bluuebunny/crossref_metadata_2025_split huggingface dataset:
845. Clinical Outcomes in Patients Treated with High vs. Standard Dose Liposomal Amphotericin B for Invasive Mucormycosis
Authors: Valiante Sarah , Elshaboury Ramy H , Wu Tiffany , Reyes Fabiola , Lahoud Chloe , Franceschi Andres E , Koo Sophia , Letourneau Alyssa R , Hammond Sarah P 
Published: November 2023

Abstract

Background
Mucormycosis is a life-threatening invasive fungal infection associated with high mortality. Amphotericin B is first-line therapy; however, the benefit of high doses remains uncertain. The purpose of this study is to describe outcomes in patients treated with high dose versus standard dose liposomal amphotericin B (L-AMB) for mucormycosis.

Methods
This was a retrospective cohort study of adults ≥ 18 years treated with L-AMB for proven or probable invasive mucormycosis at Massachusetts General Hospital and Brigham & Women’s Hospital from 2016-2022. L-AMB dosing was based on clinician preference. Patients were excluded if L-AMB began &gt; 7 days prior to admission. Patients were categorized per L-AMB dose: standard dose (all doses &lt; 6 mg/kg) and high dose (≥ 6 mg/kg for at least one dose). The primary outcome was 6- and 12-week mortality.

Results
67 patients were treated with L-AMB for proven or probable mucormycosis during the study period: 57 with standard dose and 10 with at least 1 high dose of L-AMB. Baseline characteristics are shown in Table-1. More patients in the standard dose group had underlying hematologic malignancy. About one third of patients had underlying diabetes and this was evenly distributed between groups. Table-2 shows infection- and treatment-related details. Proven invasive mucormycosis was diagnosed in 51/57 (89%) and 6/10 (60%) patients in the standard and high dose groups, respectively. The most common site of infection in both groups was skin/bone. Approximately 35/57 (61%) and 8/10 (80%) patients in the standard and high dose groups, respectively, had surgical debridement. Mortality at 6- and 12- weeks and renal toxicity outcomes are shown in Table-3. In the entire cohort at 6- and 12 weeks death occurred in 25/67 (37%) and 33/67 (49%) patients, respectively; no difference in mortality was seen between the standard and high dose groups. There appeared to be no difference in renal outcomes, though more patients in the standard dose group required renal replacement therapy within 6-weeks of diagnosis.

Conclusion
We observed no difference in 6- and 12-week mortality among patients treated with L-AMB at standard and high doses for invasive mucormycosis. Mortality at 6- and 12-weeks of mucormycosis diagnosis remains high.

Disclosures
Ramy H. Elshaboury, PharmD, DayZero Diagnostics: Advisor/Consultant|Gilead, Inc: Grant/Research Support|Thermofisher: Grant/Research Support Sophia Koo, MD, SM, Aerium Therapeutics: Advisor/Consultant|GSK: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant
862. Machine Learning to Differentiate Group A Streptococcal (GAS) from Non-GAS Pharyngitis Using a Custom Smartphone App
Authors: Hamdy Rana F , Nguyen Trong , Ansusinha Emily , Arjoune Youness , Dome Jeffrey S , Shekhar Raj 
Published: November 2023

Abstract

Background
Sore throat is one of the top three reasons for ambulatory pediatric visits in the United States. Approximately one-third of children with sore throat are diagnosed with GAS pharyngitis, for which antibiotics are indicated. Because symptoms and physical exam-based clinical prediction rules are insufficient to accurately diagnose GAS pharyngitis, laboratory testing is needed for conclusive diagnosis. Antibiotics are frequently overprescribed for pharyngitis, especially in the telemedicine setting where testing is not readily at hand. We developed a custom mobile app, StrepApp, to capture throat images and apply machine learning (ML) to distinguish GAS pharyngitis from other causes of sore throat.

