bluuebunny/crossref_metadata_2025_split huggingface dataset:
1259. Successful Inpatient Penicillin Delabeling in Minimal and Low Risk Penicillin Allergic Patients
Authors: Petrak Robert , Shankaran Shivanjali , Goldenberg Benjamin , Won Sarah Y , Herald Fischer , Fayyaz Anum , Hodgson Hayley A 
Published: November 2023

Abstract

Background
In the US, 10% of adults report a Penicillin (PCN) allergy but true IgE-mediated or serious reactions are rare. A PCN allergy label carries risk for harm including fewer first-line treatment options, increased antimicrobial resistance, toxicities, surgical site infections, and death. The objective of this study was to identify and safely remove penicillin allergy labels in eligible hospitalized patients.

Methods
Between June 2022 - February 2023, the Antimicrobial Stewardship team electronically identified hospitalized patients with documented PCN allergy admitted to adult internal medicine wards at Rush University Medical Center (RUMC), an academic hospital in Chicago, IL. Patients with possible minimal or low risk PCN allergy reactions via chart review were administered a standardized questionnaire, followed by triage into Minimal, Low, and Moderate Risk PCN allergy categories (Figure 1). Minimal Risk patients were delabeled by history alone, or per patient request, after amoxicillin challenge. Low risk patients were offered an amoxicillin challenge with a single 500mg oral dose. Moderate or high risk patients were excluded.
Penicillin Allergy Risk Stratification

Results
Of 47 interviewed patients, 31 patients (20 minimal and 11 low risk) were appropriate for delabeling. 27 of 31 (87%) were successfully delabeled via history or amoxicillin challenge; 4 were not delabeled, due to patient discomfort or early discharge. 14 of the 31 (45%) were delabeled based on history alone; all had tolerated amoxicillin before. 13 amoxicillin challenges were administered, 9 of 11 patients in low risk, 4 of 20 in minimal risk group per patient request. 100% of amoxicillin challenges were well tolerated and patients successfully delabeled. Only 1 patient was relabeled at a subsequent hospitalization.
Penicillin Delabeling Results

Conclusion
In this proof-of-concept intervention, patients with a minimal or low risk penicillin allergy were safely delabeled as inpatients by history or amoxicillin challenge. Expanding this to a larger scale on the inpatient and outpatient settings would enable more patients with PCN allergy to be delabeled, leading to use of standard of care antibiotics and improved outcomes.

Disclosures
All Authors: No reported disclosures
1370. Prevalence and predictors of post-covid-19 (long covid) in India
Authors: Kumar Vignesh , Koshy Jency Maria , Divyashree S , Narreddy Suneetha , Rupali Priscilla , Sathyendra Sowmya 
Published: November 2023

Abstract

Background
Long COVID is a condition that occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. This Indian study followed up patients after an episode of acute COVID-19 for 1 year after hospital discharge from different parts of India.

Methods
This was a multi-centric bi-directional study among patients with confirmed COVID-19 which assessed patients at different time points, i.e. 6 weeks, 3-6, 6-9 and 9-12 months. Patients aged ≥18 years with laboratory confirmed COVID-19, were recruited and followed up telephonically using standardized surveys for quality of life. Data on demographics, pre-existing co-morbidities, risk factors, signs and symptoms and hospital parameters during acute COVID-19 infection were noted. An effort was made to include people with different severity of COVID-19. Univariate and multivariate analysis were performed to determine predictors of long covid.

Results
A total of 315 patients were enrolled (Table 1). Of these, 59.4 were males and 40.6 were females. The mean age was 51.98 ± 14.619 years. At 6 weeks and 12 months, 16.5% and 24% reported continuing symptoms. While shortness of breath was common at each time point, persistent muscle pain and weakness waxed and waned (Figure 1). At 1 year of follow-up, 24% still reported at least 1 troubling symptom and 26% reported &gt; 1 symptom that affected their quality of life i.e., nearly 8% of patients experienced problems in doing their usual activities, 11.7 % were slightly anxious or depressed and few 3.5% experienced slight pain or discomfort. In the multivariable analyses, the severity of disease at baseline (OR 2.330, 95% CI 1.080-5.027) and higher education (OR 0.437, 95% CI 0.241-1.793) seemed to be associated with long COVID.
Demographic and clinical characteristics according to the Severity of COVID
Persisting symptoms of Long COVID

Conclusion
We found that long covid symptoms may be persistent, following an initial recovery from an acute COVID-19 and may also fluctuate or relapse over time. Since symptoms persist in at least 25% of patients for at least 1 year after discharge, we urgently need therapeutic interventions which can improve the quality of life in patients after an acute episode of COVID-19 infection.

