bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2034. Inappropriate Outpatient Antibiotic Prescribing for COVID-19 in New York City, 2020—2022
Authors: Foote Mary K , Kochar Nisha , Thu Kyaw Nang Thu
Published: January 2025

Background

Antibiotic misuse is a key driver of antimicrobial resistance. Early in the COVID-19 pandemic, several unproven therapies were used, including antibiotics. In November 2020 and December 2021, monoclonal antibodies and oral antivirals were authorized for the outpatient treatment for COVID-19 respectively, which may have influenced inappropriate antibiotic prescribing (IAP). Here we describe prescribing trends and proportion of inappropriate antibiotic prescriptions for COVID-19 by patient and provider characteristics during 2020—2022 in New York City (NYC).

Methods

We performed a retrospective descriptive analysis of medical visits for COVID-19 during 2020—2022 identified by ICD-10 codes and associated antibiotic prescription fills using IQVIA medical data, which captures office-based physician and specialists visit claims, and prescription data, which captures 94% of retail pharmacy prescription claims. Medical visits with a concomitant diagnosis for conditions which may or do require antibiotics were excluded. Inappropriate antibiotic prescription (IAP) was defined as an antibiotic prescription claim linked to a COVID-19 medical visit within ≤7 days.

Results

Of 1,284,623 medical visits for COVID-19, 81,885 (6.4%) resulted in an antibiotic prescription fill, a majority were macrolides (62%). Most patients were seen in a clinic (32.4%) or urgent care (28.7%) and by a physician (85.2%), most frequently Internal Medicine (34.7%). Rates of IAPs were 5.5% in 2020, 6.7% in 2021 and 6.5% in 2022. Patients aged 50-64 years (8.7%), who were female (6.9%) or had a telehealth encounter (9.9%) received more IAPs than other groups. Antibiotics were more likely to be inappropriately prescribed by providers who were male (8.6%), aged ≥50 years (7.6%) or internal medicine physicians (9.0%).

Conclusion

Availability of COVID-19 treatments did not appear to decrease antibiotic prescribing. IAP was lower overall compared to national estimates but varied significantly by patient and provider characteristics. Limitations include lack of data on unfilled prescriptions, race, ethnicity, disease severity or underlying conditions. These findings can help target interventions to improve quality of treatment for COVID-19.

Disclosures

All Authors: No reported disclosures
P-2038. A Pharmacist-Run Treatment Decision Program for High-Risk Outpatients with Mild-Moderate COVID-19 at an Urban Veteran's Affairs Medical Center
Authors: Kuhn Ryan , Weslosky Lauren , Natesan Suganthini Krishnan , Dhar Sorabh
Published: January 2025

Background

Antiviral treatment is recommended for high-risk outpatients with mild-moderate COVID-19 to prevent progression to severe disease. Antiviral treatment decisions remain challenging due to the need for early initiation of treatment and the potential for drug-drug interactions with first-line therapy.

Methods

This single center, retrospective review evaluated the impact of a Pharmacist-run treatment decision program for high-risk outpatients with mild-moderate COVID-19 from 1/1/2022 through 12/28/2023. All outpatient treatment candidates were reviewed by a Clinical Pharmacist prior to initiation of oral antiviral treatment. A 5-day course of oral ritonavir-boosted nirmatrelvir (RNM) was considered first-line. A 5-day course of oral molnupiravir (MNP) was used as an alternative in situations where oral RNM was not clinically appropriate. The Clinical Pharmacist determined the optimal antiviral treatment, the appropriate medication dose, reviewed for drug-drug interactions, helped implement any necessary medication adjustments and/or monitoring plans, and assisted with patient education. Patient characteristics and the number of pharmacist interventions related to RNM drug-drug interactions were summarized.

Results

From 1/1/2022 to 12/28/2023, 455 high-risk outpatients were treated with oral antivirals for mild-moderate COVID-19 through the Pharmacist-run treatment decision program. Four-hundred and two patients (88.35%) were treated with RNM and 53 patients (11.65%) were treated with MNP. Patient ages ranged from 23 to 97 years (mean 66.4, SD 12.1). The mean duration of COVID-19 symptoms for patients who received oral antiviral treatment was 3 days (SD 1.12). The Clinical Pharmacist intervened on a total of 624 drug-drug interactions related RNM. The most common reason for use of MNP was the presence of major drug-drug interactions related to RNM (47/53; 88.7%), followed by severe renal impairment (6/53; 11.3%).

Conclusion

A Pharmacist-run treatment decision program for high-risk outpatients with mild-moderate COVID-19 was effective at initiating appropriate oral antiviral treatment in a timely fashion and ensuring patient safety by managing drug-drug interactions related to RNM.

Disclosures

All Authors: No reported disclosures
P-2045. Humoral Response induced by Three-Dose Vaccination Schemes Against SARS-CoV-2 in Pediatric Hematopoietic Stem Cell Transplant Recipients: Experience from a Middle-Income Country
Authors: Soffia Andrés , Le Corre M Nicole , Torres Juan Pablo , Cecilia Vizcaya M , Martinez-Valdebenito Constanza , González Natalia , Catalán Paula , Donoso Paulina , Barrera Aldo
Published: January 2025

Background

Hematopoietic Stem Cell Transplant (HSCT) recipients are at high risk for severe COVID-19, requiring effective vaccination strategies. SARS-CoV-2 inactivated vaccines elicit lower levels of neutralizing antibodies (NAbs) compared to mRNA vaccines and have been little studied in immunocompromised children. However, low- and middle-income countries predominantly use inactivated vaccines. Aim: to explore the immunogenicity of different COVID-19 vaccination strategies in pediatric HSCT recipients from Chile, where both vaccine types are used.