Methods
We enrolled patients &gt;3 years old presenting with sore throat in the Children’s National Emergency Department. Using StrepApp, we collected throat images and presenting clinical symptoms. We defined GAS pharyngitis as a positive microbiologic GAS test and absence of upper respiratory infection (URI) symptoms; non-GAS pharyngitis was defined as those with negative microbiologic tests. We excluded patients who had received an antibiotic active against GAS in the previous 48 hours, those whose captured images were of poor quality or those with incomplete data, missing labs, or a positive GAS test in a patient presenting with URI symptoms. For ML classification, Scale Invariant Feature Transform (SIFT) was applied to throat images. Visual features were combined with clinical symptoms as input into a support vector machine (SVM) classifier to make a GAS versus non-GAS determination (Figure 1). We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the trained classifier.

Results
Of 262 patients enrolled, 148 images were analyzed. Curated images were split into 77 training images and 33 test images (Figure 2). The overall accuracy of the SVM classifier was 93.9%. The sensitivity, specificity, PPV, and NPV were 50.0%, 96.8%, 50.0%, and 96.8%, respectively.

Conclusion
StepApp shows promise to distinguish GAS from non-GAS pharyngitis with high specificity. The small sample size of the database allowed only conventional machine learning. As the database expands, deep learning with superior results may be possible.

Disclosures
All Authors: No reported disclosures
864. Can Population Risk Factors be Directly Applied to Guide Individual Patient’s Diagnosis and Treatment in Clinical Practice? – the Need to Re-Direct Epidemiology Research for Clinical Application in the Future
Authors: Huang Chaorui C , Xu Hong 
Published: November 2023

Abstract

Background
The implementation of population risk factor-guided diagnostic approach and treatment regimen has been widely considered in clinical practice to treat individual patient. However, the meaning of these risk factors, which are primarily developed from population-based epidemiology studies and thus presented probability and risk/odds ratio, are hard to interpret in clinical settings for individual patient. In this study, we provided an example of risk analysis for COVID-19 early intervention, in which the diagnostic accuracy of a population risk factor-based treatment regimen and an individual risk factor-based treatment regimen were compared, and the associated benefits and costs were evaluated.

Methods
The treatment regimen guided by the population risk factors was defined as such, that every COVID-19 patient aged ≥65 years old, and/or with at least one of the pre-selected chronic co-morbid conditions will be given a 500 mg/8 mL dose of the monoclonal antibody therapy, Sotrovimab intravenous, to prevent fatal outcome. The individual risk factor-based treatment regimen was determined using logistic regression model. We set the cost of Sotrovimab as $315.00 per patient, and the total cost including medication, hospital and infusion center administration charges, and charges for medical staffs as $2,000.00 per patient.

Results
Our study showed that the treatment regimen guided by population risk factors had resulted in a large amount of patient misclassification, with only 51.9% overall diagnostic accuracy, which is close to a random chance. However, by using the precision approach we developed for individual patient, the diagnostic accuracy was improved to 75%. Population risk factor-based treatment regimen prevented 1,570 more patients from a fatal outcome, however, it added 8 million dollars of cost for Sotrovimab and overall additional 54 million dollars of total cost.

Conclusion
Population level risk analysis provided inadequate information for individual patient’s diagnosis and treatment in clinical practice. Future research needs to focus on developing personalized diagnostic and treatment approach. We anticipate the improved clinical prediction by adding additional laboratory biomarkers to the individual precision diagnostic approach we developed.

Disclosures
All Authors: No reported disclosures
865. Same Shift Susceptibility Testing of Cefepime-Taniborbactam and Cefiderocol Using The Selux Next-Generation Phenotyping System
Authors: Jimenez David , Baker Kristin , Spears Benjamin , Flentie Kelly , Roberts Kristen , Michaels Gabriel , Stern Eric 
Published: November 2023

