bluuebunny/crossref_metadata_2025 huggingface dataset:
P-449. Healthcare Burden of Venous Thromboembolism (VTE) among People Living with Human Immunodeficiency Virus (PLHIV): A Nationwide Inpatient Data Analysis (2019-2021)
Authors: Macaraeg Chef Stan L , Aldecoa Kim Abbegail , Vergara Cunegundo
Published: January 2025

Background

Venous Thromboembolism (VTE) imposes a substantial economic burden, estimated to incur almost $10 billion each year. People Living with Human Immunodeficiency Virus (PLHIV) face an almost two- to tenfold higher risk of developing VTE compared to the general population. However, limited data exists on the healthcare burden of VTE among PLHIV. The study investigated the healthcare burden of VTE among PLHIV compared to non-HIV patients. Additionally, the study examined the difference in sociodemographic factors between the two groups.

Methods

We analyzed data from the National Inpatient Sample database from 2019 to 2021 to identify all hospitalizations with a primary diagnosis of Acute Venous Thromboembolism. Subsequently, we categorized patients into HIV and non-HIV groups. Stata 18.0 was utilized for analysis, with a p-value < 0.05 indicating statistical significance. Hospital costs were adjusted for inflation using the US Consumer Price Index.

Results

Among the 821,494 hospitalizations for VTE, 2230 patients had HIV infection. HIV patients were significantly younger (52.5 vs. 63.4 years) and predominantly male, Black (56.3% vs. 20.0%), and Hispanic (11.3% vs. 7.2%) individuals. The HIV group exhibited longer hospital stays (6.23 vs. 4.37 days) and incurred higher total hospital costs ($19,117 vs. $14,115) after adjusting for age and sex. Notably, there was a positive correlation between length of stay and hospital costs (r=0.68, p< 0.001). The incidence of AKI and pneumonia significantly prolonged hospital stays in the HIV subgroup (aOR: 2.96, 95% CI: 1.21-4.70; aOR: 2.92, 95% CI: 0.42-5.42). From 2019 to 2021, hospital costs showed a significant increase ($18338, $20330, $24507, p=0.034), while the hospital length of stay displayed an increasing trend but was not statistically significant (mean in days: 5.9, 6.4, 7.0, p=0.147). There was no specific trend observed in the VTE rate each year (0.28%, 0.26%, 0.28%, p=0.7875) among the HIV subgroup.

Conclusion

The healthcare burden of VTE hospitalization is higher among PLHIV. There has been a concerning increasing trend in hospital costs among PLHIV from 2019 to 2021. Future studies should investigate additional factors contributing to this healthcare burden to enhance the cost-effectiveness of care.

Disclosures

All Authors: No reported disclosures
P-477. What Can be Learned from Vermonters Living with HIV Viremia?
Authors: Pilcher Finlay , Tompkins Bradley , Lynn Keara , Singh Devika
Published: January 2025

Background

Lower rates of viral suppression have been identified in people living with HIV (PLHIV) residing in rural compared to metropolitan areas. This is a barrier to ending the HIV epidemic in the US, and thus represents an urgent focus topic.

Vermont is a rural state with roughly 700 PLHIV. Vermonters living with HIV tend to be rigorously engaged into clinical care and have high rates of viral suppression. Yet, there are PLHIV in Vermont that have unsuppressed viral loads, and little is known about the characteristics of this cohort.

Our study aims to epidemiologically describe Vermonters with an HIV viral load greater than 200 copies/mL. This characterization can aid in appropriate allocation of resources and improve our understanding of PLHIV with viremia residing in rural areas.

Methods

Our study used electronic health record data from Epic Systems Corporation (Epic) from 2019 and 2020. We included PLHIV from three infectious disease clinic sites within the University of Vermont Health Network (UVMHN; n = 456) that had at least one clinical visit in the past 18 months. The following data were extracted from patient charts: HIV detection and quantitation, clinic location, race, sexual orientation, and substance use.

Results

The results of our study are shown in Tables 1 and 2. There was no significant association between clinic location, race, sexual orientation, or substance use and having a viral load greater than 200 copies/mL.

Conclusion

Our results suggest that in Vermont, the presence of viremia in PLHIV cannot be easily predicted by clinic location race, sexual orientation, or substance use. The authors suggest that traditional clinical markers including low CD4 counts, HIV resistance mutations, pill burden, older age and concomitant clinical comorbidities (dementia, etc.) may be more reliable factors associated with active viremia.

Although Vermont is demographically distinct from other rural areas, its residents share many barriers related to HIV care, including long travel distances to visits, limited HIV provider availability, and limited access to harm reduction services. These challenges necessitate our continued efforts to better understand and serve PLHIV living in rural areas to improve HIV equity and ultimately end the HIV epidemic.

Disclosures

All Authors: No reported disclosures
P-497. Performance of the Brief Patient Health Questionnaire-2 and Generalized Anxiety Disorder-2 Screeners for Identifying Depression and Anxiety in People with HIV
Authors: Lee Ye Eun , Latimer Maria C , Kelly Sharon , Verinumbe Tarfa I , Agee Tracy , Hutton Heidi , Jones Joyce L , Schwartz Sheree R , Hsu Jeffrey H , Falade-Nwulia Oluwaseun
Published: January 2025

Background

Mental health disorder (MHD) prevalence is high among people with HIV (PWH) and linked to poor health outcomes, including HIV non-suppression. Despite recommendations for routine mental health screening in HIV care settings, screening uptake remains low. The brief Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) are validated screeners for depression and anxiety symptoms with potential for integration into HIV care. This study evaluates the accuracy of the PHQ-2 and GAD-2 in detecting depression and anxiety among PWH and co-occurring MHD or substance use disorders (SUD).

