bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1740. Impact of a System Wide Antimicrobial Stewardship Intervention Bundle to Improve Guideline Directed Antibiotics for Urinary Tract Infections
Authors: Weslander Erin , Borkowski Jaime , Moore William Justin , Bertram Christie M , Rhodes Nathaniel J , Chang Stephanie , Shah Rishita , Oliver Aaron , Dickens Michael , Johnicker Kyle , Polisetty Radhika S , Park Jong , Sutton Sarah , Postelnick Michael
Published: January 2025

Background

Urinary tract infections (UTIs) are one of the common reasons for antibiotic use across healthcare settings. Across an eleven-hospital system, common urinary pathogens (E. coli, Proteus species, and Klebsiella species) had greater than 80% coverage with cefazolin, which was within 0-8% of ceftriaxone coverage based on the local antibiograms. With increased risk of C. difficile infection and resistance development seen with ceftriaxone, cefazolin was promoted as first line for empiric UTI coverage.Table 1:Outcomes

Methods

An interrupted time series analysis was performed comparing a pre-intervention group to two phases of stewardship intervention (figure 1). The first intervention included an updated guideline, education, and pharmacist intervention upon order verification recommending guideline directed therapy. Guideline directed options and guideline non-compliant options are highlighted on green and red respectively, on figure 3. The second intervention was cascade reporting (figure 2) for urine culture Enterobacterales susceptibility, which was implemented across sites between 9/2023-1/2024. A generalized linear model with Poisson link was fit to the data. Compliant orders were regressed vs. the denominator of all UTI orders. Multiple models were considered, and the final model selection was based on likelihood ratio testing and the rule of parsimony.Figure 1:Interrupted Time-SeriesWhite = pre-intervention; light gray = intervention 1; dark gray = intervention 2

Results

In the four pre-intervention months, guideline compliance across the system was 38.1% (1674/4393), compared to 61.9% (6749/10,903) after intervention 1 was implemented (table 1). The final model suggested that intervention 1 was associated with a nearly 1.5-fold increase in compliance which was sustained over time and suggested that the compliance rate over time increased modestly at around 5% per quarter (figure 1). There was no change in length of stay, risk adjusted length of stay, or 30-day all-cause readmission (table 1).Figure 2:Microbiology Cascade Reporting Workflow

Conclusion

Guideline update, education, and frontline pharmacist intervention were significantly impactful in improving guideline directed treatment for UTIs. Cascade reporting on urine cultures may help reinforce guideline directed therapy but did not result in substantially different compliance rates from education with frontline pharmacist intervention.Figure 3:Percent of Patients with Empiric Guideline Directed Therapy Orders

Disclosures

Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant
P-1742. Isavuconazole Therapeutic Drug Monitoring and Association with Adverse Events
Authors: Huang Emily , Wittenberg Rebecca , Dray Joy Vongspanich , Thompson George R , Fine Jeffrey , Wilson Machelle , Chee Melissa
Published: January 2025

Background

Therapeutic drug monitoring (TDM) is often recommended with triazole antifungals. Isavuconazole TDM is currently not uniformly recommended due to its high oral bioavailability, modest drug-drug interactions, and linear pharmacokinetics; however, an assessment of serum levels and toxicity has not been reported.

This study aimed to explore the exposure-toxicity relationship for isavuconazole. The primary outcome was the threshold isavuconazole serum level most predictive of toxicity. Secondary outcomes included percentage of patients who developed adverse events and identification of adverse event profile.Table 1:Isavuconazole Adverse Event BreakdownThis table details the exact number and percentage of patients who experienced each type of adverse event reported by the patient sample with isavuconazole

Methods

This retrospective study analyzed adult patients who received oral isavuconazole and collected isavuconazole serum levels at our institution from 1/1/2015 to 10/4/2023. T-test and Fischer’s exact test were used to compare patients with and without adverse events, while Youdin’s index was used to identify a serum level most predictive of toxicity.

Results

Ninety-five patients, corresponding to 219 serum levels total (UPLC/MS), were analyzed. Thirty-seven patients (38.9%) developed adverse events, most commonly transaminitis (29.7%), diarrhea (24.3%), and nausea (18.9%) (Table 1). According to Youdin’s index, a serum level of 5.86 mcg/mL corresponded to a threshold that balances sensitivity and specificity for determining the risk of adverse events. Per multivariable logistic regression analysis, each one-unit increase (mcg/mL) in serum level was associated with a significantly increased odds risk of developing toxicity by 26%. All 24 patients who had isavuconazole dose-reduction secondary to adverse events demonstrated resolution of symptoms. Fifteen out of those 24 patients rechecked serum levels following dose reduction, yielding a mean serum level of 3.3 mcg/mL post-reduction, compared to 6.3 mcg/mL pre-reduction.

Conclusion

Our findings identify an exposure-toxicity relationship for isavuconazole. TDM may be beneficial for those on long-term isavuconazole therapy, especially in those who develop toxicity. Additionally, in patients with serum levels above 5.86 mcg/mL who show intolerable symptoms consistent with possible adverse drug effects, dose reduction is recommended.

