bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2085. Optimizing GAIHN-AR Network Microbiology Laboratory Assets for Early Detection of Carbapenemase-Producing Organisms in Limited Resources Settings: Argentine Experience
Authors: Corso Alejandra , Pasteran Fernando , Marchetti Paulina , Appendino Andrea , Pereda Rosana , Menocal Alejandra , Sangoy Ana , Kuzawka Marilina , Tocho Eugenia , Cioffi Antonela , de Mendieta Juan Manuel , Lucero Celeste , Colque Angel M , Alonso Laura , Iantorno Paula , Pagano Irene , Barcelona Laura
Published: January 2025

Background

The Global Action in Healthcare Network-Antimicrobial Resistance Module (GAIHN-AR), led by the U.S. CDC, enhances prevention, detection and response in low-resource hospital settings (LRS) against emerging antimicrobial resistance (AR) threats, with an initial focus on carbapenemase-producing organisms. GAIHN-AR includes a lab. component for improving early AR detection, an infection prevention and control program, and a communication platform for rapid response coordination. We describe the implementation verification/validation of new AR diagnostic methods and their integration into clinical workflow

Table

Methods

Prior to GAIHN-AR initiation in two hospitals in Argentina in January 2023, validation of CPO diagnostic techniques was conducted. For this, reference strains characterized by WGS from the CDC & FDA AR-Bank and Argentina-NRL repository were used. Evaluation followed manufacturer specifications, with GeneXpert also tested with alternative Dacron swabs. Pure colonies were used for validation of all methods, except for GENEXPERT®Carba-R where contrived fecal sample were also used. Methodologies were acceptable with sensitivity, specificity, and precision values ≥ 95%.The following methodologies were verified for carbapenemase detection in Enterobacterales, P. aeruginosa, and Acinetobacter spp. (ACI): (i) GENEXPERT®Carba-R; (ii) NG-Test®CARBA-5 lateral flow (ACI excluded); (iii) CHROMagar mSuperCARBA® chromogenic medium for carbapenem resistance detection; (iv) RAPIDEC® CARBA-NP. Additionally, the GENEXPERT®Carba-R was validated for: i) KPC variants with ceftazidime/avibactam resistance, ii) local circulation metallo-β-lactamase IMP variants

Results

The methodologies under evaluation achieved performance between 95-100%, except for the IMP variants with GenXpert Carba-R where sensitivity was reduced to 44% (Table).

Conclusion

Verification/validation process demonstrated that most methods had acceptable performance, allowing integration into lab workflows to facilitate prompt diagnosis and rapid communication with IPC teams. Results benefited not only GAIHN-AR hospitals but also other LRS facilities with whom they were shared through the NRL, offering valuable lessons for similar settings

Disclosures

All Authors: No reported disclosures
P-2086. The Clinical Profile of Patients with Indeterminate Xpert Rifampin Resistance Results in a Single Tertiary Level Institution
Authors: Tenorio Bettina Gabrielle V , Uayan Danielle Josefa F , Lumunsad Kriselle Felicia , Estuart Andrea S , Javier Jose Carlos Ruben R , Abad Cybele Lara R
Published: January 2025

Background

Tuberculosis (TB) is one of the leading causes of morbidity and mortality globally. Since the development of point-of-care tests such as the Xpert MTB/RIF assay, TB diagnosis has improved dramatically. However, the clinical profile of patients and significance of indeterminate rifampin resistance (RR) results remain unclear.Table 1.Clinical profile of Xpert RIF-Indeterminate patients

Methods

Hospital and TB clinic databases from January 1, 2016–April 30, 2023 were reviewed to identify patients with both Xpert MTB/RIF positive TB and indeterminate RR results. The electronic health record and paper charts of cases with indeterminate RR were then retrieved for detailed review. Relevant demographic characteristics and laboratory results were collected for analysis. Descriptive statistics was performed using SPSS.Table 2.Concordance of Xpert and culture rifampin resistance results