Methods

Routine screening using the PHQ-2, GAD-2, and NIDA Quick Screen for SUD was implemented in an HIV care setting in Baltimore in April 2022. Patients who screened positive on any screener and enrolled in a study evaluating an intervention for SUD and MHD care were included in the analysis. Participants completed the longer PHQ-8 and GAD-7 screeners at enrollment, which served as reference standards using recommended cut points of ≥10 to indicate moderate or severe depression or anxiety, respectively. PHQ-2 and GAD-2 scores are derived from the first two questions of their corresponding longer measure. Area under the curve (AUC), sensitivity, and specificity were obtained for the PHQ-2 and GAD-2 at various cut points against their corresponding longer measure.

Results

Of the 204 patients included in this study, 68% were male, 80% were Black, and mean age was 51 years. Compared to the PHQ-8 using a cut point of ≥10, the PHQ-2 at the cut point of ≥3 demonstrated high accuracy in detecting depression at a cut point of ≥3 (AUC = 0.86; 95% CI: 0.81, 0.91) with a sensitivity of 0.82 (95% CI: 0.72, 0.89) and specificity of 0.90 (95% CI: 0.83, 0.95). Compared to the GAD-7 using a cut point of ≥10, the GAD-2 was highly accurate in identifying anxiety at a cut point of ≥3 (AUC = 0.90; 95% CI: 0.86, 0.94), achieving a high sensitivity (0.89; 95% CI: 0.81, 0.95) and specificity (0.91; 95% CI: 0.84, 0.95).

Conclusion

In the context of HIV care in busy clinical settings, our findings indicate that implementation of the PHQ-2 and GAD-2 screeners accurately detect depression and anxiety symptoms at the optimal cut point of ≥3. Simplified identification and treatment of comorbid MHD may improve HIV outcomes.

Disclosures

Oluwaseun Falade-Nwulia, MBBS ,MPH, Abbvie Inc: Grant/Research Support|Gilead Sciences: Advisor/Consultant
P-566. Long-term virologic outcomes of oral two-drug vs three-drug antiretroviral regimens in children, adolescents and adults living with HIV
Authors: Byrne Morgan , Koay Wei Li A , Unternaher Justin , O’Connor Lauren , Monroe Anne , Denyer Rachel V , Castel Amanda Derryck , Rakhmanina Natella
Published: January 2025

Background

Despite the availability and efficacy of two-drug regimens (2DR) for HIV treatment, three-drug regimens (3DR) are mostly used by people with HIV (PWH). We evaluated virologic outcomes of initiating or switching to a 2DR vs 3DR among PWH in Washington, DC.

Adjusted Cox Proportional Hazard Regression Model for Virologic Non-Suppression (viral load > 200 copies/mL) among PWH by Two- and Three-Drug Regimens in the DC Cohort, 2019-2023

Methods

We included DC Cohort treatment-experienced participants initiating or switching to a 2DR or 3DR on or after July 2019 with ≥2 years of follow-up. Descriptive statistics for demographic and clinical factors at regimen initiation, including HIV viral load (VL) and CD4 count (cells/µL), were stratified by 2DR or 3DR. Multivariable Cox proportional hazard modeling was performed among participants virally suppressed (VS; VL< 200 copies/mL) at regimen initiation to assess the time to non-virologic suppression (non-VS) using adjusted hazard ratios (aHR) and 95% CI adjusting for demographics, HIV risk, and regimen. Among participants who were not VS at the time of regimen initiation, we conducted a sub-analysis of the time to VS.

Results

We analyzed 1782 participants (72.8% 3DR, 28.2% 2DR (161 switched from a 3DR); age 54.3 years (IQR 43.8-61.3), 68.8% male; 78.1% Black) with a median CD4 621 (IQR 409-868) at regimen initiation. Participants on 2DR were older (56.4 vs 53.6 years; p< 0.001) and had higher VS rates (93.8% vs 88.2%; p< 0.001) at regimen initiation and shorter regimen times (3.2 vs 3.8 years; p< 0.001) compared to 3DR. 2DR participants were more likely to have public vs private insurance and receive hospital vs community-based care. The risk of non-VS was higher among those with CD4 < 200 and 200-500 (aHR 1.5(1.0-2.1) and aHR 2.0(1.1-3.6), respectively) compared to those with CD4 >500. Those with public insurance were also more likely to experience non-VS (aHR 1.5; p< 0.05). While regimen type was not a significant predictor of non-VS, there was an elevated risk among those on 3DR (aHR 1.2) compared to 2DR [Figure]. Among those non-VS at regimen initiation (n=146), the median time to VS was similar among PWH on 2DR (14.1 months) and 3DR (13.8 months; p=0.76).

Conclusion

Non-VS PWH have similar time to VS regardless of whether they receive 2DR or 3DR, suggesting similar efficacy of 2DR and 3DR in these populations. Patients with CD4 < 500 had higher risk of non-VS on 2DR, supporting the usefulness of the CD4 criteria factor when selecting 2DR vs 3DR.

Disclosures

All Authors: No reported disclosures
P-567. Baseline Patient and Clinician Results for the Pilot Project I-CARE-4-PAH (

I

ntervention for

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ollaborative

C

are to

A

ssess

R

isk and

E

liminate poly

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armacy,

F

alls, and

F

ragility

F

ractures for

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eople

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ging with

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IV)
Authors: Womack Julie A , Johnson Chloe , Danvers Karina , Hsieh Evelyn , Lauro Michael , Marottoli Richard , Murphy Anne , Payne Erika , Sheehan Lisa , Stewart Wynnett , Virata Michael D , Barakat Lydia A
Published: January 2025

Background

More than half of people living with HIV in the United States are 50 years of age or older. Understanding how best to assess and address conditions associated with aging in HIV primary care is important for this population.

