bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial disparities in hospitalization and neighborhood deprivation among Medicare beneficiaries
Authors: Poghosyan Lusine , Liu Jianfang , Chen Julius L , Flandrick Kathleen , McMenamin Amy , Porat-Dahlerbruch Joshua , Rowell-Cunsolo Tawandra L , Martsolf Grant R
Published: January 2025

Many neighborhoods with concentrated racial and ethnic minority older adult populations experience high neighborhood disadvantage. Yet, to date, no studies have analyzed how neighborhood disadvantage affects the relationship between race and hospitalization among older adults. To fill this gap, we examined if neighborhood disadvantage moderates the relationship between race and hospitalization among older adults in the United States. Medicare claims data from 2018 on 530 962 beneficiary hospitalizations were merged with neighborhood data, and regression models assessed if the Area Deprivation Index (ADI) moderated the association between race and hospitalization. At the highest ADI score, the odds ratio (OR) for hospitalization for Black compared with White beneficiaries was the lowest (OR: 0.96; 95% CI: 0.89-1.04). At the lowest ADI score, the OR for hospitalization for Black compared with White beneficiaries was the highest (OR: 1.19; 95% CI: 1.09-1.29). When Black and White beneficiaries reside in severely deprived areas, the disparity in their outcomes is narrower. However, when they reside in areas with more advantages, White beneficiaries experience better outcomes than Black beneficiaries. Our findings have implications for practice and policy to invest resources in communities to assure health equity.
Telomere-to-telomere gap-free genome assembly provides genetic insight into the triterpenoid saponins biosynthesis in Platycodon grandiflorus
Authors: Yu Hanwen , Wang Haixia , Liang Xiao , Liu Juan , Jiang Chao , Chi Xiulian , Zhi Nannan , Su Ping , Zha Liangping , Gui Shuangying
Published: January 2025

Platycodon grandiflorus has been widely used in Asia as a medicinal herb and food because of its anti-inflammatory and hepatoprotective properties. P. grandiflorus has important clinical value because of the active triterpenoid saponins in its roots. However, the biosynthetic pathway of triterpenoid saponins in P. grandiflorus remains unclear, and the related genes remain unknown. Therefore, in this study, we assembled a high-quality and integrated telomere-to-telomere P. grandiflorus reference genome and combined time-specific transcriptome and metabolome profiling to identify the cytochrome P450s (CYPs) responsible for the hydroxylation processes involved in triterpenoid saponin biosynthesis. Nine chromosomes were assembled without gaps or mismatches, and nine centromeres and 18 telomere regions were identified. This genome eliminated redundant sequences from previous genome versions and incorporated structural variation information. Comparative analysis of the P. grandiflorus genome revealed that P. grandiflorus underwent a core eudicot γ-WGT event. We screened 211 CYPs and found that tandem and proximal duplications may be crucial for the expansion of CYP families. We outlined the proposed hydroxylation steps, likely catalyzed by the CYP716A/72A/749A families, in platycodin biosynthesis and identified three PgCYP716A, seven PgCYP72A, and seven PgCYP749A genes that showed a positive correlation with platycodin biosynthesis. By establishing a T2T assembly genome, transcriptome, and metabolome resource for P. grandiflorus, provides a foundation for the complete elucidation of the platycodins biosynthetic pathway, consequently leading to heterologous bioproduction, and a fundamental genetic resource for molecular-assisted breeding and genetic improvement of P. grandiflorus.
Community-based HbA1c testing programme for early detection of undiagnosed diabetes in community pharmacy
Authors: Shono Aiko , Morihiro Aki , Harada Nobue , Seposo Xerxes , Mimura Wataru , Hoshi Shu-ling , Yahagi Naoya , Miyazaki Seiko , Kondo Masahide
Published: January 2025

Objective

Testing with fingertip blood sampling, including HbA1c testing, has been available in community pharmacies in Japan since 2014. In 2016, the Mihara Pharmacy Association in Hiroshima Prefecture, in collaboration with the Mihara municipal government, developed a community programme that utilized the walk-in HbA1c test that could be offered by participating community pharmacies. The aim of this study was to assess whether the new programme could detect undiagnosed DM in the community and to compare groups who had and had not accessed the SHCG programme among SHCG eligible participants.

Method

The programme includes pharmacist advice following participants conducted Hba1c testing in the pharmacy, and completing a questionnaire to collect self-reported personal data including lifestyle, demography, height, weight, and blood pressure. All those accessing the programme were included. We analysed data from fiscal years 2016 to 2018, obtained retrospectively from the questionnaires.

Key findings

The participants aged 40–74 years who were the target of a national health check programme represented 73.7% of the 1933 total unique participants. Approximately 40% of these participants did not undergo routine checkups, 23.8% had HbA1c scores ≥5.6%, and 2.7% had HbA1c scores ≥6.5%.

Conclusions

The walk-in HbA1c community testing programme provided an opportunity to test the diabetes mellitus risk of residents, especially those who have missed their routine checkups. If the community programme were adopted widely, more undiagnosed populations at risk for diabetes mellitus could be detected in the early stages and the use of community resources such as pharmacists and pharmacies would be utilized.
Prevalence of antifungal allergies in the general population
Authors: Shiferaw Meron W , Donnelley Monica A , Thompson George R
Published: January 2025

Objectives

Invasive fungal infections are increasing in frequency and are associated with high patient morbidity and mortality. The use of antifungal therapy is thus also increasing, and patients reporting hypersensitivity or allergic reactions to the limited antifungal agents currently available complicates management. There are no prior studies defining the incidence of antifungal allergies reported by patients.