Methods

Multicenter cross-sectional study of pediatric HSCT recipients, previously immunized with 3-dose regimens based on CoronaVac/Sinovac (CV) and BNT162b2/Pfizer-BioNTech (BNT) vaccines >=3 months post-transplant. NAbs against the original Wuhan strain and the Omicron XBB1.5 variant were evaluated 8-12 weeks after the 3rd dose using a pseudovirus-based assay. A positive Nab titer was defined as a neutralizing activity of at least 50% (ID50) at a 1:160 dilution. Safety/reactogenicity outcomes were recorded.

Results

27 pediatric HSCT recipients were included (median age 11.9 y), of whom 21 were vaccinated with 2 doses of CV followed by a BNT booster, 1 with 2 doses of BNT followed by a CV booster and 5 with 3 BNT doses. At 11.1 weeks (IQR 9.2-13.6) after the 3rd dose, 84% reached NAb positivity for the Wuhan strain, while only 40% reached it for the XBB1.5 variant (P< 0.005). Neutralizing capacity was higher against Wuhan compared to XBB1.5, with a median ID50 of 2127 vs 75.9 (P< 0.0001). NAb-positive patients for the Wuhan strain had higher IgG levels (median 693 mg/dL vs 371.5 mg/dL in non-responders, P< 0.05). No significant differences were found in neutralizing capacity based on the scheme administered. In a multivariate linear regression, the CD19 count predicted neutralization capacity. No serious adverse events were reported.

Conclusion

No differences were observed in neutralizing capacity based on the vaccines administered, supporting the use of heterologous schemes including both inactivated and mRNA vaccines in HSCT pediatric recipients. Neutralizing capacity was higher against Wuhan than XBB1.5, emphasizing the importance of booster doses of bivalent vaccines that target this variant.

Disclosures

All Authors: No reported disclosures
P-2048. COVID-19 XBB.1.5 Vaccine Uptake Based on State Vaccine Registries Compared to National Survey Data
Authors: Cook Angela , Andersen Kathleen M , Brouillette Matthew A , McGrath Leah , McLaughlin John M
Published: January 2025

Background

Prior to May 11, 2023, all COVID-19 vaccinations were required to be reported by states to the Centers for Disease Control and Prevention. In the post-pandemic era, national vaccination uptake is now estimated using the National Immunization Survey (NIS). While survey methodology attempts to achieve random sampling of the population and accurate assessment of vaccine use through self-report, it is unknown how these estimates compare to state vaccine registries. We aimed to compare estimated COVID-19 vaccine uptake during the 2023-2024 season from state vaccine registries with estimates from the NIS.Figure 1.Uptake of XBB.1.5 COVID-19 vaccine in state vaccine registries versus national survey estimates, September 2023 - February 2024

Methods

We utilized two COVID-19 state vaccination registries where COVID-19 vaccine reporting was required: CAIR2 in California and LINKS in Louisiana. We identified COVID-19 XBB.1.5-adapted vaccines administered between September 11, 2023, and February 10, 2024, using CVX vaccine codes 308 - 313. California and Louisiana 2023 population estimates were obtained from the U.S. Census Bureau and used as the denominator to calculate population-level uptake. For the same time period, state-specific COVID-19 vaccine uptake estimates were also obtained from state-specific NIS data for California and Louisiana as a comparison.

Results

At the end of the study period, 14.4% of adults and 5.6% of children in California were documented as vaccinated in the CAIR2 registry compared to NIS estimates that 23.8% (1.6x) of adults and 17.3% (3.1x) of children in California had been XBB.1.5 vaccinated (Figure). For Louisiana, 5.4% of adults and 0.6% of children were found in LINKS registry data compared to NIS estimates that 12.3% (2.3x) of adults and 3.9% (6.5x) of children were XBB.1.5 vaccinated.

Conclusion

XBB vaccination coverage was low overall but was substantially lower when measured using state vaccine registry data compared with national survey data, especially for children. Efforts to improve COVID-19 vaccination are warranted, as are future studies to determine why COVID-19 uptake appears higher in national survey data compared to what is captured in state registries.

Disclosures

Angela Cook, MS, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Kathleen M. Andersen, PhD MSc, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Matthew A. Brouillette, MPH, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Leah McGrath, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) John M. McLaughlin, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-2075. Immunogenicity of co-administration of influenza vaccine and COVID-19 vaccine in healthy volunteers
Authors: Tongsengkee Nonthanat , Pinpathomrat Nawamin , Siripaitoon Pisud , Kositpantawong Narongdet , Kanchanasuwan Siripen , Chittrakarn Sorawit , Chusri Sarunyou
Published: January 2025

Background

The emergence of coronavirus disease 2019 (COVID-19) and seasonal influenza results in a substantial disease burden worldwide. The immunogenicity of co-administering the COVID-19 and influenza vaccines was not well established, as co-administration may reduce the antibody response. The aim of the study is to evaluate the humoral immune response (HIR) and cell-mediated immune response (CMIR) of co-administration among healthy volunteers.