Methods

We trained clinicians in an academic HIV clinic to assess and address the 4F’s (polypharmacy, Falls, and Fragility Fractures) in their patients aging with HIV (PAH). We share results of this screening as well as key knowledge, attitudes, and practices (KAP) from the pre-test assessment of our clinician champions.

Results

126 patients 50+ years of age were enrolled. The mean age is 63±6 years. 49% were assigned female at birth and 1% are transwomen. 48% identify as Black, 48% White, and 14% Hispanic. 30% smoke tobacco, and 30% report ongoing marijuana use. Patients take 10±5 medications; 25% have hyperpolypharmacy ( >15 medications), and 66% are on potentially inappropriate medications (PIMs). At least a quarter of patients have peripheral neuropathy: 25% have decreased sensation on the plantar surface of either foot; 35% have decreased vibratory sense on the right great toe,37% on the left. 42% reported a fall/near-fall in the past year; 10% experienced a serious fall leading to a visit with a healthcare provider. Mean risk of a serious fall in the next year is moderate: 4.05%±4.13%. 34% reported a fracture as an adult. Mean FRAX scores indicate a low 10-year risk for fragility fracture (major osteoporotic fracture: 8.71%±6.95%; hip fracture 2.11%±3.58%).

Eleven HIV clinicians are engaged with this project. Most (73%) regularly perform medication reconciliation. 55% report asking about falls only if the patient brings it up. 18% have never assessed their patients for fracture risk, and 36% have done so once.

Conclusion

Polypharmacy, peripheral neuropathy, PIMs, falls, and fractures are important intersectional risk factors for adverse outcomes in PAH and are inconsistently assessed by clinicians. Medication reconciliation is an important first step in identifying polypharmacy. Deprescribing, identifying patients with peripheral neuropathy, and discussing fall prevention are key foci for future interventions. Providing training resources for HIV clinicians to assess and prevent the 4F’s is crucial and feasible.

Disclosures

Richard Marottoli, MD, MPH, The Hartford: Advisory Panel on Older Driver Safety Michael D. Virata, MD, FACP, Janssen: Advisor/Consultant|Janssen: Honoraria|ViiV Pharmaceuticals: Advisor/Consultant|ViiV Pharmaceuticals: Honoraria
P-612. Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children: Data from the 2023/24 Influenza Season
Authors: Bandell Allyn R , Barker Chris , Dibben Oliver
Published: January 2025

Background

Annual vaccination with a live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV) is the most effective way to protect children from the burden of influenza infection, and to reduce the potential for transmission to family members and the community. Here we report vaccine effectiveness (VE) from data reported globally for LAIV and IIV in children from the 2023/24 influenza season.

Methods

Quadrivalent LAIV and IIV effectiveness studies conducted in children in the 2023/24 influenza season were identified from published literature and public health websites. Studies from Canada, Finland, the UK, the US, and a European-wide study in 10 countries, reporting VE data for any influenza infection (all strains), by strain type (all influenza A, A/H3N2, and A/H1N1pdm09), and by vaccination setting (primary/outpatient care and hospital) were included.

Results

In five studies reporting on influenza infections (all strains) in children with ages ranging from 6 months to 19 years across studies, VE estimates for LAIV ranged from 36% (95% CI: 21–48) in Finland to 65% (95% CI: 41–79) in the UK, and for IIV ranged from 59% (95% CI: 48–67) to 67% (95% CI: 48–80) in the US. When analyzed by vaccination setting, VE against any influenza, influenza A, A/H3N2, and A/H1N1pdm09 in all the included countries ranged from 36–65% for LAIV and 46–85% for IIV in children in primary/outpatient care (Figure 1). For hospitalized children, VE against any influenza, influenza A, A/H3N2, and A/H1N1pdm09 in all the included countries ranged from 25–80% for LAIV and 46–61% for IIV (Figure 2). Where available, VE data against influenza A, A/H3N2, and A/H1N1pdm09 were comparable for both LAIV and IIV in children in primary/outpatient care and hospitalized children.

Conclusion

VE data for the 2023/24 season from global reports show LAIV and IIV demonstrated comparable moderate protection for children against influenza infection. These early VE data were similar across the included healthcare settings of outpatient/primary care and hospitals.

Disclosures

Allyn R. Bandell, PharmD, AstraZeneca: Stocks/Bonds (Public Company) Chris Barker, PhD, AstraZeneca: Stocks/Bonds (Public Company) Oliver Dibben, PhD, AstraZeneca: Stocks/Bonds (Public Company)
P-651. An Artiﬁcial Intelligence Model Outperformed Experienced Clinicians in Differentiating the Aetiology of Pneumonia on Chest Computed Tomography: A Retrospective Study
Authors: Jin Wenting , Shao Ying , Gao Yaozong , Hu Bijie
Published: January 2025

Background

Rapid and precise aetiological diagnosis is crucial for managing pneumonia. We aimed to develop and validate deep learning (DL) models for differentiating ten pneumonia aetiologies on chest computed tomography images.

The area under the receiver operating characteristic curve (ROC) and the area under the curve (AUC) for the two deep learning models, the performance of four different radiologists and four different pulmonologists (A-B); The ROC and AUC of two models in identifying 10 different classifications (C-F).

Abbreviation: BP, bacterial pneumonia; AP, atypical pneumonia; PN, pulmonary nocardiosis; PTB, pulmonary tuberculosis; PNTM, pulmonary nontuberculous mycobacterial infection; PC, pulmonary cryptococosis; PA, pulmonary aspergillosis; PJP, pneumocystis jirovecii pneumonia, LC, lung cancer; PM, pneumonia mimics; Ra, radiologists; Pu, pulmonologists.