Methods

A multicentre retrospective cohort review of all patient encounters at five large academic centres during 2023 was conducted. The primary outcome of this study was to find the prevalence of reported antifungal allergy across the University of California Health System, and secondarily determine the incidence of antifungal allergies among patients with documented administration of antifungal agent.

Results

A total of 1 704 176 patients were included and 2602 patients exhibited a documented antifungal allergy. Prevalences of antifungal allergies were: fluconazole 1591 (0.093%), general antifungal allergy 395 (0.023%), triazole 361 (0.021%), itraconazole 145 (0.008%), amphotericin 110 (0.006%) and flucytosine <10 (0.001%). In the secondary outcome (incidence), 9829 patients received an antifungal agent and 298 reported an antifungal allergy (2.98%).

Conclusions

Increasing age and use of antifungal therapy are associated with antifungal allergy prevalence. Antifungal allergy rates (prevalence and incidence) are also comparable to the rates reported for antibacterial agents and are highest with fluconazole.
Humic substances modulate bacterial communities and mitigate adverse effects of temperature stress in coral reef organisms
Authors: Stuij T M , Cleary D F R , de Voogd N J , Rocha R J M , Polonia A R M , Silva D A M , Frommlet J C , Louvado A , Huang Y M , Gomes N C M
Published: January 2025

Aims

In the present study, we tested if terrestrially-derived humic substances (HS) could mitigate the adverse effects of elevated temperature and UVB radiation on the bacterial communities of two hard corals (Montipora digitata and Montipora capricornis), one soft coral (Sarcophyton glaucum), sediment and water. We also examined the impact of temperature, UVB radiation and HS supplementation on coral photosynthetic activity, a proxy for coral bleaching.

Methods and results

We performed a multifactorial experiment using a randomized-controlled microcosm setup. Coral photosynthetic efficiency was measured in vivo using a pulse amplitude modulation (PAM) fluorometer. Bacterial communities were analyzed using 16s rRNA gene sequencing. Corals in HS-supplemented microcosms had significantly higher photosynthetic activities than those in microcosms subjected to elevated temperature and UVB radiation. Additionally, HS supplementation significantly influenced the composition of sediment, water and host-associated bacterial communities. Reef organisms in HS supplemented microcosms contained distinct bacterial communities enriched with groups of potentially beneficial bacteria. In the hard coral Montipora digitata, we observed an interactive effect of HS supplementation, UVB radiation, and temperature.

Conclusion

Our findings indicate that HS significantly modulates coral reef bacterial communities and support the hypothesis that these substances contribute to improved reef resistance to the adverse effects of elevated temperature and UVB radiation.
Effects of GLP-1 receptor agonist therapy on resolution of steatohepatitis in non-alcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Potter Kathryn J , Phinney Jackie , Kulai Tasha , Munro Vicki
Published: January 2025

Background

Non-alcoholic fatty liver disease (NAFLD) is common, can progress to cirrhosis and hepatic decompensation, and has no approved medical therapy in Canada.

Objective

We conducted a systematic review on whether glucagon-like peptide-1 receptor agonists (GLP-1RA) improve non-alcoholic steatohepatitis (NASH) compared to standard care in NAFLD.

Methods

We searched Medline Ovid, EMBASE(Elsevier), Cochrane CENTRAL, Clinical Trials.gov, and the World Health Organization International Clinical Trials Registry Platform in November 2023 for randomized controlled trials. Inclusion criteria included patients ≥13 years with NAFLD receiving GLP-1RA for ≥6 months compared to standard care/placebo. Cochrane risk-of-bias 2.0 tool was used for each outcome. After screening results in duplicate, we performed meta-analysis and reported odds ratios (OR) for dichotomous and mean difference of change score for continuous outcomes.

Results

Six studies with 478 patients met inclusion criteria; 3 studies reported on the primary endpoint resolution of NASH. GLP-1RA likely leads to resolution of NASH (OR 4.45 (95% CI 1.92, 10.3)) and reduction in liver steatosis on imaging (–5.09% (95% CI −7.49, −2.69), but little to no reduction in liver stiffness on imaging (mean difference –0.17 kPa (95% CI −0.34, 0)).

Interpretation

Treatment with GLP-1RA in NAFLD patients for ≥6 months can probably lead to improvement in NASH on liver biopsy and reduce liver steatosis on imaging. Whether improvements in steatosis on biopsy or imaging results in clinically significant outcomes need to be elucidated as the effects of GLP-1RA on liver fibrosis are unclear; larger ongoing trials may provide more definitive answers.