Disclosures

George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant
P-1758. Evaluation of Real-Life Application of Multi-plex PCR Pneumonia Film-array Panel as an Antibiotic Stewardship Tool, a Prospective Investigation
Authors: Maryam Hera , Kim Brian , Arab Niki , Freites Christian Olivo , Furukawa Daisuke , Gallardo-Huizar Oscar , Huang Glen , Jeng Arthur
Published: January 2025

Background

Selecting empiric antibiotics (abx) for community-acquired and hospital-acquired pneumonia (CAP, HAP) on admission can be challenging, given the variety of possible pathogens. Per IDSA guidelines, broad spectrum antibiotic(s) are recommended, based on pneumonia type, risk of prior abx exposure/drug resistance, and disease severity. In this study, by using the BioFire® multi-plex PCR film-array (FA) on sputa, we prospectively investigated the time to pathogen identification in CAP and HAP, time to providing optimal abx, and types of change this strategy allowed.

Methods

Single center, prospective, observational study from January 1, 2021 to January 31, 2024. All admitted patients with CAP or HAP, with satisfactory sputa or bronchioalveolar lavage (BAL) cultures, were considered for inclusion by the Antimicrobial Stewardship service (ASP), whereby FA was performed on the sample. Exclusion criteria consisted of poor sample (≥ 10 epithelial cells/lpf), sputa previously ordered within 7 days, concurrent non-pneumonia infections and non-infectious pulmonary conditions. FA results and its respective abx recommendations were communicated to the patient’s clinician by ASP.

Results

148 samples met study criteria (Table 1). FA detected bacterial pathogens in 65% (n=96) and viruses in 16% (n=23) (Table 2). FA resulted in 2.9 hours (H) [IQR 1.75-2.87] after gram stain, whereas time to culture finalization was 90.5 H [IQR 45-82] (Figure 1). An average of 2 empiric abx days were saved per case [IQR 1-2]. Time to first modification of abx was 6.1 H [IQR 0.15-2.9]. 84% of abx courses were modified due to ASP intervention from FA, of which 86% resulted in de-escalation of empiric abx (Figure 2). 62% (n=92) had no growth on culture, and of those cases, 48% (n=44) had pathogen detected by FA. 50% (n=74) of bacterial culture results were congruent to FA, 19% (n=28) were partially congruent, with more bacteria detected on FA than culture.

Timeline

Conclusion

FA reduced time to pathogen identification compared to traditional culture in CAP and HAP, allowing ASP to provide rapid interventions to optimize abx treatment and save days of less optimal empiric abx. FA detected more pathogens compared to culture, including when negative, leading to abx changes in majority of cases. FA serves as a valuable tool for ASP.

Type of Intervention

Disclosures

All Authors: No reported disclosures
P-1829. Genomic Characterization of Clinically Significant Isolates and Its Effects on Clinical Outcomes, 2022 to 2024
Authors: Contreras Deisy , Grein Jonathan , Morgan Margie A
Published: January 2025

Background

Antimicrobial resistance has evolved into a complex global issue involving many clinically relevant organisms. Among these pathogens, carbapenem-resistant organisms (CROs) are of particular concern due to their limited treatment options and high mortality rates. In collaboration with Solu, whole-genome sequencing (WGS) was performed on clinical isolates recovered from our patient population to gain a better insight into resistance mechanisms present and their direct effect on clinical outcomes.

Methods

For genomic characterization (WGS), a total of 109 carbapenem resistant isolates across three clinically relevant bacterial groups (Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii complex) were sequenced. Solu utilized a hybrid assembly approach utilizing both long reads generated with Oxford Nanopore Technologies (ONT) complemented by Illumina short reads for the reconstruction of bacterial genomes.

Results

Multilocus sequence typing (MLST) revealed genetic diversity among all three groups of bacterial isolates. Among members of the family Enterobacterales, there were eight distinct sequence types: ST-131, ST-1431, ST-167, ST-2155, ST-361, ST-410, ST-685 and ST-405. A. baumannii complex strains mostly comprised of ST-2 and ST-1022. The presence of numerous sequence types was observed with the P. aeruginosa isolates, highlighting the biocomplexity within our patient population. Furthermore, genomic analysis of these isolates disclosed a broad range of antimicrobial resistance genes that span across several classes of antibiotics. Isolates across all genera harbored plasmid-mediated carbapenemase genes bla-NDM-5, bla-NDM1, bla-OXA-48 and bla-OXA23. Interestingly, cefiderocol resistance was primarily associated with the Escherichia coli ST-405 strain containing AMR gene bla-NDM5. Patients associated with a carbapenemase-producing strain were observed to have higher mortality rates (12.8%) and longer length of hospital stay (25.6%).

Conclusion

By having a comprehensive insight into the genomic composition of isolates that make up our patient population, we can provide a more targeted medical treatment approach and investigate and better prevent transmission events.

Disclosures

All Authors: No reported disclosures
P-1866. Polymorphonuclear Myeloid-Derived Suppressor Cells regulates immune reconstitution during HIV infection through PD-L1 and TGF-β signaling
Authors: Xia Huan
Published: January 2025

Background

Although myeloid-derived suppressor cells (MDSCs) are widely recognized for their immunoinhibitory effect in a variety of pathological conditions, their function during human immunodeficiency virus (HIV) infection and the onset of inadequate immune reconstitution remains elusive.

PMN-MDSCs inhibit autologous CD4+ T-cell proliferation and cytokines (IL-2, TNF-α, and IFN-γ) production in HIV INRs.