Methods

We enrolled 1091 pneumonia patients with one of 10 definite aetiological diagnoses from Zhongshan Hospital between Oct. 1st, 2015, and Jun. 30th, 2022, in this retrospective observational study. We trained and validated two DL models: a classic 3D-DenseNet model and a novel large vision model (LVM). The models were tested on a data from 59 nonoverlapping patients for external dataset. Model performance was assessed using the area under the curve (AUC) of the Top1 diagnosis and the accuracy of the Top1, Top2, and Top3 diagnoses. Comparisons were also performed between the DL models and eight experienced radiologists and pulmonologists.

The accuracy of Top1, Top2 and Top3 diagnoses of two deep learning models, radiologists and pulmonologists with or without nonimaging data

Abbreviation: LVM, large vision model; Note: + means with nonimaging data

Results

The LVM+ had a greater average prediction performance than DenseNet+, radiologists+ and pulmonologists+, with Top1 AUCs of 0.872, 0.851, 0.643 and 0.644, respectively. The Top1, Top2, and Top3 accuracies of LVM+ were 0.527, 0.701 and 0.820, respectively, similarly outperforming DenseNet+, radiologists+ and pulmonologists+. The two models performed similarly in the external test sets, with AUCs of 0.775 for LVM and 0.743 for DenseNet. The classification-related confusion matrix of LVM/DenseNet showed a significant advantage in identifying PNTM and PJP.

Conclusion

This study represents the most complete classification that best matches the diagnosis of pneumonia in realistic clinical settings. We expect this method to be applied clinically to foster novel approaches to improve the accuracy in diagnosing pneumonia.

Disclosures

All Authors: No reported disclosures
P-664. Trends in Bacterial Pneumonia-Related Mortality Among Older Adults in the United States
Authors: Ali Shah M Danial , Aslam Sadaf , Casanas Beata
Published: January 2025

Background

Bacterial pneumonia is one of the leading causes of mortality in the US, particularly among those aged 65 and older. No study has been done on this population to understand mortality patterns based on demographic characteristics such as age, gender, race, and geographic regions, which helps to enhance evidence-based interventions for this vulnerable age group.

Trends in Bacterial Pneumonia-related AAMRs and APC stratified by race in older adults.

Methods

This study involves a two-decade CDC WONDER data on bacterial pneumonia-related deaths via ICD-10 codes A48.1 and J13-J16.0 in ≥ 65-year-olds from 1999-2019. Demographic disparities are analyzed based on age, gender, race, census region, and urban-rural classification using systematic database analysis. Age-adjusted mortality rates (AAMRs) per 100,000 and annual percent change (APC) with a 95% Confidence Interval (CI) are calculated through joinpoint regression analysis.

Trends in Bacterial Pneumonia-related AAMRs in Black and White men and women.

Results

155,819 individuals aged ≥65 died from bacterial pneumonia in the US from 1999 to 2019. Initially, AAMR declined (1999-2005: APC -0.47; 95% CI -1.53 to 1.08), followed by a steep decline (2005-2010: APC -6.25; 95% CI -9.72 to -4.51), and concluded with a significant increase (2010-2019: APC 1.97; 95% CI 1.09 to 3.12). Males had higher AAMR (23.6) than females (14.2). Hispanics (19.6) were more affected than non-Hispanics (17.8) and Blacks more than Whites, except for White men (23), surpassing Black women (15.3). Pneumonia mortality varied by region, highest in Arizona and California (44.5 and 30.4) and lowest in New Jersey and Wisconsin (8 and 9.4). Nationwide, Black/White mortality is comparable except for the Northeast, where Black mortality doubles that of Whites.

Trends in Bacterial pneumonia-related AAMRs stratified by census regions. *=significant at p < 0.05; confidence interval does not include zero.

Conclusion

While initial reductions in bacterial pneumonia-related mortality among older U.S. adults were observed, an upward trend from 2010 to 2019 negated this progress, resulting in a concerning resurgence. This upsurge disproportionately impacts specific demographics, including those aged 85 and older, males, non-Hispanic Blacks, those in the Western U.S., and urban populations. To further reduce mortality rates, this highlights the urgent need for effective interventions, improved access to care, and age-specific preventive programs. Further research is required to understand contributing factors.

Bacterial Pneumonia-related crude mortality percentage stratified by different variables between men and women.

Disclosures

All Authors: No reported disclosures
P-665. Etiology of Pneumonia and Antibiotic Resistance in Adults with Cancer in the ICU of a Tertiary Care Centre in Eastern India: a Prospective Cohort Study
Authors: Malik Simran , Bhattacharya Sanjay , Das Bhattacharya Sangeeta
Published: January 2025

Background

Cancer and its treatment cause immune-dysregulation which, along with frequent healthcare exposure, poses a higher risk of respiratory infections, frequently with unusual pathogens that can be highly drug-resistant. We assessed the etiology of pneumonia in adult cancer patients admitted to the ICU over one year and summarized the antibiotic resistance seen.

Methods

Pneumonia cases were identified from October 2022-September 2023. Sputum, endotracheal secretion, bronchoalveolar lavage (BAL), tracheal aspirate, nose and throat swab samples from -4 to +10 days of the date of event were considered. Microbiological diagnosis involved microscopy, culture, ELISA, PCRs, and CBNAATs. Antibiotic susceptibility was determined phenotypically by disc-diffusion and genotypically using PCR tests for MRSA, ESBL, carbapenemase, and polymyxin resistance genes.

Results

355 cases of pneumonia were identified. 258 (72.7%) cases of had a positive microbiology, 123 were polymicrobial (47.7%) and termed “co-infections/ superadded infections". Table 1 summarizes the etiology of microbiology positive cases.

Antibiotic susceptibility data was available for 191 isolates, 14 were Staphylococcus aureus (table 2) and 177 were Gram-negatives (table 3). S. aureus have fluoroquinolones. 30.4% were MRSA and 21.4% showed inducible clindamycin resistance.