Results

Of 4339 records, only 31 cases (0.7%) fulfilled the criteria for study inclusion. The median age was 46 (range 22–97) years. Twenty-two patients were male (70.97%). The most common symptoms were cough (n=15, 48.39%), dyspnea (n=14, 45.16%), and malaise (n=10, 32.26%). Notably, only four had fever (12.90%). Four were asymptomatic. Majority were newly diagnosed TB (28/31, 90.32%) and had comorbidities (23/31, 74.2%), most commonly hypertension (n=15, 48.39%), diabetes mellitus (n=10, 32.26%), end-stage renal disease (n=3, 9.68%), and dyslipidemia (n=3, 9.68%). Eighteen patients reported alcohol use (58.06%). The most frequent chest x-ray findings were apical opacification (n=15, 48.39%), reticular or nodular infiltrates (n=9, 29.03%), and pleural effusion (n=7, 22.58%) (Table 1). Out of 31 patients, ten had rifampin-susceptible cultures (32.3%), two were rifampin resistant (6.4%), and the rest had unknown results (61.3%) (Table 2). Majority of patients were treated with standard 2HRZE/4HR regimen (28/31, 90.32%) and were alive (26/31, 83.87%) on the last follow up.

Conclusion

Majority of patients with Xpert MTB/RIF indeterminate RR results had clinical symptoms and radiographic findings consistent with active TB. Patients with indeterminate RR results can have either susceptible or drug-resistant M. tuberculosis on culture. Indeterminate Xpert MTB/RIF RR results should be interpreted with caution, and final results of TB culture should be followed up.

Disclosures

All Authors: No reported disclosures
P-2089. Transition of Lyme Serological Testing to the Modified Two Tiered-Testing Algorithm (MTTT): Observations from a Commercial Laboratory
Authors: Gillim Laura , Grover Ajay , Walworth Charles M , Alfego David
Published: January 2025

Background

2019 FDA clearance of Lyme disease serologic assays with new indications for use in a modified two-tiered testing (MTTT) algorithm marked the first significant change in Lyme serologic testing in over 20 years. In 2022 Labcorp® fully transitioned Lyme serological testing from the standard two-tiered testing (STTT) algorithm to the MTTT algorithm.

Methods

Retrospective analysis of results reported for Lyme serological testing March through October to correlate with warmer months consistent with tick exposure, comparing samples received in 2019 and 2021 assessed with the STTT algorithm and samples received in 2022 and 2023 with the MTTT algorithm. Algorithm interpretation was based on APHL guidance.

Results

In 2019 and 2021, a combined total of 314,409 individuals were tested from March through October using the Lyme STTT algorithm while a combined total of 597,142 individuals were tested in 2022 and 2023 using MTTT during the same time frame. The populations of individuals tested by STTT and MTTT did not differ significantly in sex (STTT: 57.2% female, MTTT: 57.4%), age (STTT: mean 51 ± 29.0 years, MTTT: 51.0 ± 30.0 years) or geographic distribution (by U.S. census bureau region). An overall increase in positivity was observed with the MTTT (6.4%) compared to the STTT (3.2%) and was specifically observed in the percentage of individuals with results consistent with recent or remote past infection (tier 1+/tier 2 IgG+ or both IgG+ IgM+). A decrease in the percentage of results consistent with acute or recent infection (tier 1+/tier 2 IgM+) was observed with MTTT (1.1%) versus STTT (1.5%). 11.6% of Lyme MTTT orders included a concurrent order for Lyme immunoblot. MTTT and immunoblot results were discordant for 9.1% of samples. Of the discordant samples 43% had detectable IgG and/or IgM on the 2nd tier MTTT but were negative by immunoblot.

Conclusion

The transition from the STTT to MTTT algorithm revealed higher rates of serological positivity for Lyme disease. Analysis of samples tested by both MTTT and immunoblot indicates that MTTT assays exhibit greater sensitivity, aligning with findings in peer-reviewed literature. Some clinicians ordered both MTTT and immunoblot tests, suggesting a need for education on updated Lyme testing recommendations.