Methods

We conducted a cross-sectional study in which 30 healthy controls (HC) and 62 HIV-1-infected subjects [31 immunological non-responders (INRs) and 31 immunological responders (IRs)] were selected. After two years of antiretroviral therapy, INRs and IRs were designated as patients with CD4+ T-cell counts < 350 cells/μL and >500 cells/μL, respectively. The proportion of MDSCs was measured and their relationship with HIV disease progression was studied. Specifically, using flow cytometry and real-time PCR, immune regulatory molecules (including programmed death-ligand 1 [PD-L1], arginase 1, inducible nitric oxide synthase, interleukin 10, transforming growth factor beta [TGF-β], and indoleamine 2,3-dioxygenase) that are relevant for MDSCs activity were quantified. Furthermore, we investigated the impact of the blockade of PD-L1 and/or TGF-β signaling on MDSCs and their effects on CD4+ T cells using in vitro functional experiments.

PD-L1 and TGF-β mediate the suppressive effect of PMN-MDSCs on CD4+ T-cells response.

Results

We found that polymorphonuclear MDSCs (PMN-MDSCs) are more abundant and negatively correlated with CD4+ T-cell counts in HIV-infected individuals. PMN-MDSCs suppress CD4+ T-cell proliferation and interferon-γ (IFN-γ) production in INRs. Furthermore, correlations were found between PD-L1 expression on PMN-MDSCs and PD-1+ CD4+ T-cells. TGF-β expression on PMN-MDSCs was likewise enhanced in INRs. Importantly, inhibiting both PD-L1 and TGF-β signaling had a synergistic impact on restoring CD4+ T-cell activity in vitro.

Conclusion

Our findings reveal that the expansion of PMN-MDSCs decreased CD4+ T-cell proliferation and IFN-γ secretion in HIV infection through PD-L1 and TGF-β mediated pathways. Interventions that target both PD-L1 and TGF-β pathways may be novel strategies for enhancing immune reconstitution in INRs.

Disclosures

All Authors: No reported disclosures
638. Using NHSN Annual Self-Reported Dialysis Data to Understand Infection Prevention and Control Practices and their Association with Bloodstream Infections in Dialysis Facilities
Authors: Syed Rabia R , Pavlovsky Lacey , Tyner Kate , German Dan K , Cashatt Christina , Brailita Daniel M , Salman Ashraf Muhammad , Teran Plasencia Juan M
Published: January 2025

Background

Hemodialysis (HD) patients are at increased risk of bloodstream infection (BSI). Although BSI events are surveilled by the National Healthcare Safety Network (NHSN), studies correlating dialysis facilities’ self-reported infection control (IC) practices with BSI events are lacking.Figure 1.Seven Areas of Least Compliance by Facilities

A total of 34 facilities were included. Best practices were selected based on adherence by less than 2/3 of dialysis centers.

Methods

We used 2022 NHSN Annual Outpatient Dialysis Center Practices Survey data for Nebraska facilities to identify 44 questions pertaining to IC practices. These questions were included into a scoring system and dichotomized to adherent (1) or non-adherent (0), leading up to a “best practice (BP) score” for each facility. Questions related to attending IC training initiatives were coded as yes (1) or no (0). Self-reported adherence to CDC Dialysis Safety Core Interventions (DSCI) were coded as following all (1) or some/none (0). We extracted BSI standardized infection ratios (SIR) from NHSN Dialysis Events Surveillance data. Descriptive statistics was used to evaluate facility characteristics and scores. Multivariate regression, using a Poisson model, generated rate ratios (RR) to understand association of trainings/guidelines with BP scores and BSI SIR. Pearson correlation was used to assess association between BSI SIR and BP scores.Figure 2.BSI SIR and Overall Facility Performance Score Distributions

Results

A total of 34 facilities yielded a mean BP score of 36/44 (82%). The top 3 least reported BP strategies included: ointment application to HD catheter during dressing change (adhered by 2 of 34), medications drawn into syringes outside the patient room (adhered by 12 of 34), and patient education on showering with HD catheters (adhered by 15 of 34). Overall, facilities following all DSCI were associated with higher BP scores (RR: 1.11, 95% CI: 1.06, 1.16) and lower BSI SIR (RR: 0.33, 95% CI: 0.13, 0.83) compared to those who followed some or none. Similarly, facilities participating in infection prevention initiatives were associated with lower BSI SIR (RR: 0.39, 95% CI: 0.16, 0.96) compared to those who did not. An inverse association was found between BSI SIR and BP score (p=0.001).

Conclusion

Adherence to DSCI and participation in IC initiatives likely help HD facilities in preventing BSI events and need to be further explored. NHSN annual outpatient dialysis data provides important information about areas where further improvement is needed.

Disclosures

Muhammad Salman Ashraf, MBBS, Merck & Co. Inc: Grant/Research Support
P-1887. Outpatient vancomycin therapy: Rates of acute kidney injury in patients receiving area-under-the-curve-guided dosing as an inpatient followed by transition to trough-guided dosing after discharge
Authors: Honan Benjamin , Lim Lindsay , Hall Nicole M , Kim Janet , De Lima Daniela F
Published: January 2025

Background

Vancomycin is one of the most prescribed antibiotics for hospitalized patients. Targeting an area under the curve to a minimum inhibitory concentration (AUC/MIC) ratio of 400-600 mg*hour/L has been associated with a reduction in vancomycin-induced acute kidney injury (AKI) compared to trough-guided dosing. Data evaluating AUC-guided vancomycin dosing in outpatient parenteral antimicrobial therapy (OPAT) are limited, and resources required for AUC-guided dosing are often unavailable. However, trough-guided dosing has been associated with vancomycin overexposure and in the outpatient setting, rates of AKI as high as 28.5% have been reported. We aim to evaluate outcomes of patients discharged on at least one week of vancomycin on a dose established through AUC-guided dosing during hospitalization followed by trough-guided dosing in the outpatient setting.