Disclosures
All Authors: No reported disclosures
1490. Predictors of Early Mortality in HIV-associated Tuberculous Meningitis
Authors: Kagimu Enock , Bangdiwala Ananta , Kasibante John , Kabahubya Mable , Gakuru Jane , Timothy Mugabi , Namombwe Suzan , Kimuda Sarah , Kasozi Derrick , Rutakingirwa Morris K , Ssebambulidde Kenneth , Tugume Lillian , Nuwagira Edwin , Okurut Samuel , Nsangi Laura , Atukunda Mucunguzi , Ellis Jayne P , Williams Darlisha A , Musubire Abdu Kisekka , Boulware David R , Meya David , Bahr Nathan C , Cresswell Fiona V 
Published: November 2023

Abstract

Background
Tuberculous meningitis (TBM) mortality averages at 27% but may reach 70% in HIV co-infection. High MRC severity grade, lower cerebrospinal fluid (CSF) white blood cell count (WBC) count, low weight, low CD4 and low plasma sodium were linked to mortality in Vietnam. Prognostic factors in African adults with HIV-associated TBM are unknown. We sought to determine the baseline factors predictive of death in HIV-positive Ugandan adults with TBM.

Methods
We prospectively enrolled patients who received TBM treatment and were classified as definite, probable or possible TBM by the uniform case definition from January 2019 to March 2023 in two National Referral Hospitals in Uganda. Participants received standard quadruple TB and corticosteroid therapy. We assessed association between baseline clinical and CSF characteristics (WBC&lt; 5, 5-100, &gt;100 cells/µl), antiretroviral therapy (ART) status and 14-day mortality.

Results
In 261 participants, median age was 36 years, 46% were women, median CD4 count was 74 cells/µl. 27% had definite, 39% probable, and 34% possible TBM. 142 (54%) had baseline CSF WBC &lt; 5, 50 (19%) had 5-100, and 69 (27%) had &gt;100 cells/µl.
Overall, 14-day mortality was 25.9%. Mortality was 73.6% in participants with CSF WBC count &lt; 5, 7.5% in 5-100, and 18.9% in &gt;100 cells/µl, p=0.0012. Factors associated with 14-day mortality were MRC severity grade, CSF WBC, CSF opening pressure (OP), CSF protein and glucose, CD4 count. ART status did not influence survival. The hazard of 14-day mortality was 4 times as high for those with CSF WBC &lt; 5 cells/µl as for those with &gt;100 cells/ µl (95%CI 1.47-11.5, P=0.004). However, on adjustment for Glasgow Coma Scale (GCS), CSF OP, glucose, and CD4 count the association was less significant (aHR, 2.93, 0.82-10.4, P=0.13).

Conclusion
14-day mortality varied significantly by baseline CSF WBC group, being extremely high (73.6%) in those with a paucity of CSF inflammation (WBC &lt; 5 cells/µl). Those with intermediate inflammation (CSF WBC 5-100 cells/µl) had lowest mortality in-line with the damage response framework parabola. The association with acellular CSF and mortality was ameliorated by adjustment for CD4 count. CSF inflammation is at predictor of mortality in HIV-associated TBM and CSF WBC-directed corticosteroid therapy needs further exploration.

