staphylococcus aureus
Authors: Suleyman Geehan , Kaur Jagjeet , Zhang Xiangmin , Tibbetts Robert , Zervos Marcus , Alangaden George J 
Published: January 2025

Abstract

Background
Staphylococcus aureus (SA) is the leading cause of bacteremia in hospitalized patients. With limited therapeutic options, increasing use of daptomycin (DAP) has resulted in the emergence of DAP non-susceptible (DNS) SA strains. Nevertheless, the mechanisms of resistance in DNS SA are not fully understood. Proposed mechanisms include genetic and phenotypic changes affecting the cell membrane and cell wall. However, studies have been limited to single pairs of isolates or isolates that are laboratory derived.

Methods
We performed whole-genome sequencing (WGS) on clinically obtained SA blood isolates at Henry Ford Health, a comprehensive, integrated, health care organization in Southeast Michigan from 2005-2023. DNS was defined as MIC &gt;1. Sequencing libraries were created using QIAseq FX DNA Library Kit (Qiagen, USA) according to manufacturer’s instructions and sequenced on NovaSeq 6000 (Illumina, San Diego, USA). FastQ files were further analyzed for the presence of genetic variations using a WGS bioinformatic pipeline based on de novo assembly.

Results
We sequenced 199 SA isolates from 59 patients, of which 88 (44%) were DNS. 43 (73%) patients had multiple isolates, whereas 16 (27%) only had one. All DNS isolates except one were MRSA. 46 (52%) DNS isolates had amino acid substitution in the MprF and 2 (2%) in the cls genes, which are known to be associated with DNS. 10 (11%) DNS isolates were found to have substitutions (S829L and L406I) in the MprF gene that have not been previously reported. Mutations in cls, rpoB, rpoC, walK and agrA genes were also detected. All isolates with known mutations were exposed to DAP prior to development of DNS. 30 (34%) DNS isolates did not have mutations associated with resistance. Of these, only 13 (43%) had prior exposure to DAP, 9 (30%) were only exposed to vancomycin, and 11 (37%) were not exposed to any antibiotics. ST5 and ST8 were the most common sequence types.

Conclusion
In this study involving a large number of clinical SA isolates, the majority of patients who developed DNS due to MprF mutations were exposed to DAP, likely due to selection pressure. However, more than one-third of DNS isolates did not exhibit resistance mutations. Further studies are needed to identify other mechanisms of DAP resistance, especially in those with no prior antibiotic exposure.

Disclosures
Marcus Zervos, MD, Johnson and johnson: Grant/Research Support|Moderna: Grant/Research Support
P-1348. Acquired Carbapenemase-Producing Gram-Negative Organisms (CPOs) Across the Pond: Surveillance of Antibiotic Resistance in CPOs in England from 2020-2023
Authors: Henderson Katherine L , Guy Rebecca L , McCormick Jacquelyn , Patel Bharat , Jeyaratnam Dakshika , Mirfenderesky Mariyam , Hopkins Katie L , Hope Russell 
Published: January 2025

Abstract

Background
Acquired carbapenemase-producing Gram-negative organisms (CPOs) threaten viable antibiotic treatment options. This is the first national look at CPO phenotypic antimicrobial resistance (AMR) rates since becoming statutorily notifiable in England on 01/10/2020.Table 1.Summary of all big-5 CPO isolates reported from October 2020 to December 2023

Methods
All acquired big-5 (NDM, KPC, OXA-48-like, VIM, IMP) CPO reported specimens and antibiotic susceptibilities were extracted from national laboratory surveillance databases between Oct-2020 to Dec-2023. Records were deduplicated by patient, specimen group (invasive/screening/other), bacterial species and CPO mechanism per year. Regional big-5 CPO population rates were calculated; 2023 AMR data were assessed by mechanism and species.Figure 1.Regional notifications per 100,000 population of acquired CPOs by big-5 carbapenemase mechanisms in England, 2023

Results
In total, 13,022 episodes from 9,945 patients were reported; median age was 70y, 54% were male. The dominant mechanisms were OXA-48-like (n=4,884; 37.6%), NDM (n=3,927; 30.2%) and KPC (n=3,045; 23.4%); (Table 1) with large regional variation (Figure 1). NDMs became more dominant in 2023 than OXA-48-like. Screening samples accounted for 72% (n=9,378), and &lt; 5% (n=591) were from invasive samples. Thirty-three patients with invasive samples had dual-mechanisms detected: 61% were NDM & OXA-48-like; Klebsiella pneumoniae was the dominant species (patients=21).
In 2023, the lowest reported resistance for the most frequently isolated species (n=5,535/5,711; Table 2) was for colistin (4-7%R) for all big-5 mechanisms in Escherichia coli, Enterobacter spp., Citrobacter spp., whilst higher for Klebsiella spp. and Pseudomonas spp. (10-17%R). Similarly, lower Enterobacterales resistance was observed for KPC and OXA-48-like to ceftazidime/avibactam (9-12%R) and amikacin (7-8%R), except for Klebsiella spp., which was higher (22%R). Ciprofloxacin and gentamicin had ≥ 35% resistance. Fosfomycin resistance in E. coli was low (≤ 9%).
Proportion of big-5 CPO isolates (n=5,535) resistant to other antimicrobials by most frequently isolates species in England, 2023

Conclusion
Continued national CPO and associated AMR surveillance is crucial, particularly for new antimicrobials, to inform guidance and local, empiric prescribing by region, given the geographical variation in CPO mechanism. Further enhancement via data linkage to ethnicity and clinical characteristics to identify risk factors, and tracking changes in patients’ antibiograms over time would help further target national guidance.