Protocol Registration: PROSPERO–CRD42023472186.
Habitat-specific seasonal densities of sympatric raccoons and opossums in the southeastern United States
Authors: Hill Jacob E , Miller Madison L , Chipman Richard B , Gilbert Amy T , Beasley James C , Dharmarajan Guha , Rhodes Olin E
Published: January 2025

Raccoon and opossum densities have implications for rabies management, but estimates of seasonal densities of both species are lacking for rural nonagricultural habitats of the southeastern United States, a core portion of their geographic range. Consequently, it remains unclear whether the densities of 1 species limit the other, which is possible considering their substantial niche overlap. We carried out a mark–recapture study of raccoons and opossums in 4 rural nonagricultural habitats (bottomland hardwood forest, riparian forest, upland pine forest, and isolated wetlands) in South Carolina, United States (2020 to 2022), and combined this with previous data from the same habitats (2017 to 2019) to estimate habitat-specific spring and fall densities. Raccoon densities ranged from 5.17 ± 0.96 animals/km2 (bottomland hardwood fall) to 1.63 ± 0.83 animals/km2 (upland pine spring) and were on average 19% higher in fall compared to spring. Opossum densities ranged from 10.35 ± 1.98 animals/km2 (bottomland hardwood fall) to 1.11 ± 1.55 animals/km2 (upland pine spring) with divergent seasonal patterns among habitats. These low densities across all habitats compared to other studies are likely the result of low resource availability, consistent with other habitats that have minimal anthropogenic influence. We observed a positive association between raccoon and opossum densities across trapping grids, suggesting that raccoons do not suppress opossum densities, but that densities of both species increase with increasing resource availability. Our results can be used to inform oral rabies vaccination efforts such as refining bait densities and timing of bait distribution in these habitats.
Individualism and Emotional Attachment: An Evolving Tension in American History
Authors: Stearns Peter N
Published: January 2025

This article identifies and traces the rise of greater individualism in American history, from the early nineteenth century onward, and the corresponding effort to provide protective compensations, through associations, family ties, friendships, and sympathy for stresses such as homesickness and loneliness. The essay emphasizes several major stages in this often complex balancing act. Risks of tension increased in the twentieth century, with declining sympathy for some issues of adjustment, somewhat weaker family, and emotional ties. The situation deteriorated further after the 1950s, through a combination of new and more isolating forms of individualism, greater though diverse family instability and the now-familiar signs of growing loneliness. However, new forms of compensation must also be assessed, from the rise of pets to the unusually eager American reception of psychological therapy. The purpose of the article is to highlight an enduring basic theme in the nation’s emotional history—contributing to the growing interest in the history of emotions more generally—while also placing several urgent current problems in clearer historical context.
Risk of Oropouche virus importation to Southeast Asia via international travelers
Authors: Ali Qadija M , Imad Hisham A , Rodriguez-Morales Alfonso J , Matsee Wasin
Published: January 2025

We evaluate travel-associated Oropouche virus (OROV) infection and the potential of OROV importation into Southeast Asia (SEA) a region vulnerable due to rising international travel and the presence of competent vector, and explore key factors facilitating transmission, emphasizing the urgent need for enhanced surveillance, diagnostic tools and public health strategies.
Unstable accretion in TW Hya: 3D simulations and comparisons with observations
Authors: Romanova M M , Espaillat C C , Wendeborn J , Donati J-F , Petrov P P , Lovelace R V E
Published: January 2025

We investigate the origin of photometric variability in the classical T Tauri star TW Hya by comparing light curves obtained by TESS and ground-based telescopes with light curves created using three-dimensional (3D) magnetohydrodynamic (MHD) simulations. TW Hya is modeled as a rotating star with a dipole magnetic moment, which is slightly tilted about the rotational axis. We observed that for various model parameters, matter accretes in the unstable regime and produces multiple hot spots on the star’s surface, which leads to stochastic-looking light curves similar to the observed ones. Wavelet and Fourier spectra of observed and modeled light curves show multiple quasiperiodic oscillations (QPOs) with quasiperiods from less than 0.1 to 9 days. Models show that variation in the strength and tilt of the dipole magnetosphere leads to different periodograms, where the period of the star may dominate or be hidden. The amplitude of QPOs associated with the stellar period can be smaller than that of other QPOs if the tilt of the dipole magnetosphere is small and when the unstable regime is stronger. In models with small magnetospheres, the short-period QPOs associated with rotation of the inner disc dominate and can be mistaken for a stellar period. We show that longer-period (5-9 days) QPOs can be caused by waves forming beyond the corotation radius.
WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals
Authors: Zhang Shengjie , Dong Zi , Feng Yang , Guo Wei , Zhang Chen , Shi Yifan , Zhao Zhiyun , Wang Jiqiu , Ning Guang , Huang Guorui
Published: January 2025

Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice and cells, both of which exhibited dramatic mitochondrial changes. Subsequently, WBSCR16 was identified as a 16S rRNA-binding protein essential for the cleavage of 16S rRNA-mt-tRNALeu, facilitating 16S rRNA processing and mitochondrial ribosome assembly. Additionally, WBSCR16 recruited RNase P subunit MRPP3 to nascent 16S rRNA and assisted in this specific cleavage. Furthermore, evidence showed that adipose-specific Wbscr16 ablation promotes energy wasting via lipid preference in brown adipose tissue, leading to excess energy expenditure and resistance to obesity. In contrast, overexpression of WBSCR16 upregulated 16S rRNA processing and induced a preference for glucose utilization in both transgenic mouse models and cultured cells. These findings suggest that WBSCR16 plays essential roles in mitochondrial 16S rRNA processing in mammals, and is the key mitochondrial protein to balance glucose and lipid metabolism.
Measuring XNA polymerase fidelity in a hydrogel particle format
Authors: Medina Esau L , Chaput John C
Published: January 2025