Methods

A pilot randomized controlled trial was conducted in Southern Thailand from March to April 2024. Healthy adults who had received at least one dose of any COVID-19 vaccine more than 6 months prior were enrolled and randomly assigned (1:1:1) to receive the influenza vaccine (VaxigripTetra™) alone, the COVID-19 vaccine (bivalent mRNA BNT162b2) alone, or co-administration of both vaccines. T-cell response against SARS-CoV-2 by Interferon gamma enzyme-linked immunosorbent spot (IFN-γ ELISpot) assay and anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) level were measured before and 4 weeks after vaccination. The primary outcomes were the geometric mean ratio (GMR) of ELISpot and anti-RBD IgG level, with a lower bound 95% confidence interval (CI) > 0.67 for the non-inferiority margin (within 1.5-fold). The sample size was 12 per arm, according to the pilot study.

Results

Thirty-six participants were recruited. The enrollment and study flow are shown in Figure 1. Demographic data of participants are demonstrated in Table 1. Geometric means (GMs) for IFN-γ ELISpot and anti-RBD IgG are shown in Figure 2. GMRs between the co-administration and COVID-19 group were 1.03 (95% CI 0.43-2.44) for IFN-γ ELISpot and 0.82 (95% CI 0.52-1.29) for anti-RBD IgG, both failed to meet the non-inferiority margin due to the lower bound 95% CI < 0.67 (Figure 3). Mild solicited systemic adverse reactions in the influenza, COVID-19, and Co-administration groups were 8.3%, 75%, and 83%, respectively.

Conclusion

Co-administration of COVID-19 and influenza vaccines tended to show comparable both HIR and CMIR, as well as adverse reactions, with COVID-19 vaccination alone. This finding may support co-administration policy. According to pilot study, larger sample size study and effectiveness of vaccine co-administration need to be investigated.

Disclosures

All Authors: No reported disclosures
P-2109. Culture-Free Identification of Microbes in Seconds Directly from Clinical Samples using the MasSpec Pen Technology
Authors: Downey Rachel , Kumar Manoj , Kirkpatrick Lindsey M , Hauger Sarmistha Bhaduri , Johnson Coreen , Dunn James , Jackobs Faith , Keating Michael , Eberlin Livia
Published: January 2025

Background

Broad spectrum antibiotics are often used empirically in cases of suspected invasive infection requiring surgical intervention while awaiting results of conventional testing (cultures and molecular tests). Rapid and accurate diagnosis of the etiologic pathogens is critical to allow for selection of targeted antibiotics and improve outcomes for patients.

We present current results of a large, multi-center clinical study using the MasSpec Pen (MSPen) technology to characterize the metabolic profiles of clinically relevant microbes in culture isolates and apply the technology to culture-independent identification of infectious agents directly in clinical samples.Figure 1.Schematics showing the key operating steps and results when using the MasSpec Pen to perform analysis and identification of bacteria.

Methods

The MSPen allows direct sample analysis using a solvent droplet followed by immediate mass spectrometry analysis, with total acquisition time of ∼15 seconds (fig 1). In this study 785 samples (635 isolates and 150 clinical specimens) were analyzed using this technology to create distinct metabolic profiles to differentiate bacterial pathogens. 80% of data were used as a training set to develop such profiles; 20 percent of data were used as a test set to identify bacterial infection.Fig 2.Species identification in pure isolates

Results

We identified over 400 bacterial metabolites and lipids in 10 different microbial species and compiled a unique metabolic profile for each that was used to directly identify specific microbes in cultures and clinical specimens.

Among culture isolates, our statistical classifiers were able to achieve 99% accuracy for Gram-typing, and 99% accuracy among 10 bacteria in the test set (fig 2).

Using species-specific metabolites and lipids, we were able to identify Pseudomonas aeruginosa directly from 3 infected specimens and Staphylococcus epidermidis directly from infected bone.

Conclusion

Our results show the incredible promise that direct MSPen analysis has for rapid, culture-independent identification of bacteria from patient tissues. We are working to build classifiers to differentiate bacteria by specific m/z values to improve identification in tissue samples.

Disclosures

Manoj Kumar, PhD, LSE is an inventor in patents related to the MSPen technology owned by University of Texas Austin and Baylor College of Medicine. LSE is a co-founder,: LSE is an inventor in patents related to the MSPen technology owned by University of Texas Austin and Baylor College of Medicine. LSE is a co-founder, Lindsey M. Kirkpatrick, DO, PhD, Thermo Fisher Scientific: Honoraria Michael Keating, PhD, MS Pen Technologies: Advisor/Consultant Livia Eberlin, PhD, Merck: Honoraria
P-2116. Analysis of No-Growth Wells in Escherichia coli (EC) During Fosfomycin Broth Microdilution (BMD) and Agar Dilution (AD) Testing
Authors: Salay Jenna , Malik Khadijah , Collins Lindsey , Chang Tiffany , Bixby Morgan L , Bixby Morgan L , Hirsch Elizabeth B
Published: January 2025

Background

Although AD is the reference method for CLSI and EUCAST, it is not clinically efficient. Neither CLSI nor EUCAST approve the use of BMD due to less precision, trailing endpoints, and presence of no-growth wells before the minimal inhibitory concentration (MIC). However, available data describing these phenomena are very limited. We sought to evaluate rates of scientific error—no-growth wells and growth at concentrations above the MIC in BMD and AD—among a collection of EC isolates, to determine if BMD is truly less precise than AD.