Abstract

Background
Robust, efficient, and reliable antimicrobial susceptibility testing (AST) systems are an integral component of effective antibiotic treatment. Multi-drug resistant (MDR) bacteria continue to emerge at alarming rates, requiring continuous innovation and development of new antibiotics. Among the new promising treatments for severe bacterial infections caused by carbapenem-resistant gram-negative bacteria, Cefiderocol (FDC) and Cefepime-Taniborbactam (FTB) have emerged as two frontrunners. FDC is the only FDA-approved siderophore cephalosporin, and FTB pairs the fourth-generation cephalosporin Cefepime, with Taniborbactam, a novel beta-lactamase inhibitor. AST results are paramount when directing therapy for patients with MDR infections, yet there is an average 3-year delay between the approval of new antibiotics and 510k submissions for new agents on automated AST systems. This is typified by FDC, for which there are currently no FDA-cleared automated AST systems. Here we assess the accuracy of FDC and FTB AST results using the Selux Next-Generation Phenotyping System.

Methods
For both FTB and FDC susceptibility, AST was performed using the Selux AST system and compared to CLSI broth microdilution (BMD) reference method in either cation-adjusted Muller Hinton broth (CAMHB) or its Iron depleted counterpart (ID-CAMHB). FDC, was tested in ID-CAMHB across 44 total CDC AR-Bank carbapenem-resistant K. pneumoniae, A. baumannii, and P. aeruginosa species. 34 CDC AR-Bank Strains predominantly resistant (30/34) to Cefepime were used to assess FTB. For FDC Essential Agreement (EA) and Categorical Agreement (CA) relative to ID-CAMHB were determined according to FDA breakpoints. FTB breakpoints were based on FDA breakpoints for Cefepime. For both agents, a comparison of BMD and the Selux system was accessed by EA and CA.

Results
The Selux AST system produced MICs to FDC with an average accuracy of 98% EA and 98% CA in ID-CAMHB (Table 1). In FTB, the Selux AST system produced MICs with an average accuracy of 94% EA and 100% CA in CAMHB (Table 2).

Conclusion
These data demonstrate the ability of the Selux NGP system to provide accurate results for FDC and FTB. This is the first known demonstration of an automated AST system for these important new drugs.

Disclosures
David Jimenez, B.S., Selux Diagnostics: Employee Kristin Baker, PhD, Selux Diagnostics: Employee Kelly Flentie, PhD, Selux Diagnostics: Employee Kristen Roberts, BS, Selux Diagnostics: Stocks/Bonds Gabriel Michaels, n/a, Selux Diagnostics: Employee Eric Stern, PhD, Selux Diagnostics: Board Member|Selux Diagnostics: Ownership Interest
875. Development of a Cheap, Portable Assay to Rapidly Profile Resistant Bacterial Infections
Authors: Roach David , Bhattacharyya Roby P 
Published: November 2023

Abstract

Background
Antimicrobial resistant (AMR) bacterial infections pose a significant and growing health threat worldwide. The burden of these resistant infections is often most severe in lower income areas, where the medical infrastructure necessary for their diagnosis is lacking. The development of cost-effective and accessible diagnostic tools for the rapid identification of resistant infections in low-resource settings is crucial. Specific High-sensitivity Enzymatic Reporter Unlocking, or SHERLOCK, is a promising CRISPR-based system that can aid in the diagnosis of infections and support clinical decision making. Here, we present an assay termed BADLOCK (Bacteria and AMR Detection by SHERLOCK) that uses SHERLOCK technology to rapidly identify bacterial species and AMR genes on blood cultures.
SHERLOCK Schematic
Enzymatic activity of the Cas protein is turned on when the target gene is bound, which then activates reporter probes.

Methods
We combine isothermal amplification of gene targets with SHERLOCK-based detection into a single step, allowing for a streamlined workflow and a total time-to-detection of less than two hours. The assay targets the topA gene for species identification, which is highly conserved within species but has sufficient variability between them to allow for discrimination between even closely related pathogens. A panel of clinically important AMR genes, including CTX-M-15, mecA, and five canonical carbapenemases, is also targeted to provide information on resistance profiles.
BADLOCK Targets
Gene targets included in the BADLOCK assay.