Disclosures

Laura Gillim, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company) Charles M. Walworth, MD, Labcorp: Employee|Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company) David Alfego, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds (Public Company)
P-2091. Potential Impact of Targeted Sequencing on Central Line-associated Bloodstream Infection (CLABSI) at Stanford Health Care, 2015–2024
Authors: Rodriguez-Nava Guillermo , Egoryan Goar , Fu Kyle , Shepard John , McIntyre Karen , Sampson Mindy M , Salinas Jorge
Published: January 2025

Background

Central line-associated bloodstream infection (CLABSI) remains a key quality measure. However, the CLABSI surveillance definition attributes bloodstream infections in patients with central venous access devices to the central line if no other sources are found, potentially overestimating true line-related cases. Incorporating non-culture based microbiologic testing, such as next-generation sequencing, into the CLABSI surveillance definition may further skew these estimates. We aimed to review the organisms identified in 16S rRNA sequencing tests from blood samples to determine if they were typically associated with CLABSI.

Methods

We retrieved all 16S rRNA sequencing orders from Stanford Hospitals & Clinics from May 2015– May 2024. We identified orders obtained from blood specimens and categorized those patients with and without central venous access devices. We compared the identified organisms with those included in the NSHN CLABSI definition (https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf).

Results

Of the 3,830 16S rRNA tests ordered, 225 were from blood specimens. Among these, 40% (65/225) had a central venous access device at some point during admission. Eight tests were positive: two from patients with a device during collection, identifying Bartonella quintana and Ureaplasma urealyticum—both not excluded from the NHSN definition. Other positives included two cases of Borrelia hermsii, Paracoccus spp., Leptospira spp., Legionella spp., and coagulase-negative Staphylococcus, with only the latter typically associated with central venous access device infection. Only organisms from the genera Blastomyces, Histoplasma, Coccidioides, Paracoccidioides, Cryptococcus, and Pneumocystis are excluded from the NHSN CLABSI definition.

Conclusion

The increasing use of next-generation sequencing tests, such as 16S rRNA targeted sequencing, introduces unique scenarios where non-culturable organisms can be detected in blood specimens. There may be some risk of unfairly penalizing institutions for reporting organisms not associated with CLABSI. The list of organisms included in the NHSN CLABSI surveillance definition should be continuously updated to reflect the adoption of new non-culture-based testing methods.

Disclosures

All Authors: No reported disclosures
P-2094. Difference in Detection Rates of Coagulase-negative Staphylococci between BACTECTM FX (BD) and BACT/ALERT® VIRTUO® (bioMérieux)
Authors: Taylor Jeremy J , Whalen Allison , Colic Stephanie , Ozbolt Patrick , Antonara Stella
Published: January 2025

Background

Blood cultures (BCxs) with skin flora make interpretation of results difficult, impacting patient (pt) care on multiple levels. OhioHealth (OH), a large health care system in central Ohio, transitioned from BACTECTM FX (BD) to a new BCx detection system, BACT/ALERT® VIRTUO® (bioMérieux) in September 2022 and an increase in coagulase negative staphylococci (CoNS) isolates was noted. We compared detection rates of the most common contaminant, CoNS, between two BCx systems during 3 month pre-and post-implementation periods (March-May 2022 and March-May 2023).

Methods

BCx contamination rates were defined as CoNS in 1/2 sets as per microbiology laboratory standard procedures, or clinically as CoNS in 2/2 sets drawn simultaneously from the same site without signs/symptoms of infection. Pts were excluded if: i) pathogenic organisms were identified in prior BCxs (within 1 week of CoNS) or, ii) any organism other than CoNS was present in the same set. Pure CoNS BCxs were then assessed for number of sets positive (POS) on initial collection and follow up BCxs obtained after the first POS set with CoNS.

Results

From March-May 2022, 23,440 sets were collected with overall positivity rate of 9.5% (2,219 sets). CoNS was identified in 2% of total POS (465 sets). Of those, 244 pts had 1/2 initial sets POS resulting in 28% (69 pts) with redraws. In March-May 2023, 25,314 sets were collected with overall positivity rate of 10.1% (2,564 sets). CoNS was identified in 2.6% of total POS (657 sets). Of those, 364 pts had 1/2 initial sets POS with 37.9% (138 pts) with redraws. Pre-implementation, 55 pts had 2/2 sets POS for CoNS, and 5 pts grew the same organism on redraw. Post-implementation, 78 pts had 2/2 sets POS for CoNS, and 13 pts grew the same organism on redraw. Both periods had similar rates of 2/2 CoNS POS sets drawn simultaneously (72% and 70.5% respectively).