Gram negatives were resistant to third-generation cephalosporins, beta-lactam/beta-lactamase inhibitors, carbapenems, aminoglycosides, fluoroquinolones and cotrimoxazole, though variations exist across genera. 51% Gram negative isolates were positive for ESBL, 5.8% for AmpC, 9.7% were polymyxin resistant, and 49.5% were resistant to carbapenems. Carbapenem resistance genotypes are summarized in table 4.

Conclusion

Isolates from adult cancer patients with pneumonia showed high prevalence of resistance to all first-line antibiotics.

Disclosures

All Authors: No reported disclosures
P-666. Impact of Ceftriaxone Duration in Community-Acquired Pneumonia: A Retrospective Comparative Analysis
Authors: Ureta Lyle , Aprelian Kevin , Jung Hemi , Lin Theresa , Kawaguchi Keitaro , Hernandez Delia Duenas , Eskandarian Romic , Lee Su
Published: January 2025

Background

In accordance with the American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP), ceftriaxone plus a macrolide is commonly used as first-line for inpatient treatment of non-severe CAP(Metlay, 2019). In a community hospital, a CAP protocol was implemented to grant pharmacists the capability to discontinue antibiotics, including ceftriaxone, after 5 days of treatment in hospitalized patients that have reached clinical stability. On the other hand, extended treatment duration of ceftriaxone can lead to increased resistance, Clostridium difficile infections, adverse effects and cost (Guo 2017, Thomas 2002). The objective of this study is to compare patient outcomes between patients using ≤5 days (recommended duration) and >5 days (extended duration) of ceftriaxone.

Methods

This study is a retrospective chart review in a community hospital, from Nov 1, 2022 to April 30, 2023. Adult patients treated with ceftriaxone for ≥ 3 days for CAP were included. Patients treated for non-pulmonary infections and/or co-infections were excluded. The primary outcome of this study is 30-day mortality; secondary outcomes include length of stay, and Clostridium difficile infection within 90 days. Outcomes were analyzed with Chi-square/Fischer’s exact test, normality test, student t-test, and Mann-Whitney U test using Prism Version 10. IRB Number: 2024-167 AHGL

Results

The 30-day all-cause mortality was 7.1% for the ≤5 days group (N = 379) and 7.8% for the >5 days group (N = 166) was not statistically significant (p = 0.77). Length of stay median with interquartile range (IQR) was 6 (IQR 4-9) for the ≤5 days group and 8 (IQR 6-11) for the >5 days group (p < 0.01). The Clostridium difficile infection prevalence of 0.5% in the ≤5 days group and 0% in the >5 days group was too low to make any relevant analysis.

Conclusion

This study comparing patient outcomes between ≤5 days and >5 days durations of ceftriaxone for community-acquired pneumonia (CAP) revealed no significant difference in 30-day all-cause mortality rates but a significantly shorter hospital stays in ≤5 days group, which suggests that shorter ceftriaxone durations as per protocol can potentially optimize patient care by reducing hospital stays without compromising mortality outcome.

Disclosures

All Authors: No reported disclosures
P-756. Primary Mycobacterium Infections presenting in patients of Rheumatic diseases - A Case Series
Authors: Shah Aalesh , Patel Yug , Shukla Dhaiwat
Published: January 2025

Background

We present a study about patients with rheumatic diseases who were diagnosed for mycobacterium infections in their follow-up visit. The role of side effects of immunosuppressants have been established. However, their association with mycobacteria in endemic countries like India is yet to be understood well.

ABDOMINAL CT - CASE 1 (TUBERCULAR PERITONITIS)

Moderate to gross ascites with thickened enhancing parietal peritoneum, significant with caking and abdominal lymphadenopathy hence pointing towards Tubercular Peritonitis.

Methods

Consent was obtained from the patients to use their data for a case series. Relevant data related to the cases was collected, and organised.

HRCT THORX - CASE 3 (PULMONARY TB)

HRCT THORAX shows multiple, discrete, randomly distributed nodules in both the lungs, multiple enlarged lymph nodes in left axilla and in left anterior chest wall, some of which are confluent in nature and two calcifications in one of the lymph node.

Results

First case is about a 54 yr-old male patient, known case of Ankylosing spondylitis treated with 9 doses of Anti-TNF alpha drug Adalimumab presented with severe abdominal pain, fever with chills, vomiting & diarrhea for which he underwent abdominal CT-scan which revealed thickened enhancing parietal peritoneum, significant with caking and abdominal lymphadenopathy hence pointing towards Tubercular Peritonitis. Second case is about Non-Tuberculous Mycobacteria(NTM) or atypical mycobacteria diagnosed in a patient with Ankylosing Spondylitis who had negative tests for primary TB. Third case about a 28 year-old female, known case of bilateral iridocyclitis and recurrent multiple medium-vessel vasculitic/throm2botic occlusions treated with mycophenolate-mofetil and cyclosporine-A, was started on adalimumab. Later she presented with fever for which pulmonary workup was done which revealed positive TB. Fourth case is of a patient having symptoms similar to Rheumatoid arthritis but not responsive to treatment which led to extensive workup and mycobacterium leprae was found as a culprit. Fifth case is of a 16 year-old male, known case of GPA who was refractory to cyclophosphamide was started on rituximab, after which he presented with complaints of fever with chills and rigors, and breathlessness on exertion which was followed by the diagnosis of miliary tuberculosis.

TB patients were given Anti-tubercular therapy(ATT) and Leprosy patient was given Multi-drug therapy(MDT) and all are now improving.

Leonine Facies - Case 4

Conclusion

• Our study shows that immunosuppressants can be considered to have even increased risk of primary mycobacterium infection.

• Leprosy can present with similar manifestations of RA (Rheumatoid Arthritis) so signs of suspicion need to be kept in mind and screening should be done in such cases.