Methods

A convenience collection of EC clinical urine isolates (n = 106) collected in 2022 was included. BMD and AD were performed in technical triplicate and in biological duplicate on separate days to determine a final MIC. A measured MIC was defined as the MIC obtained from a single biological replicate whereas the final MIC was the shared MIC (± 1 dilution) between two biological replicates of the same isolate. For AD, MIC were determined from the first concentration with no growth or only a single colony formed; for BMD: lowest concentration with no visible growth in all three technical replicates. For BMD, a no-growth well was defined as lack of growth at any concentration below the MIC. Growth above the measured MIC was defined as a single well with any visible growth at a concentration greater than the MIC. For AD, error was recorded as any single colonies at the MIC or any countable colony growth at concentrations above the MIC.

Results

The collection had a range of final MIC from 0.5 to > 64 µg/mL for AD and BMD (Table 1). For BMD final MIC including data for > 2 isolates, no-growth wells occurred up to 38.1% of the time (Figure 1A). Additional growth beyond the MIC occurred up to 16.7% of the time (Figure 1B). Single colonies at or beyond the MIC occurred up to 50% of the time (Figure 1C).

Conclusion

Rates of no-growth wells and growth at concentrations higher than the measured MIC for fosfomycin BMD and AD testing was high among a collection of EC isolates, which resulted in frequent scientific error. BMD had increased rates of scientific error while reading results. Additional analysis using a larger isolate set is needed to further validate these results; however, the frequency of error demonstrated for both testing methods should prompt re-evaluation of fosfomycin BMD and AD testing.

Disclosures

Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, GSK: Advisor/Consultant|GSK: Honoraria
P-2121. A prospective observational study of usefulness of interferon-gamma release assay for latent tuberculosis infection in pediatric hematopoietic stem cell transplant recipients
Authors: So Hyejin , Lee Jina
Published: January 2025

Background

Pediatric hematopoietic stem cell transplantation (HSCT) recipients are one of the high-risk groups concerning tuberculosis and screening for latent tuberculosis infection (LTBI) prior to HSCT is important and accurate diagnostic tests for predicting LTBI in these high-risk children are on demand. However, there are concerns for Interferon-gamma release assay(IGRA) being less sensitive in the children group for screening LTBI. This study was aimed to evaluate the predictive value of Quantiferon-TB Gold test (QFT-G) using the enzyme-linked immunosorbent spot assay (T-SPOT.TB) in immunocompromised Korean children.

Methods

In this prospective observational study, children under age 20 who were scheduled for allogeneic HSCT at Asan Medical Center Children`s Hospital were enrolled during March 2017 and May 2018. QFT-G test and T-SPOT.TB were done prior to HSCT. Concordance rates were calculated among each group. Electronic Medical Records was reviewed for clinical and demographic data of the enrolled patients.

Results

Among the 62 patients who were planned to receive allogenic HSCT during March 2017 and May 2018, 11 patients were excluded and a total of 51 patients were enrolled. Median age was 10 years and the underlying disease leading to HSCT was mostly aplastic anemia (31.4%). Others were acute myeloid leukemia (23.5%), acute lymphoblastic leukemia (15.7%), myelodysplastic syndrome (7.8%), and other benign disease (17.6%). About 52% of the patients were applied immunosuppressive drugs in the recent 3-month period prior to testing. 4 patients were considered LTBI based on screening test results. At 2 year follow up period, 1 patient was confirmed pulmonary TB. Overall concordance rate was 82.4% (42/51). The age-based concordance rate was 93.8% (14/15) for children younger than 5-years old and 77.8% (28/36) for 5 or above. Concordance rate between negative test results and not TB diagnosis was further checked; QFT-GIT 97.8% (44/45), T-SPOT. TB 97.9% (46/47), and TST 100% (10/10).

Conclusion

This study shows that the GFT-GIT well matched with the T-SPOT.TB for screening LTBI and children under age 5 showed to have higher concordance rates compared to the older age group. This could provide evidence to testing younger children with IGRA assays.

Disclosures

All Authors: No reported disclosures
P-2122. Spectrum of Infection and Outcomes in Individuals with Candida auris Infection in Qatar
Authors: Al Ajmi Jameela A , Malik Aimon , Nafady-Hego Hanaa , Hanana Fathima , Abraham Joji , Garcell Humberto G , Hudaib Ghada , Al-Wali Walid , Eltayeb Faiha , Shams Sherin , Thomas Anil G , Saleem Samah , Abou-Samra Abdul-Badi , Butt Adeel A
Published: January 2025

Background

We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar.

Methods

We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality.

Results

Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had > 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P=0.002), and longer hospital length of stay (63 vs. 43 days; P=0.003), and higher 30-day mortality (38% vs. 14%; P< 0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17).

Conclusion

Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation with any positive C. auris cultures should be especially monitored for development of invasive fungal disease.

Disclosures

Adeel A. Butt, MD, MS, Gilead Sciences: Grant/Research Support
P-2197. Pharmacist-Led Hepatitis C Virus Model of Care Effectively CURES Simplified Cases
Authors: Sheehan Lindsey , Wright Maribeth P , Stacey Morgan , Fritz Anthony , Rhudy Christian , Moore Daniel
Published: January 2025

Background

Despite the existence of curative direct acting antiviral therapy, hepatitis C Virus (HCV) prevalence and mortality has increased in many regions of the United States. Existing models of care have failed to yield treatment rates needed for HCV elimination by 2030. In June 2023, we implemented UK-CURES (University of Kentucky - Cascade Utilizing Routinized screening through treatment to Eliminate Syndemics), a novel model of HCV care (Figure 1). This pharmacist-led model utilizes collaborative care agreements to carry out AASLD/IDSA best practices at the point-of-care in an effort to eliminate variation and waste along the HCV cascade.Figure 1.UK-CURES Simplified Treatment Algorithm

Methods

This study is a retrospective descriptive analysis including patients evaluated by the UK-CURES team between 6/1/2023 and 5/1/2024. Patients were excluded from this analysis if they were not eligible for the UK-CURES HCV simplified treatment algorithm. Patient demographics, clinical and operational data were collected from electronic medical record modifications. Patients were considered lost to follow-up if they had not engaged with treatment 120 days and had not completed sustained virologic response (SVR12) laboratory results. Results are summarized with descriptive statistics.