Methods

In this retrospective single-center cohort study, we identified 120 patients admitted to the University of Alabama (UAB) Hospital or UAB Hospital-Highlands between October 1, 2021, and March 31, 2022, who met criteria for inclusion. Though we collected additional demographics and clinical information, our primary outcome was the development of AKI, as defined by the 2012 KDIGO guidelines, while receiving vancomycin via OPAT.

Results

Approximately 17% of patients developed an AKI using this hybrid model. The most treated infection was prosthetic joint or hardware-associated infections (40.8%), and the most targeted organism was MRSA (41.7%). Vancomycin monotherapy comprised almost half of the antibiotic regimens on discharge (48.3%); the second agent, if prescribed, was typically a beta-lactam other than piperacillin-tazobactam (36.7%).

Conclusion

Future directions include identifying predictors for the development of AKI while receiving vancomycin via OPAT and comparing outcomes of this hybrid model with a historical cohort of patients at our institution who received trough-guided dosing in both the inpatient and outpatient settings. Given the paucity of data on vancomycin dosing in the outpatient setting, investigating optimal and sustainable OPAT vancomycin dosing and monitoring is of the utmost importance to minimize adverse events and maximize patient safety.

Disclosures

All Authors: No reported disclosures
P-1888. Quantifying the Potential Impact of Dalbavancin on Health Care Metrics Associated with Outpatient Parenteral Antibiotic Therapy Management of Streptococcus and Staphylococcus Infections
Authors: Li Lucy X , Anderson Sean , Judson Seth , Visek Caitlin , Brenon Jessa , Wright William F , Keller Sara C
Published: January 2025

Background

Socially vulnerable patients often complete parenteral antibiotic courses in healthcare facilities due to injection drug use (IDU) history or unstable housing situations, which leads to significant personal and health system costs and prolonged hospitalization risks. Our aim was to assess the potential impact of dalbavancin (DBV) utilization on length of stay (LOS) and adverse outcomes in this patient population.

Methods

Retrospective study of patients ≥ 18 years old who were followed in the Johns Hopkins Health System Outpatient Parenteral Antibiotic Therapy (OPAT) program from 1/1/2021 to 6/30/2023 for Streptococcus and Staphylococcus bone/joint and endovascular infections (n = 900). Descriptive statistics were used to evaluate demographic, microbiologic, and clinical characteristics. Potential demand for DBV was quantified by estimating the impact of transitioning patients to DBV in terms of possible hospital days saved and OPAT-related complications avoided. Subanalyses were completed for patients with IDU history.

Results

Median patient age was 58 years (IQR 44-68 years) and 501/900 (56%) were male. Most patients received vancomycin (30%) followed by cefazolin (24.4%) or anti-staphylococcal penicillin (24.0%), which required central venous catheter placement in 86.6% of patients. The most common indication for OPAT was osteomyelitis (54.8%) followed by endovascular infection. The median LOS after finalization of antibiotic recommendations was 5 days (IQR 3-10 days) with 44.3% requiring skilled nursing facility (SNF) placement. 43.7% of patients experienced an OPAT-related adverse event, almost half of which involved a return to the hospital. Among OPAT patients, 16.4% had an IDU history and 75.8% of them injected within the last 6 months. These patients had longer LOS (8 vs 5 days) after finalization of antibiotic recommendations and more OPAT-related adverse events compared to patients without IDU history (48.0% vs 43.7%).

Conclusion

Patients, especially those with recent IDU, could benefit from DBV in lieu of parenteral antibiotics to complete prolonged treatment courses. Completion of deep-seeded gram-positive infection therapy with DBV vs OPAT has the potential to shorten hospital LOS and reduce the incidence of OPAT-associated adverse events.

Disclosures

All Authors: No reported disclosures
P-1892. Dabbling with Dalbavancin: Implementation and Cost-savings of an Inpatient-to-Outpatient Dalbavancin Pathway
Authors: O’Neal Melissa , Piccicacco Nicholas , Zeitler Kristen , Weber Jaimie , McConnell Douglas , Conn Chris , Carrieri Kari , Hall Susannah , Montero Jose
Published: January 2025

Background

Dalbavancin is a lipoglycopeptide antibiotic with in vitro activity against gram-positive organisms and a terminal half-life of 14.4 days. One dose provides 7 days of therapy whereas a novel 2-dose regimen provides up to 4-6 weeks. These strategies are attractive alternatives to standard of care for patients in whom daily IV antibiotics are not feasible. There also may be a financial benefit as the dosing schedule allows for completion of therapy in the outpatient setting and can reduce hospitalization costs.

Methods

This study is a retrospective chart review of all patients who received dalbavancin at Tampa General Hospital. Our institution approved the use of dalbavancin at no cost to patients for vancomycin-susceptible gram-positive infections who remain hospitalized only to receive IV antibiotics. All patients received at least one 1500mg dose inpatient to save 7 days of hospitalization; some patients planned to follow up a week later in an outpatient clinic for a second 1500mg dose to save at least 4 weeks of hospitalization. Cost estimates are based on the patient’s hospitalization cost prior to receiving dalbavancin and do not include avoided implicit costs.