Growth in the development of engineered polymerases for synthetic biology has led to renewed interest in assays that can measure the fidelity of polymerases that are capable of synthesizing artificial genetic polymers (XNAs). Conventional approaches require purifying the XNA intermediate of a replication cycle (DNA → XNA → DNA) by denaturing polyacrylamide gel electrophoresis, which is a slow, costly, and inefficient process that requires a large-scale transcription reaction and careful extraction of the XNA strand from the gel slice. In an effort to streamline the assay, we developed a purification-free approach in which the XNA transcription and reverse transcription steps occur inside the matrix of a hydrogel-coated magnetic particle. Accordingly, a DNA primer cross-linked throughout the gel matrix is annealed to a template of defined sequence and extended with XNA. Following removal of the DNA template, the XNA product strand is copied back into DNA, recovered, amplified, cloned, and sequenced. Performing the replication cycle in the hydrogel format drastically reduces the time and reaction scales required to measure the fidelity of an XNA polymerase, making it easier to evaluate the properties of a range of candidate XNA polymerases.
Multifaceted roles of H2B mono-ubiquitylation in D-loop metabolism during homologous recombination repair
Authors: Hung Shih-Hsun , Liang Yuan , Heyer Wolf-Dietrich
Published: January 2025

Repairing DNA double-strand breaks is crucial for maintaining genome integrity, which occurs primarily through homologous recombination (HR) in Saccharomyces cerevisiae. Nucleosomes, composed of DNA wrapped around a histone octamer, present a natural barrier to end resection to initiate HR, but the impact on the downstream HR steps of homology search, DNA strand invasion, and repair synthesis remain to be determined. Displacement loops (D-loops) play a pivotal role in HR, yet the influence of chromatin dynamics on D-loop metabolism remains unclear. Using the physical D-loop capture and D-loop extension (DLE) assays to track HR intermediates, we employed genetic analysis to reveal that H2B mono-ubiquitylation (H2Bubi) affects multiple steps during HR repair. We infer that H2Bubi modulates chromatin structure, not only promoting histone degradation for nascent D-loop formation but also stabilizing extended D-loops through nucleosome assembly. Furthermore, H2Bubi regulates DNA resection via Rad9 recruitment to suppress a feedback control mechanism that dampens D-loop formation and DLE at hyper-resected ends. Through physical and genetic assays to determine repair outcomes, we demonstrate that H2Bubi plays a crucial role in preventing break-induced replication and thus promoting genomic stability.
102. Carbapenemase producing organisms in Positive Blood and urine Cultures in a large New York Health System Reveals Emergence of NDM-Harboring Organisms and Associated Morbidity and Mortality
Authors: Haghamad Aya , Shou Ryan , An Kirby , Lemon Jamie , Juretschko Stefan , Streva Vincent
Published: January 2025

Background

Infections caused by organisms harboring carbapenemase genes are a significant cause of morbidity and mortality. The prevalence of carbapenemase producing organisms (CPO) has been increasing for several years, with the majority of isolates originating in healthcare settings and containing one of the five most prevalent carbapenemase genes (blaKPC, blaOXA-48-like, blaNDM, blaVIM, blaIMP). Management of patients with CPOs is particularly challenging and knowledge of the specific carbapenemase gene harbored by these organisms is imperative for proper treatment.

Methods

We conducted a retrospective multicenter study of hospitalized patients with blood and urine cultures positive for a CPO from January 2021 to December 2023 (2021-2023 blood, 2023 for urine). Blood culture PCR results were utilized to identify carbapenemase genes from these specimens. For urine specimens, phenotypic carbapenemase production was assessed by a lateral flow immunoassay (NG-Test CARBA 5). Clinical outcomes including time to appropriate therapy, length of hospital stay, 30-day hospital readmission, and patient mortality were evaluated.

Results

A total of 71 CPO-positive blood cultures and 50 CPO-positive urine cultures from 10 hospitals were included. Klebsiella pneumoniae was the predominant CPO isolated from both blood and urine samples, urinary tract infections was the most common source of CPO bacteremia. Of the carbapenemase resistance genes detected, blaNDM comprised 39% of CPO isolated from blood and 46% of CPO isolated from urine. Median time to appropriate therapy was 3.9 hours for blood cultures and 16 hours for urine cultures. The median length of hospital stay was 20 days for blood infections and 13 days for urine infections. Thirty-day readmission rates were 16% for blood infections and 50% for urine infections, with mortality rates of 39% for blood infections and 6% for urine infections.

Conclusion

Timely identification and differentiation of carbapenem resistance genes are crucial for informing adjustments in antimicrobial therapy. Despite appropriate clinical interventions patients with CPO bacteremia had elevated mortality rates, 42% in 2022 and 33% in 2023. Notably, the primary contributor to these high mortality rates was NDM, with rates reaching 54% in 2022 and 50% in 2023.

Disclosures

All Authors: No reported disclosures
171. Retrospective Review of Management of Acute Otitis Media in a Canadian Pediatric Emergency Department
Authors: Mhapankar Gunjan , Krueger Carsten , Alqurashi Waleed , Sucha Ewa , Webster Richard , Bowes Jennifer , Le Saux Nicole
Published: January 2025

Background

Acute Otitis Media (AOM) is a leading cause of antibiotic prescription in children. Watchful waiting is the preferred strategy for AOM management for mildly ill children ≥ 2-years-old however current clinical practice varies. This study aims to compare published AOM guidelines by the Canadian Pediatric Society (CPS) with clinical practice in a Canadian academic tertiary care emergency department (ED).