Results

1,428 patients were evaluated by the UK-CURES team, of whom 1,105 were excluded from the treatment algorithm. The primary reason for exclusion was a negative confirmatory HCVRNA laboratory test (n = 579, 52.5%). Of 323 patients treated, demographics and baseline status are displayed in Table 1. Median time from first UK-CURES encounter to treatment order was 2 days, while the median time to first treatment dispense was 12 days (Table 2). Less than half of treated patients were lost to follow-up prior to obtaining SVR12 results (n = 147; 45.5%), and remaining patients are currently engaged in therapy (n = 141; 43.7%) or have completed SVR12 results (n = 35; 10.8%) (Figure 2). 32 patients (91%) were undetectable at SVR12.Figure 2.UK-CURES current patient status and attrition diagram

Conclusion

Our novel pharmacist-led model of care, UK- CURES, improved key performance indicators along the HCV care cascade for simplified cases while maintaining best practices surrounding HCV guidelines. The success of this model has significant implications for future HCV elimination efforts.

Disclosures

Maribeth P. Wright, RPh, CSP, Gilead FOCUS Program: Gilead FOCUS grant support Christian Rhudy, PharmD, MBA, Amgen, Inc.: Grant/Research Support Daniel Moore, MD, MBA, FACEP, Gilead FOCUS: Grant/Research Support
P-2221. Clinical utility and sensitivity of plasma metagenomic microbial cell-free DNA sequencing in children with complicated pneumonia
Authors: Ho Erin C , Asturias Edwin J , Butler Molly , Simmons Dennis , Dominguez Samuel R
Published: January 2025

Background

Etiological diagnostics for children with complicated bacterial pneumonia remain limited and insensitive, and pleural fluid (PF) testing is invasive. Plasma metagenomic microbial cell-free DNA (mcfDNA) sequencing, available by Karius, Inc., is a potentially comprehensive, non-invasive, and efficient diagnostic tool for pediatric pneumonia. However, rigorous studies comparing the real-world performance of mcfDNA to other testing modalities are lacking.

Methods

We compared the performance of the Karius Test (KT) to blood culture, PF culture, and in-house PF PCR assays targeting the most common pathogens in complicated community acquired pneumonia (cCAP), including Streptococcus pneumoniae (Spn), group A Streptococcus (GAS), and Staphylococcus aureus, in immunocompetent children hospitalized with cCAP requiring pleural effusion or empyema drainage at Children’s Hospital Colorado from 2022-2024. We calculated percent agreement across tests and sensitivities using both a composite reference standard and clinical truth. Bacterial pathogens were adjudicated by three infectious disease physicians as probable, possible, or unlikely cCAP pathogens. DNA virus detections on KT were not considered causative of cCAP.

Results

In our cohort of 32 children with cCAP (Table 1), 84.4% (27/32) had at least one probable pathogen identified by KT alone vs. 75% (24/32) by all other testing combined (Table 2). GAS (37.5%) and Spn (31.3%) were the most commonly detected pathogens, and 15.6% had > 1 probable pathogen detected. Compared to a composite reference standard, KT had the highest sensitivity (91.1%), followed by targeted PF PCR assays (67.6%), PF culture (26.5%), and blood culture (12.5%), with similar trends by clinical truth. Positive agreement between KT and PCR + culture was 88.9%. Most KT samples were collected within 5 days of starting effective antibiotic therapy, but KT remained positive even up to 10 days on therapy (Figure 1).

Conclusion

Compared to culture and PF PCR-based testing, KT had higher sensitivity and excellent positive agreement for etiological diagnosis of pediatric cCAP. Early use of KT may be a promising diagnostic strategy, especially in the setting of antibiotic pre-treatment. Further studies are needed to determine KT specificity and clinical impact.

Disclosures

Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Merck: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Molly Butler, PhD, Pfizer: Conference Attendance Samuel R. Dominguez, MD, PhD, BIofire Diagnostics: Advisor/Consultant|BIofire Diagnostics: Grant/Research Support|DelveBio: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Pfizer: Grant/Research Support
P-2260. Incidence and clinical characteristics of acute viral infections in the first year after hematopoietic stem cells transplantation. Argentine single center cohort
Authors: Huaier Arriazu Emilio F , Giunta Diego H , Basquiera Ana L , Mañez Noelia , De Boeck Julieta M , Diaz Lobo Emilse D , Rolan Martin A , Visús Mariángeles , del Lujan Sanchez Marisa
Published: January 2025

Background

The incidence and mortality of respiratory virus infections (RVI) in patients receiving a Hematopoietic Stem Cell Transplant (HCT) is variable, and changes depending on place, year and season. They can present as upper respiratory tract infection (URTI) or lower respiratory tract infection (LRTI), with the latter having a worse prognosis. There is no data from Argentina in the adult population. Objectives: estimate the incidence of RVI in the year after HCT and associate risk factors for clinical evolution, progression from URTI infection to LRTI, requirement for Intensive Care Unit (ICU) and mortality.

Flow chart of HCT recipients and respiratory events, with a diagnosis of respiratory viral infection within one year after transplant.