Results

From 12/13/22 to 3/31/24, 28 patients received dalbavancin; 14 (50%) planned to receive a second dose and 11 (78.6%) successfully received their dose in clinic. The majority of patients (60.7%) reported a history of injection drug use. Most infections were monomicrobial (85.7%) with S. aureus being the most common pathogen. An estimated 527 days of hospitalization were avoided, representing a cost savings of $684,712.44. The institutional drug cost for dalbavancin was $104,772, leading to an estimated net hospital cost savings of $579,940.44. The all-cause 30-day readmission or revisit rate was 28.6%, similar to reported readmission rates in this population, however the 30-day infection-related readmission or revisit rate was favorable (10.7%).

Conclusion

The use of dalbavancin to facilitate discharge resulted in significant cost savings without increasing infection-related readmissions. Further cost-benefit analysis on true economic impact including the reduction in nosocomial infections and avoidance of toxicities is warranted.

Disclosures

All Authors: No reported disclosures
P-1893. Evaluation of Infectious Disease Consultation on Outpatient Antimicrobial Therapy (OPAT) Referral Volume and Outcomes
Authors: Slain Nicole , Mynatt Ryan P , Ruf Kathryn , Cari Evelyn Villacorta , Mansoor Armaghan-E Rehman , Burgess Donna R , Clemons Alisha , Logan Ashley
Published: January 2025

Background

Institutional experience with OPAT is increasingly reported. However, little is known about the referral process across the continuum of care and its impact on OPAT volume and patient outcomes. The purpose of this study is to characterize OPAT referral trends from a multi-service line infectious diseases (ID) group and its impact on end of therapy patient outcomes.

Methods

This retrospective analysis included adult patients referred to the OPAT program from either of the two system hospitals and seen by any of the five inpatient consult teams or the ambulatory ID clinic between June 2021 and July 2022. Patients were identified via a data extraction from the electronic health record by the institution’s Healthcare Analytics Team or Center for Clinical and Translational Sciences. OPAT patients were identified via the OPAT Electronic Data Capture (REDCap) database.

Results

A total of 3738 ID consult orders were placed on 2708 patients, dispersed between four consult teams at hospital 1 (Table 1). The OPAT program received 1504 referrals, 1475 (98.1%) inpatient referrals and 29 (1.9%) outpatient. A total of 914 patients were discharged to receive IV antimicrobials, 723 (78.2%) and 191 (32.9%) (p < 0.00001), for standard OPAT (S-OPAT) and modified OPAT (M-OPAT), respectively (Figure 1). End of therapy outcomes were recorded on 798 (87.3%) patients. The Transplant service had the highest percentage of referrals eligible for S-OPAT (90%); however, it also saw the highest 60-day readmission rate (36.2%) (Table 1). There was no statistically significant difference (p = 0.281) in proportion of referrals with end of treatment failure within the ID services at hospital 1. However, therapy extension was more frequent in the Bone and Joint and General ID teams (p < 0.001). Hospital 2 had more patients that were unable to complete their antimicrobial therapy (14.6%) (Table 3).

Conclusion

Our analysis of patients seen by ID consult services demonstrated a significant portion were ultimately referred for OPAT. Differences in referral rates were noted between service lines, along with differences in 30 and 60-day readmission rates. Overall, end of therapy and clinical outcomes were fairly similar throughout the groups.

Disclosures

Alisha Clemons, APRN, Gilead Sciences: Honoraria
P-1907. Comparing Multisystem Inflammatory Syndrome in Children (MIS-C) Case Characteristics Across Periods of SARS-CoV-2 (SC2) Variant Predominance in Los Angeles County (LAC): 2020-2023
Authors: Collins Christina , de St Maurice Annabelle , Traub Elizabeth , Khanqadri Israa , Finn Lauren E
Published: January 2025

Background

MIS-C is a rare condition in children associated with prior SC2 infection. Limited data show the impact of SC2 variants on the presentation of MIS-C. This study analyzes differences in the presentation of MIS-C cases in LAC when different variants were circulating.

Characteristics of Multisystem Inflammatory Syndrome in Children (MIS-C) Cases, -- Los Angeles County*, California March 1, 2020- December 31, 2023

Methods

This analysis includes MIS-C cases in people < 21 years of age reported to LAC with onset from 3/1/2020-12/31/2023. We defined confirmed SC2 infection as having a documented positive SC2 test with specimen collection date < 60 days prior to MIS-C symptom onset. Where SC2 positive results were not available, we imputed SC2 infection as occurring 30 days prior to MIS-C onset. Infection dates were used to classify cases by variant predominant periods, defined as weeks where > 50% of sequenced specimens reported to LAC were a particular variant as defined by the WHO as a variant of concern. Case demographics and clinical characteristics were compared across variant periods. Analyses were conducted for all reported MIS-C cases and for cases with confirmed SC2 infection. Statistical significance was tested with the Kruskal-Wallis test and chi-squared test [α=0.05].

Results

349 MIS-C cases were reported between 2020-2023 (Table 1). Of these, 102 (29.2%) had a documented SC2 infection. Median age at onset was 7.8 years. 168 (48.1%) had ≥ 1 comorbidity, 124 (35.5%) were admitted to the ICU, and median hospital length of stay (LOS) was 5 days. 18 cases were vaccinated prior to MIS-C onset. The most SC2 infections occurred during the Pre-Delta period (230, 65.9%), while the fewest occurred during the Delta period (57, 16.3%) (Table 2). Median age and proportion of children with ≥ 1 comorbidity decreased across variant periods (p < 0.0001, p=0.0102; respectively). The median LOS was lowest when SC2 infection occurred during the Omicron period (p=0.0370). ICU admission was not statistically different across variant periods.