Conclusion

Increased rates of CoNS were detected after transition to the VIRTUO® system, including 1/2 POS sets, resulting in increased follow up cultures. Simultaneously timed sets of BCxs 2/2 POS with CoNS made interpretation of contamination difficult, highlighting the need for education on proper BCx collection techniques, including separate time/site draws to clinically assess true contamination events.

Disclosures

All Authors: No reported disclosures
P-2100. Comparison of Fosfomycin MIC Values between Parent and Inner Colonies (IC) of Escherichia coli Arising During Disk Diffusion (DD) Testing
Authors: Malik Khadijah , Salay Jenna , Bixby Morgan L , Bixby Morgan L , Collins Lindsey , Chang Tiffany , Hirsch Elizabeth B
Published: January 2025

Background

Recent studies have documented uropathogenic E. coli displaying the presence of IC during fosfomycin DD testing. These IC often demonstrate increased minimal inhibitory concentrations (MIC) when compared to their parent isolates. Investigating the clinical relevance of these IC and the extent of their resistance is a first step in determining whether they are associated with fosfomycin failure.

Methods

E. coli isolates (n = 69) collected from the University of Minnesota Medical Center (UMMC) that produced ≥ 3 discrete IC during at least one DD test were included. Parent and IC (n = 69) isolates underwent broth microdilution (BMD) testing using fosfomycin concentrations of 0.5-64 µg/mL for parent isolates and 8-1024 µg/mL for IC with incubation at 37°C for 16-20 hours. All susceptibility testing was supplemented with 25 µg/mL glucose-6-phosphate and conducted in duplicate on separate days. E. faecalis ATCC 29212 and E. coli ATCC 25922 were included as quality control strains. The results were evaluated using both CLSI (susceptible [S]: 64 µg/mL) and EUCAST (S: 8 µg/mL) breakpoints. Categorical agreement between the two guidelines were calculated.

Results

E. coli parent isolates had an MIC range of 1 to >64 µg/mL with a MIC50/90 of 8/32 µg/mL (Table 1). The IC isolates had significantly higher MIC ranges (< 8 and >1024 µg/mL) and MIC50/90 values of 256/ >1024 µg/mL. The parent isolates had 94.2% (n = 65) and 69.6% (n = 48) susceptibility per CLSI and EUCAST breakpoints, respectively. Using the more stringent EUCAST breakpoints, all IC isolates were resistant whereas 65.2% (n = 45) were considered resistant per CLSI breakpoints. Categorical agreement among the parent collection was 75.4% and 65.2% in the IC collection (Table 2).

Conclusion

Our data indicate IC arising from E. coli during fosfomycin DD testing are notably more resistant than their parent isolates, with an MIC50 increase of five, 2-fold dilutions. Future directions for this work include expanding the isolate collection and examining the fitness of these IC in comparison to their parents. Improving the understanding of the frequency, resistance, and fitness of IC arising from fosfomycin DD testing will help determine an optimal interpretation of IC, which may in turn improve patient outcomes.

Disclosures

Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, GSK: Advisor/Consultant|GSK: Honoraria
P-18. Incidence of Pneumococcal Disease and Vaccination Coverage among US Adults by Age and Risk Groups
Authors: Bailey M Doyinsola , Huang Yi-Ling , Ai Lei , Mohanty Salini , McGuinn Valina C , Johnson Kelly D , Cossrow Nicole
Published: January 2025

Background

Older adults and those with underlying medical conditions are at increased risk for illness, hospitalization, and death from pneumococcal disease (PD). The CDC currently recommends pneumococcal vaccination for adults ≥65 years and adults ≥19 years with underlying medical conditions who are at greater risk of PD. Identifying differences in pneumococcal vaccination coverage (VCR) and disease incidence is necessary to develop and implement strategies to improve VCR. We estimated VCR and incidence of PD, by age and risk group, among adults ≥18 years in the United States from 2017-2020.