Leprosy mimicking RA - Case 4

Disclosures

All Authors: No reported disclosures
P-761. Advancing TB Patient Care: Utilizing XPERT MTB/XDR for Additional Drug Resistance Detection in an Indian Tertiary Care Context
Authors: Reddy challa Haripriya , Ventrapragada Bhuvaneswari , Mittal Ankit , Harshith B
Published: January 2025

Background

The World Health Organization (WHO) underscores the importance of universal access to drug susceptibility testing (DST) as a part of its END TB strategy. Rapid molecular tests with shorter turnaround time (TAT) are indispensable in this endeavor. Xpert MTB/XDR is one such test which identifies Mycobacterium tuberculosis complex (MTBC) and resistance to isoniazid, fluoroquinolones, aminoglycosides, and ethionamide. In this study we looked at clinical utility of this test in real world

Methods

Data of patients on whom Xpert MTB/XDR was done from September 2022 to April 2024 was collected retrospectively and analysed to see additional drug resistance capture. For baseline drug resistance data, we collected data of patients before September 2022 on whom additional DST (other than Rifampicin resistance testing by GeneXpert), including Line Probe Assays (LPA) and phenotypic DST (pDST) on culture isolates was done.

Results

Baseline drug susceptibility data were available for 39 patients, comprising 19 patients with first-line LPA, 14 with both first and second-line LPA, and 15 with only pDST. Among them, 3/39(7.69) exhibited rifampicin resistance, 7/39 (17.9) isoniazid resistance, 3/39(7.69) quinolone resistance, and 4/39(10.2) aminoglycoside resistance. Xpert MTB/XDR was performed on 193 patients, with 161 testing positive for MTBC. The median age of the study population was 64.5 years (IQR 29.7-56), with 64.7% being male. Rifampicin resistance was detected in 18/161 (11.18%) cases, isoniazid resistance in 24/161 (14.9%), fluoroquinolone resistance in 23/161 (14.29%), and aminoglycoside resistance in 4/161 (2.4%).Among all Rifampicin resistance patients 94% (14/18) are quinolone resistance. Isoniazid monoresistance is only 3% (5/161).

Conclusion

In clinical practice, compliance to FL-LPA, SL-LPA and pDST is low because of higher cost and TAT effecting capture of additional drug resistance especially of quinolones, which is an integral part of the drug resistant TB regimen. This is also important in special population like chronic liver disease or drug induced liver injury where pyrazinamide is replaced by quinolones. Xpert MTB/XDR is an efficient and cost-effective alternative to traditional DST methods with a lower TAT and should be integrated in National TB program

Disclosures

All Authors: No reported disclosures
P-775. Unlocking Synergistic Potency: Dual Action of β-Lactam and β-Lactamase Inhibitor in Combating Mycobacterium abscessus through β-Lactamase Inhibition and Multi-Target Receptor Inactivation
Authors: Shin Eunjeong , Dousa Khalid M , Bethel Christopher , Nantongo Mary , Holland Steven M , Rubin Eric , Bulitta Jürgen B , Kreiswirth Barry N , Bonomo Robert A
Published: January 2025

Background

Mycobacterium abscessus (Mab) poses significant clinical challenges, leading to chronic pulmonary disease in immunocompromised patients. Current treatment involve amikacin (AMK), which is toxic, highlighting the imperative for safer options. This study continues our evaluation of the synergistic effects of a β-lactam and β-lactamase inhibitor (BL/BLI) against Mab and to elucidate the underlying mechanism.

The inhibition constant (Ki,app)

Methods

The binding affinities and chemical interactions between target receptors (LDT1-5, DDC, PBP B, and PBP-lipo) and BL/BLI were determined via kinetics, mass spectrometry, DSF, flow cytometry and microscopy. The synergistic effects of BL/BLI were evaluated in time-kill studies, conducted over 10 days, using ATCC 19977 producing BlaMab.

Time-kill curves of monotherapy or double β-lactams (A, D, and G) and their combinations with avibactam (B, E, and H) or durlobactam+sulbactam (C, F, and I).

Results

Imipenem (IPM) showed high binding affinities for both LDTs and PBPs, with an extremely low inhibition constant (Ki,app; Tab. 1). Cephalosporins exhibited moderate binding affinity for both LDTs and PBPs, whereas amoxicillin (AMX) selectively targeted PBPs. The inactivation of BlaMab and LDTs/PBPs by durlobactam (DUR) exhibited greater efficacy compared to avibactam (AVI), aligning with their respective bactericidal effects. DUR showed a 75-fold lower Ki,app for BlaMab in comparison to AVI. The Ki,app of DUR for PBP B, PBP-lipo, and LDT2 fell below the clinical concentration, whereas those of AVI did not. Single β-lactam treatment resulted in minimal killing (∼1 log10 reduction), but adding AVI significantly enhanced killing by inhibition of β-lactamase (∼4 log10 reduction for IPM+AVI and ∼2 log10 reduction for others; Fig. 1). DUR alone showed 2 log10 reduction, and when combined with IPM or dual BL, it achieved near-eradication, surpassing the SOC (AMK + Clarithromycin + IPM or cefoxitin). Inhibition of PBP-lipo by sulopenem, IPM, DUR, and AMX changed the cell morphology to filaments. In accordance with the binding affinity to LDTs and PBPs, alterations in melting temperature were detected.

Conclusion

IPM + DUR + SUL showed the most killing of Mab with limited regrowth. This outcome can be attributed to β-lactamase inhibition and the inactivation of multiple targets, not only LDTs but also PBPs. This combination strategy holds promise for enhanced efficacy of Mab treatment, necessitating further study in clinical trials.