Conclusion

The LOS, median age, and proportion of cases with comorbidities decreased when SC2 infection occurred during the Omicron period. This may be due to differences in variant pathogenicity, natural immunity decreasing the MIS-C susceptible pool, and younger children being the last group to be eligible for vaccination during later variant periods.

Disclosures

All Authors: No reported disclosures
P-1909. Social Connectedness in the COVID-19 Pandemic’s Aftermath: The Influence of Disease Status
Authors: Kricorian Christopher
Published: January 2025

Background

During the COVID-19 pandemic, maintaining social connectedness became difficult.As the pandemic receded, these challenges eased and allowed people to re-develop their social relationships. However, those with Long COVID (LC) may experience ongoing difficulties given the effects of their illness, but limited research has examined the association of LC with social connectedness.

Methods

The US Census Bureau Household Pulse Survey data was used in this analysis. Data was collected online between January 9 - February 5, 2024, in English and Spanish. Sample size was N=68,544. Social connectedness metrics were compared between those reporting LC, COVID-19 infection that had resolved (Short COVID, or SC), and those who had not experienced COVID (No COVID, or NC). Data were analyzed using χ2 and between group contrast analysis.

Results

When asked how often they feel lonely, those with LC were significantly more likely to say always, usually, or sometimes as compared to SC and NC respondents and less likely to say rarely or never (all comparisons to LC p< .05). In terms of receiving necessary social and emotional support, only 21.6% of those with LC said they always get necessary support, vs. 30.9% for SC and 30.0% for NC (both LC comparisons p< .05). LC respondents were most likely to say they got together with friends or relatives less than once per week (47.1%, vs. 35.3% SC and 43.1% NC, all comparisons p< .05). Those experiencing SC were most likely to say they texted with friends, family or neighbors 5+ times per week (70.1%), followed by LC (65.1%), then NC (59.9%, all comparisons p< .05).

Conclusion

People suffering from LC generally exhibited lower levels of social connectedness and had lower likelihood of obtaining necessary social and emotional support than those who experienced SC or NC. Additional research should be conducted to better understand the causal connections: are people with poorer social connections more likely to experience LC, does LC damage the ability to become or remain socially connected, or both? More research is needed to examine these questions and develop programs to help rebuild and retain social connections in the aftermath of the COVID-19 pandemic.

Disclosures

All Authors: No reported disclosures
P-1911. Covid-19 Associated Mucor-Aspergillosis Incidence, Management and Outcome analysis
Authors: Kola Venkat R
Published: January 2025

Background

The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis as well as mixed mucormycosis and aspergillosis in these patients is very much concerning. COVID19-associated Mucor-Aspergillosis was detected in significant numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucor-aspergillosis(CAMA).

Histopathology image showing aspergillosis and mucormycosis

Histopathology of CAMA

Methods

A multicenter ambispective study across three tertiary health care centers in Southern part of India was conducted during April-October 2021and the patients were followed up for a period of 30 months till April 2024.

Surgical Debridement specimen (Maxillectomy) of CAMA

Surgical Debridement specimen (Maxillectomy) of CAMA

Results

Among the 56 cases of CAMA, mucor-aspergillosis affecting the nasal sinuses was the commonest, affecting 29(51%) of the patients, orbital extension seen in 15(26%), pulmonary (n=8, 14%), gastrointestinal (n=2, 3%), isolated cerebral (n=1) and disseminated mucor-aspergillosis in 1 patient. Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAMA patients.

The CAMA associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucor-aspergillosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucor-aspergillosis patients.

Conclusion

The incidence of mucor-aspergillosis increased immensely during the second wave of COVID in India, and hence clinicians should be aware and have up-to-date knowledge of the predisposing factor, clinical signs and symptoms, diagnostic modalities and treatment strategies of the various types of CAMA. Also, the treating physicians should remember the predisposing factor involved in the development of CAMA, the improper use of glucocorticoid, and should manage COVID cases accordingly with the appropriate drugs, thus preventing increase in CAMA cases. Multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.

Disclosures

All Authors: No reported disclosures
P-1915. Factors Associated with Post-discharge Mortality among SARS-CoV-2-infected Adult Patients with Severe Acute Respiratory Infection in Bangladesh during 2020–2023
Authors: Bhuiya Saju , Islam Md Ariful , Shuvo Tanzir Ahmed , Abdul Aleem Md , Hassan Md Zakiul , Chowdhury Fahmida
Published: January 2025

Background

To better understand the true mortality burden among SARS-CoV-2-infected patients with severe respiratory illnesses, in resource-limited settings in Bangladesh, it is crucial to consider post-discharge deaths along with in-hospital deaths. We estimated the proportion of SARS-CoV-2-associated adult SARI patients who died after discharge and identified factors associated with these deaths.

Methods

From March 2020–December 2023, we analyzed WHO defined severe acute respiratory infection (SARI) patient data from nine tertiary-level hospitals participating in national hospital-based influenza surveillance in Bangladesh. We estimated the proportion of SARS-CoV-2-associated deaths that occurred within 30 days after hospital-discharge and compared demographics, clinical characteristics between SARS-CoV-2-associated decedents and SARS-CoV-2 survivors. Logistic regression analyses were performed to determine for factors associated with SARS-CoV-2-infected post-discharge deaths.