Methods

This was a retrospective study of administrative claims data from Merative® MarketScan® Commercial Claims and Encounters Database. From 2017-2020, annual incidence rates of invasive pneumococcal disease (IPD), non-bacteremic pneumococcal pneumonia (NBPP) and all-cause pneumonia (ACP) were estimated by age group (18-49, 50-64, ≥65 years) and risk group (healthy, with chronic medical conditions (CMC) and with immunocompromising conditions (IC)) among adults with at least 2.5 years of continuous enrollment. Adults were considered vaccinated if they had at least one pneumococcal vaccine within 2 prior years to their index date. The percentage of pneumococcal vaccination was reported annually from 2017-2020.

Results

From 2017-2020, there were approximately 9-10 million patients annually in the study population. Less than 25% of US adults recommended for pneumococcal vaccination were vaccinated (Figure 1). Vaccination rates were highest among those ≥65 years (Figure 1). Annual incidence rates per 100,000 person-years decreased from 2017 to 2020 for IPD, NBPP and ACP (Figure 2). Each year, the incidence of PD was consistently higher among those ≥65 years, and those with IC or CMC. There was a decrease in the incidence of PD in 2020, coinciding with the COVID-19 pandemic.

Conclusion

Despite ACIP recommendations, vaccination rates remain low in those recommended to receive a pneumococcal vaccine, specifically among older adults and those with underlying conditions. This analysis underscores the opportunity to improve VCR and prevent PD in US adults, especially those at greatest risk.

Disclosures

M. Doyinsola Bailey, PHD, MPH, Merck & Co., Inc., Rahway, NJ, USA: Employee|Merck & Co., Inc., Rahway, NJ, USA: Stocks/Bonds (Public Company) Yi-Ling Huang, PhD, Merck: Stocks/Bonds (Public Company) Salini Mohanty, DrPH, MPH, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Kelly D. Johnson, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Nicole Cossrow, PhD, Merck: Stocks/Bonds (Public Company)
P-2107. Diagnostic accuracy of Nucleic Acid Amplification Tests for detection of Mycobacterium leprae in suspected leprosy patients from northern region of India
Authors: Yadav Rakesh , Saini Gurmeet , Kaur Manjot , Narang Tarun , Dogra Sunil , Sethi Sunil
Published: January 2025

Background

Leprosy is a chronic infectious disease, still remains a significant health problem in several parts of the world. A rapid and accurate diagnosis of the disease is essential for better management of Leprosy cases. In this study we compared three molecular methods i.e. PCR, Real TIME PCR and Loop-mediated isothermal amplification (LAMP) assay for detection of mycobacterium leprae.

Methods

A total of 114 samples were taken from 92 clinically leprosy suspected patients and contacts. DNA was extracted from the samples and molecular assays i.e. PCR, Real TIME PCR and LAMP was performed in parallel. Diagnostic accuracy of each test and Cohen's kappa coefficient was calculated using medcal online software.

Results

Among the 114 samples tested, the M leprae was detected in 35.09%(40/114), 34.2% (39/114) and 32.4%(37/114) by LAMP, conventional PCR, and real-time PCR, respectively. The overall agreement between conventional PCR and LAMP for detection of M leprae was 97.3% with a Cohen's kappa coefficient of 0.94, indicating perfect agreement. Similarly, the agreement between real-time PCR and LAMP for detection of M leprae was 97.3% with a Cohen's kappa coefficient of 0.94. However, the overall diagnostic accuracy of PCR, Real Time PCR and LAMP for detection of M leprae was 83.2%, 81.2% and 81.2%, respectively.

Conclusion

All molecular assays i.e. PCR, Real TIME PCR and LAMP had shown a similar diagnostic accuracy for detection of mycobacterium leprae.