Disclosures
All Authors: No reported disclosures
1604. Predicted Uptake of Novel HIV Treatment Options in the United States
Authors: Russell Elizabeth S , Song Yan , Gao Yipeng , Signorovitch James 
Published: November 2023

Abstract

Background
People with HIV (PWH) require lifelong treatment to achieve and maintain viral suppression. The modality and frequency of dosing for chronic medications may impact adherence, quality of life, and effectiveness. Preference data reported by potential users can inform which products in development may be preferred among people with various characteristics and social determinants of health, and can inform development for which product may have the largest health impact if it were available on the market. This study used the preference results from a latent class analysis to model uptake by product of a potential future market of HIV treatment options.

Methods
Data from an online discrete choice survey among 829 US adult PWH about treatment modality (daily or weekly oral pills, 3- or 6-monthly injections by health care providers (HCP), or yearly implants) were used in a latent class model to estimate partworth utility of each product in the 4 identified classes of participants. Probabilities of product uptake were estimated based on partworth utility-predicted product use among study participants and weighted for the US population of PWH. Characteristics considered for weighting were those previously reported to be associated with HIV care and treatment outcomes; they were included in weighting if available data from representative national data sources were found through a targeted literature search.

Results
Preference data weighted for the US population of PWH predicts that if all 5 products were available, they would be used in following proportions: 23.8% yearly implants, 23.7% weekly oral pills, 23.6% 6-month HCP-injections, 18.4% daily oral pills, and 10.5% 3-month HCP-injections. Despite oversampling PWH who were &lt; 40 years old, people with a history of food insecurity, and transgender men (Table 1), the weighted model including the characteristics in Table 1 did not alter predicted uptake by more than 2% for any product compared with the unweighted data.

Conclusion
Based on stated preference survey results, if 5 product delivery options for HIV treatment were available, product use would be broadly distributed, with weekly oral pills, yearly implant, and 6-month HCP-injections used in a similar proportion.

Disclosures
Elizabeth S. Russell, PhD, Merck & Co. Inc: Employee Yan Song, PhD, Merck & Co., Inc.: Grant/Research Support Yipeng Gao, PhD, Merck and Co.: Grant/Research Support James Signorovitch, PhD, Merck & Co., Inc.: Grant/Research Support
2126. Safety, Tolerability, and Pharmacokinetics (PK) in Healthy Participants Following Single Dose Administration of Zosurabalpin, a Novel Pathogen-Specific Antibiotic for the Treatment of Serious Acinetobacter Infections
Authors: Guenther Andreas , Millar Laurie , Messer Amanda , Giraudon Mylène , Patel Katie , Deurloo Erik J , Lobritz Michael , Gloge Andreas 
Published: November 2023

Abstract

Background
Zosurabalpin is the first representative of a novel class of tethered macrocyclic peptide antibiotics active against Acinetobacter spp., including carbapenem-resistant acinetobacter baumannii-calcoaceticus (ABC) complex organisms. This presentation summarizes and discusses unpublished preliminary safety and PK data of zosurabalpin from two completed Phase 1 clinical trials.

Methods
The entry-into-human study (BP41732) was a double-blind, placebo-controlled, randomized, single-and multiple ascending dose study in healthy participants. In Part 1 (SAD) of Study BP41732, participants were randomized 3:1 to receive IV zosurabalpin or placebo in sequential single ascending dose cohorts. The mass balance study (BP43532) was a non-randomized, non-controlled, open-label, single IV dose study in healthy male participants.

Results
Across these studies, 64 healthy male and female participants received a single IV dose of zosurabalpin ranging from 10 mg to 2000 mg. Participants receiving zosurabalpin, did not show any clinically significant changes compared to placebo in laboratory values, ECGs or vital signs compared to placebo.
The most common treatment-related adverse events were infusion-related reactions (IRRs), (9/64). IRR occurrence appeared to be dose-dependent, and all IRRs were fully reversible and mostly of mild intensity (7 mild/ 2 moderate).
The observed plasma exposures (Cmax and AUCinf) of zosurabalpin increased approximately dose-proportionally up to 1000 mg, and more than dose-proportionally thereafter. Total [14C]-radioactivity was approximately equally excreted in urine and feces, with on average 52.6% and 48.0% of the administered dose recovered, respectively.