Results

We identified 7,816 SARI patients with a median age of 50 years (IQR: 32–60), 62% were male, and 16.4% (1,280) were laboratory-confirmed SARS-CoV-2-infected patients. Of the SARS-CoV-2-infected patients, 9.8% (126) died during their hospital stay. Of 1,154 patients who were alive at discharge, we followed 1,108 (96%) patients, and 111 (10%) died within 30 days after discharge. Patients aged 40-60 (aOR: 8.3, 95% CI: 2.45-27.70) and those aged ≥60 (aOR: 26.3, 95% CI: 8.01-86.2) compared to 18-40 years, residents of rural areas (aOR: 1.91, 95% CI: 1.10-3.31), and individuals with difficulty breathing (aOR: 4.13, 95% CI: 1.75-9.75) or kidney diseases (aOR: 4.62, 95% CI: 1.32-16.14) were significantly associated with a higher risk of post-discharge death.

Conclusion

Almost half of the deaths among SARS-CoV-2-infected SARI patients in Bangladesh occurred within 30 days post-discharge. To improve post-discharge recovery among vulnerable patients with potential risk attributes, hospitals in resource-limited settings could develop safe-discharge algorithms, strengthen post-discharge care plans, and establish outpatient monitoring of recently discharged patients.

Disclosures

All Authors: No reported disclosures
P-1945. Genomic Surveillance of SARS-CoV-2 Variants among Children Enrolled in the New Vaccine Surveillance Network (NVSN) - Kansas City
Authors: Banerjee Dithi , Gummersheimer Stephanie , Sasidharan Anjana , Clopper Benjamin R , Moline Heidi L , Selvarangan Rangaraj
Published: January 2025

Background

SARS-CoV-2 has evolved since its emergence in late December 2019, with evidence for increased contagiousness, evasion of immunity and missed detection by diagnostic assays. SARS-CoV-2 genomic surveillance in children is important to evaluate impact of the variants on pediatric COVID-19 disease.

Methods

During April 2021-October 2023, the New Vaccine Surveillance Network conducted active, prospective surveillance for acute respiratory illness (ARI) among children (< 18 years). Children with ARI symptoms were enrolled and had mid-turbinate swab samples tested for SARS-CoV-2, either by clinical standard of care or by surveillance testing. SARS-CoV-2 positive samples with cycle threshold values < 30 were processed using PacBio HiFiViral SARS-CoV-2 kit and sequenced on a Sequel IIe system. Consensus FASTA sequences were generated using SMRT® Link (V13.0); clades and lineages were assigned using Nextclade (https://clades.nextstrain.org/). Additionally, number of mapped reads, median coverage, list of S gene mutations, and multiple strains probability were determined.

Results

We attempted sequencing of 204 samples and sequenced 150 (73.5%) samples; 130/150 samples had >95% coverage. Sequencing failed in 52 (25.5%) samples (< 70% coverage) and 2 (0.9%) without any genome coverage. SMRT link analysis flagged 29 samples (14.2%) as having multiple strains (probability >0.95). Median genome coverage was 99.5% (IQR: 98–99.6], with a median of 12768 reads/ sample (IQR: 2913 - 50502). Twenty-eight Delta strains from 2 clades and 7 lineages (mostly clade 21J - 27, 18%) and 122 Omicron strains from 13 clades and 24 lineages (mostly clade 21K - 61, 40.7%) were identified. All identified strains had >1 S gene substitution, while 149 (99.3%) and 66 (44%) had S gene deletions and insertions, respectively. Delta variants were detected from September - December of 2021 with occasional detections after December 2021, while Omicron variants were detected from January 2022-October 2023.

Conclusion

Compared to Delta variants, Omicron variants were detected among children with medically attended ARI for a longer period and included more viral diversity. Continued monitoring of COVID-19 variants and their impact on pediatric illness is important.

Disclosures

Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, FAAM, Abbott: Grant/Research Support|Abbott: Honoraria|BioMerieux: Grant/Research Support|Cepheid: Grant/Research Support|Diasorin: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Luminex: Grant/Research Support|Qiagen: Grant/Research Support
P-1966. Depression and Anxiety Symptoms During COVID-19: Age-Related Advantages in Well-Being
Authors: Goh Nicole S E , Tan Sharon , Yap Alex , Lye David , Tan Kelvin Bryan
Published: January 2025

Background

The long-term effects of the COVID-19 pandemic on individuals’ physical and mental health are of widespread societal concern. However, in the sphere of mental health, little research has been done on the pandemic’s differential impacts on different sociodemographic groups over time.

Methods

This study evaluates anxiety and depression symptoms across different age groups in Singapore as pandemic restrictions were gradually lifted. Cross-sectional data was gathered in 36 waves through the Imperial College London-YouGov Covid-19 Behavioral Tracker. Results from 34429 adults in Singapore between 27 April 2020 and 27 September 2021 were analyzed. Multivariable logistic and linear regression were carried out to assess Patient Health Questionnaire-4 (PHQ-4) scores over pandemic phases and by age, adjusting for sex, employment status, availability of COVID-19 vaccine, and pre-existing mental health conditions.

Results

Overall depression and anxiety symptoms as measured by the PHQ-4 did not vary significantly across the pandemic. However, younger age groups reported higher PHQ-4 scores as restrictions lifted (ages 18-29: d=0.59, 95% CI [0.22, 0.97], p< 0.05; ages 30-39: d=0.43, 95% CI [0.07, 0.79], p< 0.05), while older adults reported lower scores over time (ages 50-59: d=-0.45, 95% CI [-0.80, -0.10, p< 0.05; ages 60 and above: d=-0.38, 95% CI [-0.74, -0.02], p< 0.05). This was driven by increases in symptoms of anxiety for younger adults and reductions in symptoms of both depression and anxiety for older adults.