Disclosures

All Authors: No reported disclosures
P-778. Antimicrobial Effect of Nitric Oxide on Cystic Fibrosis Pathogens
Authors: Gibson Joy E , Youssef Christopher I , Neely Michael N
Published: January 2025

Background

Despite highly effective modulator therapy, bacterial pathogens persist in the airways of children and adults with CF. Staphylococcus aureus (Sa) and Pseudomonas aeruginosa (Pa) are most commonly identified, but others like Mycobacterium abscessus complex (MABSC) and Burkholderia cepacia complex (Bcc) are particularly challenging due to the high frequency of intrinsic and acquired antibiotic resistance. Treatment options for MABSC are limited, requiring prolonged exposure to multiple antibiotics that may cause significant toxicity and frequent failure. Novel treatment approaches are a high priority for management of infections in people with CF. One potential adjunctive therapy is inhaled nitric oxide (NO), which is frequently used in ventilated patients and has been explored for treatment of several pulmonary infections, given its antimicrobial properties.

Methods

In this study, we compared NO response in Sa, Pa, MABSC, and Bcc. We used chemical donors of NO, DETA NONOate and PAPA NONOate, to provide continuous or intermittent exposure, respectively, and compared growth curves assessed by OD600 over 24 hours for Sa, Pa, and Bcc, and 7 days for MABSC. We also exposed MABSC to different concentrations and frequencies of DETA and PAPA NONOate to determine the pharmacodynamics of this effect. To better correlate with clinical use, we further compared growth inhibition with gaseous NO delivered at 160 ppm thrice daily.

Results

We found that treatment with NONOate resulted in near complete inhibition of growth in MABSC at all concentrations, dose-dependent inhibition of Pa and Bcc, with a more potent affect on Bcc growth, and minimal growth inhibition of Sa. We quantified the minimum inhibitory concentration (MIC) of DETA NONOate in MABSC to be 660 µM and found the effect of NO on MABSC to be time-dependent based on linear regression of delta CFU relative to time above MIC (R2 =0.848), peak to MIC (R2 =0.344), and area under the curve to MIC (R2 =0.745). Gaseous NO resulted in greater than 50% growth inhibition of MABSC, but no inhibition in Pa or Bcc.

Conclusion

These findings indicate that inhaled NO may be a promising adjunctive therapy for treatment of MABSC, but may be less effective against other CF pathogens.

Disclosures

All Authors: No reported disclosures
P-781. The Impact of Hepatitis B Virus Infection on the Management of Latent Tuberculosis Infection in Northern California, 2010-2022
Authors: Fink Julia R , Dong Zinnia , Murrill Matthew , Wong Robert J , Chitnis Amit S , Jaganath Devan , Tang Amy S
Published: January 2025

Background

Tuberculosis (TB) and hepatitis B virus (HBV) infection affect similar at-risk populations. However, there is limited data on how co-infection may influence clinicians’ decision to offer TB preventative treatment (TPT) over concern for hepatotoxicity. We compared TPT by HBV status, and determined factors associated with TPT initiation among HBV-infected persons at a community health center in Northern California serving a large non-U.S.-born Asian population.

Methods

We extracted electronic health record data for all persons aged ≥18 years old with latent TB infection (LTBI), defined by a positive tuberculin skin test or interferon-gamma release assay in the absence of a TB disease diagnosis from 2010-2022. HBV infection was defined by a single positive HBV DNA or HBV surface antigen assay. We conducted multivariate logistic regression to explore the impact of (a) HBV status and (b) clinical and demographic variables on TPT initiation. We also examined how these factors changed when Rifampin (RIF) usage for TPT increased at this community health center after 2014.

Results

A total of 11,711 persons had LTBI and 5,530 had HBV. Of all persons with LTBI, 833 (9.0%) of those tested for HBV had a co-infection including 41 (4.9%) on HBV antiviral treatment; while 34% of all HBV-infected persons screened for TB had LTBI. Adjusting for demographics and time period, TPT was significantly lower among those with co-infection than those without (43.5% versus 47.4%, adjusted Odds Ratio (aOR) 0.76, 95% Confidence Interval (CI) 0.66 – 0.88, p< 0.01). Among those with co-infection, increasing age (50-64, ≥65 years), and elevated alanine transaminase (ALT) levels were associated with decreased likelihood of TPT (Table 1). Treatment of co-infected individuals was significantly higher after 2014 when RIF prescribing increased (aOR 2.76, 95% CI 1.81-4.2); however, age over 65 was still associated with decreased TPT prescription (aOR 0.36, 95% 0.19 – 0.67, p < 0.01).

Conclusion

HBV-LTBI co-infection was associated with reduced odds of TPT. Increased use of Rifamycin based regimens and further guidance on TPT and monitoring of older individuals and persons with elevated ALT levels may be needed to improve TB prevention efforts among HBV-LTBI co-infected persons.

Disclosures

Robert J. Wong, MD, MS, Durect Corporation: Grant/Research Support|Exact Sciences: Grant/Research Support|Gilead Sciences: Grant/Research Support|Thera Technologies: Grant/Research Support
Gait Speed Modifies Efficacy of Home-Based Exercise for Falls in Older Adults with a Previous Fall: Secondary Analysis of a Randomized Controlled Trial
Authors: Rice Jordyn , Falck Ryan S , Davis Jennifer C , Hsu Chun Liang , Dian Larry , Madden Kenneth , Parmar Naaz , Cook Wendy L , Khan Karim M , Liu-Ambrose Teresa
Published: January 2025

Objective

Exercise is an evidence-based strategy for preventing falls. However, its efficacy may vary based on individual characteristics, like gait speed. The study examined whether baseline gait speed modified the effects of home-based exercise on subsequent falls among older adults.