Methods

We performed a retrospective review on AOM ED visits at the Children’s Hospital of Eastern Ontario (CHEO) from 1/2021 to 12/2021. Measures of non-adherence to the CPS AOM guideline were defined as follows: missed opportunity for watchful waiting, diagnostic criteria absent or not recorded, prolonged duration of treatment, lack of immediate treatment, and inappropriate agent. Additionally we explored if guideline-discordant antibiotic prescribing practices differ by geographic locale (rural vs non-rural as determined by postal code) and preferred language. The postal code was linked to a Material and Social Deprivation Index (MSDI) from INSPQ as a proxy for socio-economic status.

Results

442 patients were included (Table 1). 66.5% patients met criteria of non-adherence (Table 2). 41.9% patients received antibiotics despite being categorized as mildly ill. 29.6% patients received antibiotics, despite having no/undocumented middle ear effusion or bulging tympanic membrane. 6.6% received longer duration of antibiotics (10 days) despite lack of complications such as perforation. 4.1% received non-penicillin antibiotics as first-line treatment. 1.4% received parachute prescriptions despite being categorized as severely ill. After controlling for language and rurality, the odds of being in any non-adherence group were not higher for patients in higher deprivation quintiles compared to those in the lowest deprivation quintile (Figure 1, 2).Figure 1.Distribution of Material Deprivation Quintiles by Non-adherence Type

Conclusion

2/3rd of ED patients met criteria of guideline non-adherence. Material deprivation was not a predictor of non-adherence. The two domains of watchful waiting and applying diagnostic criteria can serve as specific benchmarks to improve antibiotic prescribing practices in ED settings. Pragmatic management of AOM using current guidelines may be biased towards immediate treatment rather than timely follow-up.Figure 2.Odds ratio of any non-adherence for material deprivation quintile adjusted for language and rurality

Disclosures

All Authors: No reported disclosures
208. Exposure-response relationship of ceftazidime/avibactam in adults with central nervous system infections caused by carbapenem-resistant Klebsiella pneumoniae: a prospective observational study
Authors: Li Nanyang , Yang Lei , Zhu Xu , Li Wanzhen , Ye Xiangru , Gao Liang , Li Lei , Wu Jufang , Zhang Jing , Hu Jin , Mao Ying
Published: January 2025

Background

Central nervous system (CNS) infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) poses significant challenges for clinicians in ICU. Achieving optimal drug exposure in the cerebrospinal fluid (CSF) is crucial for good outcomes. This study aimed to evaluate the exposure-response relationship of ceftazidime/avibactam (CZA) in plasma and CSF.

Methods

All patients received CZA (2.5 g), IV infusion (over 2 hours), q8h. At steady-state after the fourth dose of CZA, the concentrations of CZA in the plasma and CSF were determined by ultra-performance liquid chromatography (UPLC) at 1, 2, 2.25, 2.5, 3, 4, 6, and 8 h post-dose. The PK/PD index of ceftazidime (CAZ) and avibactam(AVI) was calculated for each patient. Demographic, clinical efficacy, microbiological eradication, and 28-day mortality were reviewed. Blood and CSF samples were collected for calculation of PK parameters by non-compartmental pharmacokinetics (PK) modeling. The attainment of CAZ and AVI PK/PD targets in plasma and CSF was calculated to assess the exposure-response relationship of CZA and the corresponding clinical efficacy rate and bacterial eradication rate.

Results

CAZ and AVI demonstrated good penetration into CSF, evidenced by median CSF/plasma AUCtau ratio of 43.8 % and 55.8 %, respectively. CZA 2.5 g q8h achieved CAZ PK/PD target of 50%fT >MIC in both plasma and 50%T >MIC in CSF of all patients and reached AVI PK/PD target of 50%T >CT=1 mg/L in CSF of 80% (16/20) of patients. The dosing regimen also achieved CAZ PK/PD target of 100% fT >4MIC in plasma of 9 patients and 100% T >4MIC in CSF of 14 patients. At the end of the treatment, the overall clinical and microbiological efficacy rates were 80.0% and 100%, respectively. Only one case of CZA-related adverse event (Clostridioides difficile-associated diarrhoea) was reported.

Conclusion

The good CSF penetration of CZA enables the dosing regimen of CZA 2.5 g q8h a promising treatment option for CNS infections caused by CRKP.

Disclosures

Nanyang Li, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator Jing Zhang, Doctor of Medicine, TenNor Therapeutics (Suzhou) Ltd: Investigator
214. Clinical Characteristics and Outcomes of Patients Treated with Tecovirimat for Mpox Disease: A Large Cohort in New York City
Authors: Leocadio Ciarra , Garcia Elizabeth A , Lash Maura , Berardi Jonathan , Chan Justin , Chasan Rachel , Esquivel Blanca C , Foote Mary K , Glesby Marshall J , Guerra Amiyah , Harris Alexander B , Knutsen Dorothy , Mannheimer Sharon , Mazo Dana , McLean Jacob , McPherson Tristan D , Meyerowitz Eric , Mgbako Ofole , Patel Gopi , Pagán Pirallo Patricia , Radix Asa , Riska Paul F , Sayegh Mark N , Shaw Raphael , Zingman Barry S , Zomorodi Rustin A , Zucker Jason , Wong Marcia
Published: January 2025

Background

Clinical characteristics and outcomes in patients with mpox treated with tecovirimat are not well described.