Conclusion
Single IV doses of 10 mg to 2000 mg zosurabalpin were safe and overall well tolerated, and displayed a well-behaved PK profile in healthy participants. These data support evaluation of repeat dose administration in healthy participants.

Disclosures
Andreas Guenther, PhD, ​F. Hoffmann-La Roche Ltd: Employee Amanda Messer, BPharm, Roche Products Ltd: Employee Mylène Giraudon, PharmD, F. Hoffmann-La Roche Ltd: Employee Katie Patel, MSc, Roche Products Limited: Employer|Roche Products Limited: Stocks/Bonds Erik J. Deurloo, MSc, F. Hoffmann-La Roche Ltd: Salary|F. Hoffmann-La Roche Ltd: Stocks/Bonds Michael Lobritz, MD, PhD, Roche: full time employee|Roche: full time employee
2131. Activity of the Novel Antibiotic Zosurabalpin (RG6006) against Clinical Acinetobacter Isolates from China
Authors: Hawser Stephen , Kothari Nimmi , Valmont Thomas , Louvel Séverine , Zampaloni Claudia 
Published: November 2023

Abstract

Background
Zosurabalpin (RG6006) is the first representative of a novel class of tethered macrocyclic peptide antibiotics active against Acinetobacter spp., including carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) organisms. In this study, the susceptibility testing of zosurabalpin was carried out against a panel of 150 randomly selected Acinetobacter spp. isolates (100 A. baumannii & 50 non-A. baumannii) representing 11 sites in China and a broad susceptibility profile (65% of which were multi-drug resistant [MDR]) collected in 2021.

Methods
MICs were performed using the Clinical Laboratory Standards Institute (CLSI) broth dilution method cation-adjusted Mueller Hinton broth (CA-MHB) supplemented with either 20% of human serum (HS) or 20% of horse serum (HoS). For a fraction of isolates (10-25%), MIC determination for zosurabalpin is affected by aberrant readings (trailing, multiple skipped wells) in CA-MHB. This effect complicates routine susceptibility testing. Supplementation of CAMHB with serum allows accurate MIC determinations without any major effects on the MIC distribution.

Results
Summary data from the study are shown in Table 1.
Zosurabalpin was active against all Acinetobacter spp., with an MIC50/90 of 0.12/0.5 μg/mL and 0.25/1 μg/mL in CA-MHB supplemented with HoS and HS, respectively (MIC range of 0.015/0.03 to 8 μg/mL). Against ABC isolates (n=133), the MIC50/90 for zosurabalpin was 0.12/0.25 μg/mL and 0.25/0.5 μg/mL, in HoS and HS, respectively (MIC range of 0.015/0.03 to 1 μg/mL). A similar activity was observed against carbapenem-resistant ABC isolates.

Conclusion
In addition to the potent activity observed against isolates from USA and Europe, zosurabalpin exhibited potent in vitro antibacterial activity against Acinetobacter clinical isolates circulating in China. These data support the continued clinical development of zosurabalpin for infections caused by ABC isolates, including difficult to treat carbapenem-resistant isolates.

Disclosures
Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Thomas Valmont, BS, Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Séverine Louvel, PhD, F. Hoffmann-La Roche Ltd: employee of the company Claudia Zampaloni, n/a, F. Hoffmann-La Roche Ltd.: Full time employee of Roche
2941. Racial and Ethnic Disparities in the Care Cascade for Children with Perinatal Hepatitis C Virus (HCV) infection in the United States (US)
Authors: Rose Curtis Megan , Buzzee Ben , Biondi Breanne E , Linas Benjamin P , Ciaranello Andrea L , Epstein Rachel L 
Published: November 2023

Abstract

Background
From 2000-2019 HCV prevalence among pregnant people increased 10-fold in the US, in parallel to the opioid epidemic, with consequences for children, for whom perinatal transmission is the most common route of infection. Direct-acting antivirals (DAAs) were first approved for children ≥3 years old in 2019. The aim of this study was to characterize the care cascade among children with perinatal HCV and to examine racial and ethnic disparities in access to HCV care.