Results
BADLOCK has high sensitivity and specificity for both AMR genes and species identification and leverages a lateral-flow platform to provide a simple visual readout. We are currently validating BADLOCK on a library of several hundred clinical isolates with known genetic backgrounds, including a large collection of carbapenem-resistant Enterobacterales, which are major contributors to the global burden of resistant infections.
Lateral Flow Assay Results
Lateral flow results. Strip 1 is the topA gene specific to K. pneumoniae. Strips 2-4 are AMR genes KPC, CTX-M-15, and MecA. Lane 5 is a positive control; lane 6 is a NTC with bottom banding. “+” and “-” symbols mark representative readouts.

Conclusion
We have developed an assay for the cheap, rapid detection of bacterial infections of the bloodstream capable of detecting common pathogens as well as a panel of AMR genes. Our work has the potential to improve the diagnostic landscape for resistant infections in low-and-middle-income countries, which would represent a major step forward in infectious disease treatment in these underserved areas.

Disclosures
All Authors: No reported disclosures
880. Diagnostic Testing Sample-Type Preferences: Results From An International Survey On SARS-CoV-2
Authors: Akbarzada Sumaira , Narayanan Nithya , Salzano Leah , Tobik Emily R , Megiel Sarah , Duni Craig , Choate Brittany , Harper Samantha S , Wyllie Anne L 
Published: November 2023

Abstract

Background
Diagnostic strategies rapidly evolved during the COVID-19 pandemic in response to the unprecedented worldwide testing demand. The public’s perception in regards to testing has also evolved. Testing remains essential for understanding the current state of the pandemic and directing efforts and resources. The purpose of this study was to better understand the public view regarding clinical sample types to inform future diagnostics development and surveillance planning.

Methods
To assess SARS-CoV-2 testing preferences, we distributed a Qualtrics survey via social media and email to connections in &gt; 100 countries. The questionnaire covered testing preferences and key demographic information. Python was used to analyze the raw data.

Results
From 03/30-11/30/2022, a total of 2,094 responses were received from Africa (22%), Asia (8%), Europe (22%), North America (27%), Latin America and the Caribbean (9%), the Middle East (7%), and Oceania (6%). Participants were 55% female, 44% male, and 1% non-binary and ranged in ages (18-24, 13%; 25-34, 27%; 35-44, 23%; 45-54, 16%; 55-64, 14%; 65+, 8%). Education level and employment was skewed with 52% holding a graduate degree and 26% holding a bachelor’s degree; 27% were scientists/researchers and 29% were healthcare workers. Assuming equal accuracy between COVID-19 test types, respondents most preferred oral sample collection and least preferred methods involving coughing. The most preferred sample collection method varied by region (nasal swab = Europe; oral swab = Africa, North America, Oceania; saliva = Asia, Latin America and the Caribbean). In the majority of regions, saliva based testing was the most preferred method by parents and guardians for their children.

Conclusion
This study identified a preference for oral sample types for the detection of SARS-CoV-2, with saliva collection from children preferred by parents. Large-scale, easily accessible diagnostic testing is vital for detecting, monitoring, and containing outbreaks of respiratory pathogens; utilization of oral sample types supports the feasibility of this, if individuals are then more likely to test. Results from this study should be considered when new testing practices are designed to encourage maximum participation from individuals and improve community health.

Disclosures
Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
881. Saliva-Based, Extraction-Free PCR Testing For The Detection Of Key Respiratory Pathogens
Authors: Allicock Orchid M , Lin Tzu-Yi , Fajardo Katherine , Yolda-Carr Devyn , Hislop Maikel , Wang Jianhui , Zuniga Denora , Platt William D , Tuohy Beth , Peno Chikondi , Wyllie Anne L 
Published: November 2023

Abstract

Background
Efforts to control and monitor transmissible infectious diseases rely on large-scale screening often impaired by logistically difficult or invasive sample collection. The use of saliva as a non-invasive sample type could alleviate bottlenecks encountered in mass testing strategies. Having extensively demonstrated saliva as a sensitive sample type for SARS-CoV-2 detection, we sought to validate the approach for other common upper respiratory tract pathogens.