Methods

We requested retrospective deidentified data from healthcare systems in New York City (NYC) with >50 tecovirimat prescriptions. Patients with probable or confirmed mpox initiating tecovirimat from May–December 2022 were included. We used a survey tool to extract demographic and clinical data from medical records. Patients reporting tecovirimat initiation at a different institution or with unknown HIV status were excluded. We used multivariable Poisson regression models with robust standard errors to examine factors associated with hospitalization and treatment delays.

Results

Of 751 eligible records, we excluded 41, leaving 708 patients in the analysis; median age was 36 years (IQR 31–43); 694 (98%) were assigned male at birth; 566 (80%) were cisgender men who have sex with men; 399 (56%) were living with HIV; and 232 (33%), 195 (28%), and 182 (26%) identified as Hispanic, non-Hispanic (NH) white, and NH Black, respectively. Reasons for treatment included proctitis (n=376, 53%), lesion type (confluent, location) (335, 47%), HIV (237, 33%), and bacterial superinfection (58, 8%). Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69,10%) (Table 1). Of 100 (14%) hospitalized patients, reasons for hospitalization included pain (25%), bacterial superinfection (22%), and dysphagia (13%) (Table 2). Median delay from symptom onset to treatment initiation was 8 days (IQR 6–11). NH Black patients had higher risk of initiating ≥8 days after symptom onset (adjusted relative risk [aRR]=1.4, 95%CI: 1.2–1.7) and being hospitalized (aRR=2.2, 95%CI: 1.4–3.5) compared with Hispanic patients, adjusting for HIV and insurance status (Tables 3,4).

Conclusion

We described common reasons for tecovirimat initiation and hospitalization. There were racial and ethnic disparities in hospitalization and treatment delays that may have been due to late presentation to care or provider-related delayed testing. More research and focused efforts to mitigate these disparities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox.

Disclosures

Ofole Mgbako, MD MS, Gilead: Advisor/Consultant
296. MDR Risk Index: Multidrug-Resistant Bacteria Probability Score for General Hospitals
Authors: Leite Edna M M , Camargos Esther , Aguiar Lilian , De Oliveira Wagner Luiz , Couto Bráulio R G M
Published: January 2025

Background

This research endeavors to shed light on the intricate relationship between hospitalization dynamics and the probability of acquiring multidrug-resistant bacteria (MDR) by introducing a predictive tool, the Multidrug-Resistant Bacteria Probability Score.Figure 1.Estimated Risk of MDR (Multidrug-Resistant Bacteria): Point Estimates and 95% Confidence Intervals.

Methods

We processed cultures in the hospital laboratory using automated systems and/or microdilution methods, adhering to the BR-cast guidelines. We utilized a logistic regression model to analyze four predictive variables for MDR: length of hospitalization until the collection of biological material (days), previous hospitalization (yes/no), duration of previous hospital stays (days), and admission to the Intensive Care Unit (ICU) (yes/no). The assessment focused on 7 outcomes: MDR (any type), resistance to Meropenem (RMER), production of Klebsiella pneumoniae carbapenemase (KPC), production of Extended Spectrum Beta-Lactamase (ESBL), resistance to Polymyxin (RPOL), Vancomycin-resistant Enterococci (VRE), and Methicillin-resistant Staphylococcus aureus (MRSA).Figure 2.Logistic Regression Models Estimating MDR Risk: Results for Each Type of MDR Bacteria.

Results

A total of 4,247 biological samples were collected from Nov/2022 to Nov/2023: Urine (46%), Blood (12%), Tissue Fragments (11%), Bronchoalveolar Lavage (6%), Perianal Swabs (6%), Tracheal Aspirates (4%), Nasal Swabs (3%), Abdominal Fluid (2%), Tips of Central or Umbilical Catheters (2%), Wound Secretions (1%), and Other (3%). Approximately one-third (35%) of the samples were identified as MDR. Unadjusted MDR risk: 9% RMER, 5% KPC, 8% ESBL, 1% RPOL, 3% VRE, and 4% MRSA (Fig. 1). From the seven outcomes modeled, it was possible to successfully predict five of them (Fig. 2), yielding good results in terms of predictive capability (Fig. 3). However, the modeling was unsuccessful for MRSA and ESBL. Figure 4 shows simulations of MDR risk.Figure 3.ROC Curves for the Five Successful Models Predicting Multidrug-Resistant Bacteria (MDR).

Conclusion

The duration of hospitalization prior to the collection of biological material emerges as a crucial metric, encapsulating the temporal dimension of patient exposure to potential sources of infection. All five predictive models can be effectively integrated into the patient’s electronic health record. This integration enables the timely prediction of multidrug-resistant (MDR) infections, facilitating the implementation of targeted preventive measures based on the assessed risk level.Figure 4.Simulation of MDR Risk Evolution Over Hospitalization Time: Curves Representing MDR Risk by Patient Type

Disclosures

All Authors: No reported disclosures
307. Respiratory Syncytial Virus (RSV) Infections Among Persons Aged 60 Years and Older, by Vaccination Status, reported via Electronic Laboratory Reporting (ELR) – Los Angeles County (LAC), California
Authors: Ransohoff Heidi , Frey Natalie A , Moir Olivia , Traub Elizabeth , Kim Andrea , Yeganeh Nava , de St. Maurice Annabelle
Published: January 2025

Background

On June 21, 2023 the CDC Advisory Committee on Immunization Practices recommended 2 different RSV vaccines for adults ≥ 60 years with shared clinical decision making. This study aims to compare the risk of laboratory-confirmed RSV infection in presumed vaccinated and unvaccinated adults ≥ 60 years living in LAC.