Conclusion

Among Singaporean adults, age-related advantages are observed in psychological well-being. Population resilience to the pandemic may be heterogenous, with more intervention required to psychologically support younger adults.

Disclosures

All Authors: No reported disclosures
P-2018. Nirmatrelvir versus Short-Course Remdesivir for Mild-to-Moderate COVID-19 in High Risk Hospitalized Patients: A Propensity Score-Matched Study
Authors: Belk Madeline , Steuber Taylor , Edwards Jonathan
Published: January 2025

Background

As the Coronavirus disease 2019 (COVID-19) has evolved, patients often present with mild-to-moderate disease as opposed to severe disease that was seen earlier in the pandemic. Two previously published studies (PINETREE and EPIC-HR) evaluated treatment options in the outpatient setting for patients with mild-to-moderate disease. These studies may provide insight into how patients with similar disease presentation may be treated in the inpatient setting. The purpose of this study was to evaluate the use of nirmatrelvir (N/R) and short-course remdesivir in high-risk patients hospitalized with mild-to-moderate COVID-19.

Clinical Outcomes in the Propensity-Matched Cohort

Methods

This was a single-center, retrospective cohort study including adult patients hospitalized for mild-to-moderate COVID-19 between January 2021 and December 2023. Patients were grouped by treatment received (N/R or short-course [3-day] remdesivir). They were excluded if they received additional COVID-19 therapies, did not receive the appropriate regimen or were treated prior to hospitalization. Patients were compared by treatment received after propensity score-matching based on baseline characteristics. The primary endpoint assessed was the need for oxygen support. Exploratory endpoints included need for mechanical ventilation, length of stay, 30-day readmission, and mortality.

Results

Eight-hundred and fifty-six patients were initially screened. After exclusions and propensity score-matching, a total of 75 matched pairs (N=150) were included in the analysis. Patients had an average of three comorbidities or high risk features for COVID-19 progression, most commonly age greater than 60 years, BMI over 25 kg/m2, hypertension, and diabetes. There was no difference in the primary outcome of need for oxygen support in the short-course remdesivir group compared to the N/R group (14 [19%] vs 7 [9%], respectively; p=0.100). There was also no difference in length of stay between the two groups (5 [3, 7] vs 4 [2, 7] days, respectively; p=0.068). All additional endpoints were similar between short-course remdesivir and N/R.

Conclusion

Patients at high-risk of progression with mild-to-moderate COVID-19 that received N/R or short-course remdesivir had similar rates of disease progression, length of stay, readmissions, and mortality.

Disclosures

Jonathan Edwards, PharmD, BCPS, BCGP, BCIDP, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria
P-2040. Real-world safety and effectiveness of ensitrelvir in COVID-19 patients with risk factor : a post-marketing surveillance in Japan
Authors: Takashima Satoru , Hayashi Noriko , Tsukimura Eri , Ogura Eriko
Published: January 2025

Background

After obtaining emergency approval on November 22, 2022, a post-marketing surveillance (PMS) in COVID-19 patients was conducted in Japan to investigate the safety and effectiveness of ensitrelvir. We report the safety and effectiveness of ensitrelvir focusing on patients with high-risk (HR) factors for severe COVID-19.

Methods

In the PMS, COVID-19 patients administered ensitrelvir for the first time in about 500 Japanese hospitals or clinics were targeted and observed for 28 days after the first administration. Patient demographics, concomitant medications, other therapy for COVID-19, adverse events, and clinical course (fever, systemic, respiratory, and gastrointestinal symptoms) were investigated.

Results

A total of 4155 cases participated from November 2022 to August 2023, and 4125 case reports were collected. The safety and effectiveness analysis population were 3760 and 3638 cases respectively. Among the safety analysis population, the average age was 43.6 years; 452 cases (12.0%) were aged 65 and over; 1823 cases (48.5%) were male; and 939 cases (25.0%) had HR factors. The severity of COVID-19 was mild in 3666 cases (97.5%), moderate 1 in 81 cases (2.2%), moderate 2 in 3 cases (0.1%), and asymptomatic in 10 cases (0.3%).

In the safety analysis population, 379 events of non-serious adverse drug reactions (ADRs) were reported, and 5 events (headache, nausea, vomiting, cold sweat, and generalized oedema) of serious ADRs were reported. The major ADRs in the safety analysis population were diarrhoea in 91 cases (2.4%), nausea in 43 cases (1.1%), headache in 42 cases (1.1%), vomiting in 24 cases (0.6%), and rash in 20 cases (0.5%). The frequency of ADRs was 7.09% in the standard-risk (SR) group and 7.56% in the HR group. The median time to resolution of fever was 48.0 hours in the SR group (n=1929) and 36.0 hours in the HR group (n=590). The median time to resolution of all symptoms was 204.0 hours in the SR group (n=2732) and 156.0 hours in the HR group (n=903). Thirteen cases (0.4%) were hospitalized, and the reason was exacerbation of COVID-19 in 10 cases, and others in 5 cases.

Conclusion

Results of the analysis suggest that ensitrelvir is well tolerated and effective in patients with risk factors same with patients without risk factors.

Disclosures

Satoru Takashima, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Noriko Hayashi, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Eri Tsukimura, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Eriko Ogura, MD, Shionogi & Co., Ltd: Employee