Methods

retrospective cohort study of the population of patients receiving HCT from 11/2011 to 12/2019. The patients were followed for one year, and for one month after each RVI.

Kaplan-Meier curve of the incidence of IRVA according to type of HCT.

Results

Out of 476 HCT with 30.7% allogeneic, 99 confirmed RVI were detected. The Cumulative Incidence at 100 days post-transplant was 1.99 (95% CI 1,0 - 3,95) per 100 patients, while at one year, it was 28.81 per 100 patients (95% CI 24.32 - 33). ,93). The HR of RVI in allogeneic HCT was 2.45 (95% CI 1.72-3.51; p < 0.001) compared to autologous. Also was lower in lymphoma 0.5 (95% CI 0.29 - 0.85) and Multiple Myeloma 0.36 (95% CI 0.22 - 0.58) compared to leukemia (p < 0.001) as the underlying disease. Although there were differences in the clinical status and characteristics evaluated at the diagnosis of RVI, no relevant associations were found at day 7 of follow-up. 53.5% of RVI events presented as URTI, and 16.9% progressed to LRTI. An association was found between male sex, OR of 0.20 (95% CI 0.06-0.73; p< 0.001) and the occurrence of the event beyond 28 days after transplant, 0.27 (95% CI 0.08 -0.95; p=0.045), while RVI in hospitalized patients had an OR of 5.71 (95% CI 1.61-20.24; p=0.006) for progression. Only 16% required ICU, there was an association between age over 65 years, event before 28 days post HCT, myeloablative conditioning, use of corticosteroids at the time of the event, RVI during hospitalization and hypoxemia and requiring ICU. Mortality was 2.1% (95% CI 0.67-6.32) within 30 days of RVI.

Conclusion

The Cumulative Incidence was similar to other reports, however the mortality was lower.

Disclosures

All Authors: No reported disclosures
P-2263. Are you PRePared After Transplant?
Authors: Grabell Jylian , Mishkin Aaron D , Burnell Jacqueline , Altneu Eric
Published: January 2025

Background

Solid organ transplantation (SOT) is a life-saving medical procedure that can improve the quality of life of individuals with end-stage organ failure. Given the scarcity of organs, it is important to safeguard those implanted and prevent infections. Transplant Infectious Disease physicians help mitigate infectious risk both before and after surgery. One important preventable infection is Human Immunodeficiency Virus (HIV). Pre-exposure prophylaxis (PrEP) is effective in reducing the risk of HIV infection. Yet no study has examined PrEP use in SOT patients. The CDC reports that 30% of patients that may benefit from PrEP are prescribed them in the US. No similar statistic exists for SOT patients.

Figure 1

Demographics for SOT patients with possible exposure to HIV. Purple represents those without PrEP. Green represents those with PrEP.

Methods

To obtain quantitative support for further study, a large, multi-center database (Trinetx) was queried. Trinetx contains deidentified data from hundreds of international healthcare organizations (HCOs) dating back about seven years. The retrospective query included 68 HCOs with patients that met the following search inclusion criteria (based on ICD codes): SOT patient without the diagnosis of HIV, prescribed PrEP, and possible exposure risk for HIV.

Results

147,145 SOT patients were identified that did not carry the diagnosis of HIV. Only 160 patients (0.11%) were prescribed PrEP, identified as the following three regimens: tenofovir alafenamide + emtricitabine, tenofovir disoproxil + emtricitabine, or cabotegravir.

To risk-stratify HIV exposure, the original cohort of 147,475 SOT patients without HIV were analyzed with ICD codes for HIV exposure. This search identified 2,565 patients coded for HIV exposure. Given that only 160 patients were prescribed PrEP in the cohort, 2,405 patients may have benefited from PrEP but were not prescribed these medications. Patients on PrEP after SOT were predominantly male (78%) and White/Caucasian (58%). Identifying as Asian was a significant factor in using PrEP after SOT (p< 0.0001). Female gender was a significant demographic not utilizing PrEP despite possible exposure to HIV (p< 0.0001). (Figure 1).

Conclusion

This large database study shows that PrEP is underutilized in SOT patients. Further study—including surveys of sexual practices, provider knowledge, and attitudes towards PrEP, as well as single-center analysis—is needed.

Disclosures

All Authors: No reported disclosures
P-2313. Multinational, Retrospective Study Assessing Outcomes and Healthcare Resource Utilization in Hematopoietic Stem Cell Transplant Recipients with Cytomegalovirus Infection and Refractory, Resistance, or Intolerance to Anti-Cytomegalovirus Treatments: Analysis of Impact of Viremia Clearance on Outcomes
Authors: Davis Kimberly , Mendonça Ines , Bo Tien
Published: January 2025

Background

Cytomegalovirus (CMV) infection is a risk factor for morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. This real-world analysis describes the impact of viremia clearance on outcomes in HSCT recipients with refractory, resistant or intolerant (RRI) CMV infection to anti-CMV agents.

Methods

This multicenter, retrospective chart review study included adult HSCT recipients with RRI CMV infection. Data between 2014 and 2021 were collected from 14 centers in Europe and the USA. The analysis descriptively compared demographics, patient characteristics, clinical outcomes, and hospitalizations in patients who did versus did not achieve viremia clearance during the first RRI CMV episode.