Methods

A population-based analysis was conducted using RSV vaccination data from the California Immunization Registry (CAIR), RSV positive case data reported to LAC Department of Public Health (DPH) via ELR between July 1, 2023 to March 20, 2024, and July 1, 2022 Population Estimates (provisional), prepared by Hedderson Demographic Services for Los Angeles County Internal Services Department, released March 2023. The study population included LAC residents ≥ 60 years at time of specimen collection. The data were matched on name, date of birth, and street address. Vaccinated cases were defined as persons who had CAIR record of RSV vaccination ≥ 14 days before specimen collection.

Results

The population of LAC residents ≥ 60 years is estimated at 2,076,677; 240,861 had RSV vaccinations in CAIR. 2,296 were ELR RSV cases: 58 (2.5%) were vaccinated; 2,238 (97.5%) were unvaccinated. The risk of ELR RSV infection among unvaccinated persons was 5.1 times higher than among vaccinated persons (Table 1; RR= 5.1; 95% CI 3.7:5.1, p < 0.001). Most cases were older than 74.

Conclusion

The results show that unvaccinated older adults in LAC had a higher risk of ELR RSV infection than those who were vaccinated. Limitations include possible incomplete data in CAIR and ELR, making infection risk estimates imprecise. Future studies using these data sources may include hospitalization and death data to compare the incidence of serious illness in vaccinated and unvaccinated adults.

Disclosures

All Authors: No reported disclosures
P-811. Telavancin for Refractory MRSA Bacteremia: A 10-Year Retrospective Review
Authors: Gander Caroline , Singanamala Santhi , Holzworth Abriana , Rux Caleb , McManus Dayna , Davis Matthew W , Topal Jeffrey E
Published: January 2025

Background

Refractory methicillin-resistant Staphylococcus aureus (MRSA) bacteremia continues to represent a challenge in clinical treatment. Telavancin, a lipoglycopeptide with multiple mechanisms of action, has been proposed as a treatment option in these cases.

Methods

This was a single-center, retrospective chart review of adult inpatients with refractory MRSA bacteremia (defined as > 72 hours of bacteremia following the start of daptomycin or vancomycin) who were treated with telavancin from December 2014 through March 2024. Patients who died or were discharged within 72 hours of starting telavancin or whose blood cultures cleared prior to the start of telavancin were excluded. More details can be seen in figure 1. The primary outcome was clinical success, defined as blood culture clearance on telavancin monotherapy. Secondary outcomes included length of time to blood culture clearance following telavancin initiation, recurrence of bacteremia within 30 days of clearance, and 30- and 90-day mortality from the time of telavancin initiation.

Results

Of 105 patients who received telavancin, 77 met inclusion criteria. Of the patients who received telavancin, 56 (72.7%) met the primary outcome, and cleared the refractory MRSA bacteremia with telavancin monotherapy. Patients who failed telavancin included 11 who did not clear blood cultures before death, 2 who cleared on telavancin plus an additional agent, and 8 who cleared after switching from telavancin to another salvage regimen. Minimum inhibitory concentrations (MICs) ranged from ≤0.5 to 2 for vancomycin, 0.094 to 2 for daptomycin, and 0.016 to 0.38 for telavancin. Other baseline characteristics can be seen in table 1. No significant differences in baseline characteristics were seen between groups. The median time to culture clearance among the clinical success group was 57 hours. Only 1.8% of these patients had recurrent bacteremia within 30 days of telavancin initiation. At 30 days from telavancin initiation, overall mortality was 21.4%, and at 90 days, 23.2%.

Conclusion

In patients with refractory MRSA bacteremia, telavancin may be a viable monotherapy salvage regimen, with mortality rates similar to those previously reported for all patients with MRSA bacteremia.

Disclosures

All Authors: No reported disclosures
P-837. Characteristics, Predisposing Factors And Clinical Outcomes of Patients with Probiotics Organisms Bacteremia
Authors: El Soufi Hind , Dahal Santosh , Doan Thien-Ly , Sohail Rubab , Sison Cristina , Akerman Meredith , Hirsch Bruce
Published: January 2025

Background

Bacteremia with probiotic organisms is rare. Patients’ characteristics and clinical outcomes are not well known. Our objective is to study the characteristics, risk factors and outcomes of patients with different probiotic organisms’ bacteremia.

Methods

This is a retrospective observational study of patients with probiotic organisms’ bacteremia, admitted to a New York Health system, between 2018 and 2021. 143 patients were divided into 2 cohorts. Cohort 1 (85.3%) had Lactobacillus spp bacteremia and Cohort 2 (14.7%) had positive blood culture with Saccharomyces spp or Bifidobacterium spp. Descriptive statistics were reported for patients’ characteristics, past medical history (PMH) and hospital related history (HRH). Chi-square or Fisher’s exact test was used for categorical variables and T-test or Wilcoxon test for continuous variables. Logistic regression was used to compare 30-day in hospital mortality and 30-day hospital readmission for a related infection. Negative binomial regression was used to compare hospital length of stay, duration of therapy targeted for probiotic bacteremia and number of days until blood culture clearance. P value < 0.05 was considered statistically significant.