Methods

This is a secondary analysis of a 12-month, randomized controlled trial in community-dwelling adults who were ≥ 70 years old and who had fallen within the previous 12 months. Participants were randomized to either 12 months of home-based exercise (n = 172) or standard of care (n = 172). This study examined intervention effects on fall rates at 6 and 12 months stratified by baseline gait speed (slow [<0.80 m/s] or normal [≥0.80 m/s]) using negative binomial regressions. Baseline gait speed was investigated as a potential modifier of the intervention effects on mobility and cognitive function using linear mixed modeling.

Results

At baseline, 134 participants had slow (exercise = 70; standard of care = 64) and 210 had normal (exercise = 102; standard of care = 108) gait speeds. For participants with slow gait speed, exercise reduced fall rates by 44% at 6 months (incidence rate ratio = 0.56; 95% CI = 0.33 to 0.95) but not at 12 months (incidence rate ratio = 0.63; 95% CI = 0.38 to 1.03) compared with standard of care; for participants with normal gait speed, there was no significant effect of exercise on fall rates at 6 or 12 months. Gait speed modified intervention effects; in the exercise group, participants with slow gait showed significant improvements in the Timed “Up & Go” Test at 6 months (estimated mean difference = −4.05; 95% CI = −6.82 to −1.27) and the Digit Symbol Substitution Test at 12 months (estimated mean difference = 2.51; 95% CI = 0.81 to 4.21).

Conclusion

Older adults with slow gait speed had a reduction in subsequent falls in response to exercise at 6 months. Gait speed modified the effects of exercise on mobility and cognition.

Impact

Older adults with slow gait speed may be a target population for exercise-based fall prevention.
Aphra Behn, Anne Wharton, and the Remaking of Rochester’s Reputation
Authors: Wright Gillian
Published: January 2025

Restoration scholarship has often assumed both that Aphra Behn and the Earl of Rochester were personally acquainted and that Rochester was an important influence on Behn’s writing. This article reassesses the evidence for a literary relationship between Behn and Rochester, most of which postdates Rochester’s death in 1680. Focusing in particular on two poems by Behn—‘To Mrs W.’, addressed to Rochester’s niece, Anne Wharton, and her elegy ‘On the Death of the late Earl of Rochester’—it argues that what may look like a literary relationship between Behn and Rochester is often and more importantly a connection between Behn and Wharton. Positing a late (1685) date for ‘On the Death of the late Earl of Rochester’, it reframes its likely role within Behn’s career, and links it with wider efforts led by Wharton to refashion Rochester’s reputation after his death. It also explores the implications of the Behn-Wharton-Rochester relationship for Behn’s self-curation as a poet in the mid-1680s, as well as for Wharton’s own poetic development and literary ambitions.
SPECIAL ISSUE INTRODUCTION The Many Faces of Habeas Corpus in the American West
Authors: Jagodinsky Katrina
Published: January 2025

This introduction to a special issue offers a broad outline of habeas corpus historiography and explains the historical significance of that legal mechanism for people throughout the American West. It also explains the links between the special issue’s three articles—by Katrina Jagodinsky, Matthew Villeneuve, and Cory James Young—about women’s resistance to gendered violence, Indigenous families challenging federal Indian boarding school confinement, and Black minors’ ongoing vulnerability to coercive labor in the late nineteenth century.
Tranexamic dosing for major joint arthroplasty in adult patients with chronic kidney disease: A pharmacokinetic study and new dosing regimen.
Authors: Yang Qi , He Jim , Peng H. Benson , Wen Binyu , Idestrup Christopher , Ravi Bheeshma , Murnaghan John , McCarron Aaron , Hadley Hana , Shin Hansoo , Kaustov Lilia , Wong Jeremy , Lin Yulia , Choi Stephen , Orser Beverley A. , Van der Vyver Martin , Safa Ben , Pang K. Sandy , Jerath Angela
Published: January 2025

Background:

Tranexamic acid is an anti-fibrinolytic agent routinely used during hip and knee joint replacement surgery to minimize bleeding. Chronic kidney disease is a common chronic health problem seen among adults requiring major arthroplasty surgery. Tranexamic acid is renally cleared and may accumulate in chronic kidney disease. Optimal tranexamic acid dosing and dose adjustment for chronic kidney disease patients needing major arthroplasty is unknown. The objective of this study was to serially measure plasma tranexamic acid concentrations in patients with varied kidney function undergoing hip or knee replacement surgery for population pharmacokinetic modelling and to guide new dosing recommendations.

Methods:

Prospective cohort study enrolled 21 adults undergoing hip or knee replacement surgery between June 2020 – September 2022. Based on estimated glomerular filtration rate (eGFR), patients were stratified into good (≥ 60 mL/min/1.73 m2) and poor (< 60 mL/min/1.73 m2) renal function. Serial blood samples were taken to measure plasma tranexamic acid concentration levels (primary outcome) after an intravenous tranexamic acid 20 mg/kg bolus dose post anesthesia induction. Secondary clinical outcomes included adverse events (thromboembolic events, seizures), red cell transfusion, mortality, length of hospital stay. Analyses used curve stripping and population pharmacokinetic modelling and simulation.

Results:

Plasma tranexamic acid concentration levels were higher in patients with poor renal function and clearance compared to good renal function. Population pharmacokinetic modelling tested various tranexamic acid bolus and maintenance infusion regimens. Simulations revealed single bolus tranexamic acid administration leads to rapid rise and decline in plasma concentrations. We identified that plasma tranexamic acid levels of 50-75 mg/L were maintained for approximately 4 hours using a tranexamic acid bolus infusion of 15 mg/kg over 15 min together with a maintenance infusion of 7.5 mg/kg/h or 5 mg/kg/h for 2 hours for the good and poor renal function groups, respectively. There was no difference in secondary outcomes.

Conclusion:

Using population pharmacokinetic modelling and simulation, we recommend a new dosing regimen to optimize the anti-fibrinolytic effect of tranexamic acid and avoid excessive dosing.