Results

Among 247 patients with a first RRI CMV episode, 145 (59%) achieved viremia clearance and 102 (41%) did not. In patients with vs without viremia clearance, respectively, median age was 53 vs 60 years, and 46% vs 58% were male. Of the 145 and 102 first RRI CMV episodes with vs without viremia clearance, respectively, 52% vs 75% were identified as refractory, 61% vs 31% as intolerant, and 3% vs 9% as resistant (categories not mutually exclusive); 9% vs 15% of patients developed tissue invasive disease. CMV recurrence occurred in 35% vs 37% and graft failure in 3% vs 6% of patients with vs without viremia clearance, respectively (Table). Myelosuppression and nephrotoxicity events during CMV episodes were reported in 54% vs 44% and 26% vs 27% of patients with vs without viremia clearance, respectively (Table). CMV-related hospitalizations with/without emergency department visits occurred in 35% of patients with viremia clearance vs 43% of patients without viremia clearance (Table). Notably, the overall mortality within 1 year of RRI identification in patients without viremia clearance was higher than in those with viremia clearance (68% vs 30%, respectively).

Conclusion

These results highlight the high disease burden in HSCT recipients with RRI CMV infection. In this difficult-to-treat population, the mortality rate was higher in patients without viremia clearance than in patients with viremia clearance.

Disclosures

Kimberly Davis, RPh, MS, Takeda: Employee|Takeda: Stocks/Bonds (Public Company) Ines Mendonça, MSBiostats, CTI Clinical Trial & Consulting Services: Employee (paid to provide consulting services including medical writing and statistical analysis) Tien Bo, PharmD, Takeda: Employee|Takeda: Stocks/Bonds (Public Company)
P-2322. Screening Rates and Clinical Outcomes for Hepatitis Delta in Individuals with HBV Coinfection
Authors: Butt Adeel A , Yan Peng , Shaikh Obaid , Bedimo Roger
Published: January 2025

Background

Hepatitis Delta (HDV) screening is recommended for those with hepatitis B virus (HBV) infection. However, screening rates are not well documented and are far from ideal. Factors associated with screening for HDV, and clinical outcomes among HBV/HDV coinfected individuals are poorly understood. Our aim was to define the screening rates for HDV among HBV infected individuals, and the incidence of various complications among HBV/HDV coinfected individuals in the US VA healthcare system.

Incidence rates for cirrhosis, hepatic decompensation, and hepatocellular carcinoma among those with HBV and HBV/HDV coinfection.

Methods

Within the Veterans Health Administration (VA) national databases, we identified all individuals with HBV (defined as a positive test for HBV surface or “e” antigen, or HBV DNA) between 2002-2023. Screening for HDV was ascertained by serology or HDV PCR testing. Incidence rates for development of cirrhosis, hepatic decompensation (HD), hepatocellular carcinoma (HCC), and death were calculated for those with HBV alone and those with HBV/HDV coinfection.

Kaplan-Meier curves demonstrating progression to cirrhosis, Hepatitis D, and Hepatocellular Carcinoma

Results

Of the 44,951 individuals with HBV, 5,964 (13.3%) were screened for HDV and 180 (3% of those tested) were positive for HDV. Among 38,472 individuals without baseline cirrhosis, the incidence rates/100 person years (95% CI) for cirrhosis, HD, and HCC were 1.03 (0.52,1.53), 1.79 (1.18,2.4), and 1.91 (1.29,2.52) respectively among those with HBV/HDV coinfection compared with 0.60 (0.58,0.63), 0.72 (0.69,0.74), and 0.49 (0.47,0.51) among those with HBV infection alone. Kaplan-Meier curves demonstrated a higher proportion and accelerated progression to cirrhosis, HD, and HCC among HBV/HDV coinfected compared with HBV monoinfected individuals.

Conclusion

There are significant gaps in screening for HDV among HBV infected individuals. Those with HBV/HDV coinfection are more likely to develop serious complications compared with those with HBV alone.

Disclosures

Adeel A. Butt, MD, MS, Gilead Sciences: Grant/Research Support
P-2327. West Nile Virus Disease in the Veterans Health Administration (VHA), 2010-2023
Authors: Lucero-Obusan Cynthia A , Oda Gina , Chung Joyce S , Holodniy Mark
Published: January 2025

Background

Increasing evidence exists that West Nile Virus (WNV) transmission, distribution, and incidence is impacted by climate change. WNV is the most common mosquito-borne disease in the U.S., but there is little data in Veterans. Herein, we describe the epidemiology of WNV in VHA during 2010-2023.

Methods

WNV-coded hospitalizations, visits, and laboratory results were obtained from VHA data sources (1/1/2010-12/31/2023). We included individuals aged 18 years and above with ICD-9/10-CM WNV-coded encounters and/or a positive WNV IgM or PCR result. Data extracted included demographics and geography, diagnosis codes, test results, encounter details, and deaths during WNV-coded hospitalizations. Data were compared to CDC ArboNET.

Results

A total of 1,140 unique patients were identified. Of these, 762 (67%) were via ICD code only, 282 (25%) via ICD code & test result, and 96 (8%) via test result only. Annual case counts fluctuated but generally followed national trends, with highest activity observed in 2012, 2013 & 2018 (Fig. 1). Median age was 66 years and 92.4% were male. The highest proportion of cases were in males age 70+ (36%), which was also most common in ArboNET, although the percentage was lower (13%). 509 (44.6%) were coded as WNV encephalitis/neurologic manifestation and/or tested positive in the CSF, compared to ArboNET where 50.7% were classified neuroinvasive (1999-2022). Prevalence rates per 100,000 VHA population were highest for White (21.2) and American Indian/alaskan Native (AI/AN, 19.6) race and lowest in Asian (4.5). Average Annual case rates were highest in: South Dakota (16), Nebraska (11), North Dakota (6.6), and Colorado (5.1) (Fig. 2). There were 5,149 WNV outpatient visits (923 individuals). For 351 recorded hospitalizations (285 individuals), median stay was 11 days with 66 (18.8%) admitted to intensive care and 29 deaths during a WNV-coded hospitalization (8.3%).