Results

50.3% were male, 59.1 % were white, 2.8 % were Hispanic or Latino. 7% had prior bacteremia within 6 months, 30.8% had concurrent bacteremia and 10.5% had concurrent fungemia with other than the probiotic organism. Patients with probiotic bacteremia (PB) had frequent comorbidities: 48% had hypertension, 36% had Diabetes Mellitus, 14.7% were immunosuppressed. 44% had central line during hospitalization, 42% had qSofa score >2. PB was associated with prolonged length of stay (Mean in days 20.4) and 30-day in hospital mortality (34.3%). There were no statistical differences in PMH, HRH and outcomes between the Lactobacillus spp group and other group.

Conclusion

PB occurs in hospitalized patients with frequent comorbidities and advanced clinical illness. Caution is required in administration of probiotics in vulnerable patients.

Disclosures

All Authors: No reported disclosures
P-838. The effect of transesophageal echocardiogram on clinical decision making for patients with Staphylococcus aureus blood stream infection
Authors: Shaikhli Hiba Al , Wingler Mary Joyce B , Stover Kayla R , Cretella David A , Barber Katie , Wagner Jamie
Published: January 2025

Background

Staphylococcus aureus can lead to severe infections, including bloodstream infections, which are associated with high mortality. Infective endocarditis (IE) is a concerning complication of S. aureus bloodstream infections (SABSIs), which is ruled out by transesophageal echocardiogram (TEE). The COVID-19 pandemic led to a decrease in TEEs at the University of Mississippi Medical Center (UMMC) for patients with SABSIs. This study explores the impact of reduced TEE rates on clinical decisions for SABSI patients.

Methods

This retrospective observational study assessed adult SABSI patients at UMMC, categorizing them into pre-COVID (admitted between 3/1/2018-3/11/2020) and COVID (admitted between 3/12/2020-3/1/2022) groups. A VIRSTA score, indicating IE risk and advocating TEE for high-risk patients (score ≥3), was calculated for patients. Primary outcomes included the rate of confirmed IE and antibiotic duration in pre-COVID and COVID groups. Secondary outcomes included hospital stay, correlation between VIRSTA score and TEE, 90-day mortality, and 60-day re-admission.

Results

Among 214 patients, baseline characteristics were comparable between groups. The rate of confirmed IE (9.4% pre-COVID vs. 12.1% COVID; p = 0.66) and median antibiotic duration (28 days in both groups) showed no significant differences. However, mortality was more likely in the COVID group (22.2% vs 10.4%; p=0.019). Notably, high VIRSTA score patients were less likely to undergo TEE COVID (3.8% vs 18.5%; p = 0.008). There were no differences in other secondary outcomes.

Conclusion

This retrospective study highlights the impact of reduced transesophageal TEE utilization during the COVID-19 pandemic on clinical decision-making for patients with SABSIs, including challenges in risk stratification based on VIRSTA score. Despite a decrease in TEE, there were no differences in confirmed IE diagnosis or duration of antibiotics, but mortality was higher in the COVID-19 group. Based on this study there is an opportunity to provide education related to VIRSTA score utility for risk stratification, which may preserve healthcare resources in select patients.

Disclosures

All Authors: No reported disclosures
P-843. Enhancing Bacteremia Mortality Predictions: A Comparative Study of Machine Learning Models Across Databases
Authors: Kurian James , Adelman Max W , Arias Cesar A , Casarin Stefano , Connor Ashton , Contreras German , Nigo Masayuki
Published: January 2025

Background

Bacteremia is a major cause of morbidity and mortality in hospitals, and multiple scoring mechanisms have been developed to help with risk assessment. In the setting of bacteremia, the Pitt bacteremia score (PBS) has been used. This study develops ML models to predict mortality in bacteremic patients, comparing their performance against the PBS.

Characteristics of Patients

ECI: Elixhauser Comorbidity Index

Methods

We retrospectively identified patients aged over 18 years who developed bacteremia in the Houston Methodist Hospital System (HMH) from June 2016 to June 2023. True bacteremia was defined based on CDC definitions. MIMIC-IV data, a comprehensive, de-identified electronic health record (EHR) database of critical care patients from Boston, USA, served as an external validation dataset. We recorded maximally perturbed values of 34 clinical and laboratory variables within 48 hours before the first bacteremia. Missing values were imputed using multiple imputation chain equation (MICE) method after preprocessing datasets. Each dataset was split into 70:30 training and test datasets. Models including PBS, Logistic Regression (LR), Random Forest (RF), LightGBM (LGBM), and XGBoost (XGB), along with hyperparameter tuning via Optuna, were used in classification tasks to predict 30-day all-cause mortality. AUROCs (Area Under the Receiver Operating Characteristics) for each model on test dataset were created, and they were statistically compared with DeLong’s tests. Probability cutoffs for each model were decided to maintain a specificity close to 95%.

Model Performance of ML Models and Pitts Score against Mortality

Results

Across HMH and MIMIC-IV, 21,972 and 2,439 patients experienced BSIs, respectively. Table 1 summarizes characteristics of the patients. E. coli and Enterococcus spp. were the most common pathogens in HMH and MIMIC-IV, respectively. S. aureus made up 17% of bacteremia. All the ML models exhibited higher AUROCs than that of the PBS. LGBM and XGB achieved the highest AUROCs of 0.878 and 0.824, respectively, surpassing PBS (p < 0.05).

Conclusion

ML models demonstrated higher AUROC and superior performance than that of PBS. ML allows for vast quantities of input data. This ability to process and integrate diverse features may contribute to personalized medicine in infectious diseases.

Disclosures

All Authors: No reported disclosures