Methods
We modified our RNA-extraction-free SARS-CoV-2 PCR test for multiplexed detection of four additional respiratory viruses (“SalivaDirect+”): influenza A/B, RSV, and hMPV, and singleplex detection of pneumococcus. Stability of detection was tested after storage of saliva from pathogen-positive patients at +4°C, room temperature (∼19°C) and 30°C for 72 hours. De-identified saliva samples were collected from consenting adults ≥ 18 years of age with respiratory symptoms, requiring nasopharyngeal-swab based SARS-CoV-2 testing at Yale Health, New Haven, CT, USA. Saliva samples from individuals testing nasopharyngeal-swab negative for SARS-CoV-2 at the clinical laboratory were stored at -80°C until further processing in the research laboratory.

Results
We confirmed the limit of assay detection at 4 copies/µl for each target. We confirmed pathogen detection remained stable at +4°C, room temperature and 30°C for up to 72 hours. From the symptomatic testing site, 804 nasopharyngeal swabs tested negative for SARS-CoV-2; their paired saliva samples were tested with the SalivaDirect+ assay. Of those, 17 (2.1%) tested positive for one of the viruses targeted (influenza A, n=7; RSV, n=4; hMPV, n=6). No samples tested positive for influenza B. For influenza A and RSV, detection by SalivaDirect+ was comparable to testing following RNA extraction but detection of hMPV was less sensitive, even following assay modifications. In singleplex testing, 87 (10.8%) samples tested positive for pneumococcus.

Conclusion
We expanded a low-cost, open-source saliva-based PCR test for detection of other common respiratory pathogens. By testing saliva samples from symptomatic, SARS-CoV-2-negative adults, we detected common respiratory viruses which were otherwise missed in testing focused solely on SARS-CoV-2.

Disclosures
Anne L. Wyllie, PhD, Co-Diagnostics: Board Member|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
928. Concordance with Institutional Guidelines for Letermovir Cytomegalovirus Infection Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients
Authors: Peterson-Weber Alex , Palisano Nicholas , Alonso Carolyn D 
Published: November 2023

Abstract

Background
Cytomegalovirus (CMV) is an opportunistic infection in immunocompromised patients associated with significant morbidity and mortality. Letermovir (LET) is used for prophylaxis for CMV-seropositive allogeneic hematopoietic stem cell transplant (HSCT) recipients. An institutional guideline was developed to provide guidance on the appropriate use of letermovir. The purpose of this study was to determine overall concordance with letermovir institutional guidelines and to identify areas for quality improvement.

Methods
Our evaluation included adult hospitalized patients admitted from November 2019 to July 2022 for allogeneic HSCT who received LET, identified via medication administration records. The primary outcome was concordance with the institutional guideline criteria for use, as outlined in Figure 1. Secondary outcomes included incidence of breakthrough CMV viremia, use of concomitant HSV prophylaxis, and appropriate management of drug interactions (Figure 1).

Results
We identified 41 patients who received LET during the study period. After excluding patients who received a solid organ transplant, 32 patients were included in the study. The median time to LET initiation post-transplant was 7 days and the median time to discontinuation was 105 days post-transplant. Overall, 9 patients (28%) were fully concordant with our guidelines. Of the remaining patients, reasons for discordance are summarized in Table 1, mainly driven by continuation of LET &gt;110 days post-transplant (n=12, 37%). Three (9%) patients received LET despite CMV recipient negative serostatus (CMV R-). Breakthrough CMV viremia occurred in 3 patients (9%). All patients received concomitant HSV prophylaxis and had drug interactions managed appropriately.

Conclusion
Our evaluation identified a lower than expected rate of letermovir guideline concordance, primarily related to the recommended duration of drug therapy. We found that our guideline has supported providers to ensure that concomitant HSV prophylaxis is given and drug interactions are managed appropriately. A further investigation into the use of letermovir in CMV R- subjects and a cost analysis is planned to guide future institutional guideline updates.

Disclosures
Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support