Conclusion

WNV causes substantial morbidity and the burden is likely underestimated as asymptomatic and mild cases may never seek care. VHA WNV activity tracks closely with national CDC ArboNET reporting. Additional targeted education may increase awareness and testing among at risk individuals, particularly in high incidence geographic areas.

Disclosures

All Authors: No reported disclosures
P-73. Pyogenic And Brucellar Spondylodiscitis: Comparative Analysis Of Clinical, Laboratory, And Evolutionary Features
Authors: Hammami Fatma , Rekik Khaoula , Smaoui Fatma , Chakroun Amal , Marrakchi Chakib , Koubaa Makram , Ben Jemaa Mounir
Published: January 2025

Background

Spondylodiscitis is an infection of the vertebral and the intervertebral disc. The clinical presentation varies according to the underlying etiology. We aimed to compare the clinical, laboratory and evolutionary features between pyogenic and brucellar spondylodiscitis.

Methods

We conducted a retrospective study including patients hospitalized in the infectious disease department for pyogenic or brucellar spondylodiscitis between 1998 and 2022.

Results

We encountered 44 cases of brucellar spondylodiscitis (BS) (50.6%) and 43 cases of pyogenic spondylodiscitis (PS) (49.4%). Patients with PS were significantly older (60±16 years vs 50±16 years; p=0.007). A rural origin was significantly more frequent among BS patients (88.6% vs 55.8%; p=0.001). While motor deficit was significantly more frequent among PS patients (33.3% vs 11.4%; p=0.014), nights sweats were significantly more frequent among BS patients (72.7% vs 25.6%; p< 0.001). As to gender, fever and back pain, no significant difference was noted. The lumbar spine was the most affected site among BS group (74.4%) and PS group (72.1%), with no significant difference (p=0.8). Laboratory investigations including white blood cells count (11153±4952/mm3 vs 6719±2910/mm3; p< 0.001), erythrocyte sedimentation rate (84±31mm/h vs 50±33mm/h; p< 0.001) and C-reactive protein levels (108±87mg/l vs 32±28mg/l; p< 0.001) were significantly higher among PS group. Surgical treatment was indicated in 9.3% of PS cases and in 2.3% of BS cases, with no significant difference (p=0.3). Two patients with PS were dead (4.6%). Sequelae were noted among PS cases (41.9%) and BS cases (38.6%), with no significant difference (p=0.7).

Conclusion

Although PS patients were older, presented more frequently with motor deficit and had higher inflammatory markers, the disease evolution was similar in comparison with BS patients.

Disclosures

All Authors: No reported disclosures
P-92. Risk factors, Clinical Manifestations and Management of Vertebral Osteomyelitis due to Coccidioides: a 10-year Retrospective Descriptive Study
Authors: Wolf Sona R , Donovan Fariba , Robishaw-Denton Jacob , Riaz Talha
Published: January 2025

Background

Vertebral osteomyelitis is a severe manifestation of disseminated coccidioidomycosis with limited published data on clinical presentations and outcomes. The purpose of this study was to describe the epidemiology, risk factors, clinical features, management, and outcomes of coccidioidal vertebral osteomyelitis (CVO) among a cohort of patients in an endemic region.

Methods

We conducted a retrospective chart review of patients treated for CVO between 2013 and 2022 at an academic health system in Arizona. Demographic and clinical data were extracted.

Results

Forty-two patients with CVO were identified. The mean age at diagnosis was 36.3 (range, 18.9-73.2 years). Thirty-four (81%) patients were males and 33 (79%) were African American. Nine (21%) had a prior or current history of incarceration. Fifteen (36%) patients had a history of coccidioidomycosis including pulmonary (n=9), skin/musculoskeletal (n=5), and CNS infection (n=1) prior to diagnosis of CVO. Known comorbidities included long-term corticosteroid use (n=2), HIV infection (n=2), and pregnancy at time of CVO diagnosis (n=3 of 8 females). Of the 37 patients with complement fixation titers available at time of presentation, 25 patients had a titer >=1:128. The most frequent imaging findings identified via CT or MRI were paraspinal/epidural abscesses (n=32) or bone lytic lesions/erosions (n=32). All patients received triazole therapy, 32 (76%) received amphotericin B (median 15.5 days) at some point during their treatment course, and 4 (10%) received an investigational drug. Sixteen (38%) patients underwent surgical debridement and spinal fixation hardware was placed in 13 (31%). Thirteen (31%) patients experienced disease progression warranting re-admission. Four (10%) died within 3.5 years of diagnosis and all deaths were secondary to complications associated with CVO.

Conclusion

There is a high morbidity and mortality due to CVO. Most patients with CVO are African American males and few have predisposing comorbidities. A remarkably high proportion (21%) have a history of incarceration suggesting it may be a risk factor for CVO. A better understanding of the factors that predispose individuals to CVO and better therapies are urgently needed to improve outcomes in this frequently devastating illness.

Disclosures

Fariba Donovan, MD, PhD, F2G: Advisor/Consultant|F2G Ltd: Advisor/Consultant|F2G Ltd: Grant/Research Support|F2G Ltd: Honoraria