Methods
Analyzing 2014-2022 data from TriNetX, a research network of electronic health record data including 90 million individuals within US healthcare organizations, we defined a cohort of children born between 2010-2019 with a positive HCV ribonucleic acid (RNA) test. We defined linkage as: 1) HCV genotype test, 2) encounter with HCV as primary diagnosis, or 3) liver fibrosis testing. We tabulated the number of children prescribed DAAs and tested for sustained virologic response 12 weeks post-treatment (SVR12). We used logistic regression models to estimate odds of linkage and of receiving DAAs across racial and ethnic groups.

Results
Among 766 HCV RNA positive children, 211 (28%) linked to care. Only 40 children (5%; 19% of those linked) were prescribed DAAs and 15 (38% of those treated) had SVR12 assessed, all of whom achieved cure. Black and Hispanic children had 62% and 70% odds of linking (OR 0.38, 95%CI 0.19-0.76 and OR 0.30, 95%CI 0.18-0.51) when compared to White and non-Hispanic and children, respectively. Hispanic children had 72% lower odds of receiving DAAs compared with non-Hispanic children (OR 0.28, 95%CI 0.08-0.94). Disparities persisted for linkage when adjusted by region for Black and Hispanic children (OR 0.38, 95% CI 0.19-0.78 and OR 0.34, 95% CI 0.20-0.59) when compared to White and non-Hispanic children, respectively.

Conclusion
Despite DAA approvals for children ≥3 years old, most children with HCV are not yet linked or treated. This is a missed opportunity to prevent later health complications. Our study is the first to characterize the HCV care cascade in a large national cohort of children eligible for DAAs. We reveal major disparities in HCV care access for children, highlighting how infectious complications of the opioid epidemic might drive intergenerational disparities in health.

Disclosures
All Authors: No reported disclosures
2180. Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant
Authors: Zurita Jeannete , Sevillano Gabriela , Solis Maria Belen , Miño Ariane Paz y , Alves Beatriz Rizkallah 
Published: November 2023

Abstract

Background
Pseudomonas aeruginosa (PAE) is an opportunistic pathogen associated with a variety of hospital infections. Treatment of infections caused by PAE is challenging due to the emergence of multidrug-resistant (MDR), which is associated with increased morbidity, mortality, and healthcare costs. Clonal spread and the presence of resistance genes probably explain the successful propagation of MDR. In Ecuador, data on the molecular epidemiology, as well as circulating clones, are limited. Therefore, the objective of this study is to know the population structure of PAE by identifying clones in clinical samples in Quito-Ecuador.

Methods
A significant set (45) of randomly selected clinical PAE isolates, including multidrug and non-multidrug resistant isolates, were assigned to sequence types (STs) and compared them with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme (Figure 1) and the genetic relationships between different STs were corroborated by the phylogenetic neighbor-net network (Figure 2).Figure 1.Analysis of the allelic profiles using eBURST algorithm.Figure 2.Splits Tree showing the distribution of all the sequence types obtained for the clinical Pseudomonas aeruginosa isolates studied. The Splits Tree was based on the analysis of the allelic profiles of the acsA, aroE, guaA, mutL, nuoD, ppsA and trpE genes. Asterisk mark (*) indicates the MDR isolates

Results
The analysis of seven loci, acsA, aroE, guaA, mutL, nuoD, ppsA and trpE, identified 24 different ST and the most prevalent STs were ST-3750 and ST-253. A SplitsTree was constructed with all the isolates analyzed. The majority of the MDR isolates were included in ST-3750 and ST-253, also 3 singleton ST was identified in to MDR isolates. The 20 different ST was found to non-MDR isolates, and only 3 ST were found in more the one isolates.

Conclusion
The population structure of clinical PAE presents in these isolates indicate a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is closely related strains to the ST111 (CC111), and ST-253 and ST111 are a group of successful high-risk clones and widely distributed worldwide. The multiresistant-isolates studied are grouped in the most prevalent sequence types found, and the susceptible isolates correspond mainly to singleton sequence types. Therefore, these high-risk clones and their association with multidrug resistance phenotypes are contributing to the spread of MDR in Quito-Ecuador.

Disclosures
Jeannete Zurita, n/a, Pfizer: Grant/Research Support