Disclosures
All Authors: No reported disclosures
502. Epidemiology and Outcomes of Broad-Spectrum Antibiotic De-escalation in Patients with Suspected Sepsis in US Hospitals
Authors: Kam Kai-Qian , Chen Tom , Kadri Sameer S , Lawandi Alexander , Yek Christina , Walker Morgan , Warner Sarah , Fram David , Chen Huai-Chun , Shappell Claire N , DelloStritto Laura , Jin Robert , Klompas Michael , Rhee Chanu 
Published: January 2025

Abstract

Background
Guidelines recommend de-escalation of broad-spectrum antibiotics initiated for suspected sepsis based on clinical status and microbiological results after 48-72 hours, yet real world patterns of de-escalation remain unknown. We aimed to evaluate the frequency, hospital-level variation, predictors, and clinical outcomes of antibiotic de-escalation in suspected sepsis.

Methods
We used the PINC AITM Healthcare Database to retrospectively analyze adults admitted to 236 US hospitals between 2017-2021 with suspected sepsis (blood culture and lactate drawn) and minimal 4-day stay who received ≥2 days of empiric anti-MRSA and anti-pseudomonal antibiotics on admission, in the absence of any beta-lactam resistant gram-positive or ceftriaxone-resistant gram-negative organisms in the clinical cultures by day 4.De-escalation was defined as cessation or switching to narrower spectrum intravenous or oral agents by day 4. We utilized a multivariate logistic regression model with 82 covariates to predict the likelihood of de-escalation; the probabilities from this model were then used for propensity-score matching.

Results
Among 124,577 patients who met inclusion criteria, 36,806 (29.5%) had antibiotics de-escalated (21.8% narrowed, 7.7% stopped) (Figure 1). The median hospital-level de-escalation rate was 29.4% (IQR: 21.3-38.0%) and varied across hospital types (Figure 2). Predictors of de-escalation included clinical indicators of less severe disease (especially on days 3-4), positive cultures, and negative/absent MRSA nasal swabs (Figure 3). De-escalation was also associated with medium, large or teaching hospitals in the Northeast or Midwest region. On propensity-matched analysis (effective sample size of 32,964 and 36,803 in control and treated groups, respectively), de-escalation was associated with lower rates of acute kidney injury (OR 0.91, 95% CI 0.85-0.96), inpatient mortality (OR 0.89, 95% CI 0.83-0.96), and a trend towards fewer C.difficile infections (OR 0.84, 95% CI 0.71-1.01) (Table 1).

Conclusion
In this large US cohort, antibiotic de-escalation in patients with suspected sepsis was infrequent and variable across hospitals. De-escalation was influenced by clinical and microbiologic factors and associated with lower risk for adverse outcomes.

Disclosures
Michael Klompas, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|UpToDate: Royalties
P-1384. Rates of Follow-Up Testing for Chlamydia trachomatis and Neisseria gonorrhoeae Among Active-Duty Service Members
Authors: Marsh James J , Aleman-Reyes David Manuel , Marcus Joseph 
Published: January 2025

Abstract

Background
All patients who test positive for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) should get retested at three months to evaluate for re-infection. The United States military has previously been reported to have high rates of CT and GC, but follow-up rates have not been established for active-duty service members (ADSM) who test positive for CT or GC. This study evaluates factors associated with follow-up CT or GC testing in ADSM.

Methods
Positive cases of CT and GC among ADSM who were stationed at Joint Base San Antonio between January and June 2023 were evaluated. Demographic characteristics, location of testing, and the presence of symptoms were described. A patient was determined to have had follow-up testing if they had a repeat CT/GC test within 3-12 months after their initial positive test. Follow-up rates were compared among groups based on demographics, clinical setting of testing, and presence of symptoms using chi-square or Fisher’s exact test.

Results
Of the 200 ADSM who tested positive for CT or GC during the study period, 101 (51%) were male and the median age was 23 [IQR: 20-26] (Table 1). Women were significantly more likely to receive follow-up testing as compared to men (71% vs. 51%; p=0.003), without significant difference in follow-up testing by clinic, race, service, or original STI organism (Table 2). Women who were symptomatic at time of initial test were significantly more likely than symptomatic men to have a follow-up test (76% vs. 49%; p=0.003), but this difference did not hold for asymptomatic patients (64% vs. 53%, p=0.28) (Table 3).

Conclusion
Despite standardized follow-up testing recommendations, there were significantly lower follow-up testing rates in men, with the greatest difference in testing in patients who were symptomatic at presentation. While ADSM have universal access to care, the difference in follow-up testing between men and women based on presence of symptoms reinforces concerns about stigma in obtaining treatment and follow-up. Future work should study how standardization of guidelines in these populations promotes improvement in follow-up testing.

Disclosures
All Authors: No reported disclosures