Disclosures

All Authors: No reported disclosures
P-2108. Risk Factors for Indeterminate Tuberculosis (TB) Testing Results Among Immunocompromised Children in an Area of Low TB Endemicity
Authors: De Souza Randal , Hegde Shweta , Shimamura Masako , Dotson Jennifer L , Driest Kyla , McNicol Megan , Wise Kelly , Ouellette Christopher
Published: January 2025

Background

Tumor necrosis factor α inhibitors (TNFαi) are immunosuppressants used to treat autoimmune (AI) conditions and inflammatory bowel disease (IBD). TNFαi initiation requires tuberculosis infection (TBI) screening, often performed by interferon-γ release assays (IGRA) including the QuantiFERON Gold Plus (QFT) and T-SPOT.TB (T-SPOT). The rate of and risk factors for indeterminate (IND) testing results, as well as the optimal TBI screening assay, among immunocompromised children (ICC) with AI or IBD in an area of low TB endemicity remain poorly defined. We performed a retrospective analysis of QFT testing at our institution to identify rates of and risk factors for IND results. We also prospectively evaluated the performance of QFT versus T-SPOT in an area of low TB endemicity.

Methods

A retrospective analysis of children (ages 0-21 years) with AI or IBD on immunosuppression cared for at Nationwide Children’s Hospital (NCH) from 1/2010-12/2023 who underwent TBI screening with QFT. Patients were excluded if they had prior TBI, BCG vaccine, and organ or stem cell transplant. Demographic, laboratory results, and medication history were recorded. Prospectively, QFT-eligible patients were consented for concurrent testing utilizing the T-SPOT test, run in parallel. Single variable statistical analysis was performed.

Results

662 patients (372 (56.2%) male) had 2011 unique QFT tests performed. 148 patients (22.4%) had a total 191 (9.5%) IND QFT result at any time in the study interval. Younger age, lower absolute lymphocyte counts (ALC), and corticosteroid exposure at testing were observed more frequently in those with IND QFT results [TABLE 1]. At an interim assessment of the prospective study, 117 patients underwent tandem screening by QFT and T-SPOT; 5 total IND results were observed [QFT (n=4), T-SPOT (n=1)] [TABLE 2].

Conclusion

Younger age, lower ALC, and corticosteroid exposure at time of testing were observed more frequently in those with IND QFT results. While interim assessment of T-SPOT vs. QFT does not yield a difference, this may be driven by a high proportion of individuals with adequate disease control. Ongoing prospective assessment may better define an optimal screening IGRA assay for TBI among ICC with AI or IBD in an area of low TB endemicity.

Disclosures

Jennifer L. Dotson, MD, MPH, Pfizer: Grant/Research Support Christopher Ouellette, MD, Oxford Immunotec: Grant/Research Support|UpToDate: Royalties
P-2120. Clinical significance of 16S rRNA sequencing identification of Legionella species
Authors: Steenberge Laura , McBride Joseph
Published: January 2025

Background

Incorporation of 16S rRNA sequencing into clinical diagnostics has improved the ability of clinicians to diagnose fastidious bacteria and facilitates the identification of causative organisms in culture-negative infections. However, its clinical utility is unclear, with estimates of antimicrobial management changes from 16S identification ranging from only 4-15%. Legionella species are fastidious bacteria that can be difficult to identify without prior clinical suspicion, and thus can cause culture-negative infections that lead to 16S sequencing. However, Legionella are found ubiquitously in aquatic environments and its identification on 16S could represent a clinically significant infection, a nonpathogenic sample isolate, or a contaminant from sample processing or analysis. In this study, we reviewed 16S Legionella species results from our institution and determined whether they represented a clinical infection.

Methods

16S results from our institution were queried for Legionella species and a retrospective analysis of the resulting 10 cases was conducted. Multiple factors from the cases were assessed including demographics, comorbidities, type of 16S specimen, and antibiotic regimen change in response to 16S results. Additionally, we identified whether the 16S results represented clinically significant infections or contaminants.

Results

70% of the Legionella identifications were indicative of a clinically relevant infection. Specimens from a pulmonary source were much more likely to represent a true infection, while identifications from extrapulmonary sources were more likely to be a contaminant. The species of Legionella identified on 16S did not impact the likelihood of a true causative agent. The 16S results affected antimicrobial regiments in 60% of the cases and were often the only diagnostic test to point towards Legionella as a causative agent.

Conclusion

Legionella species identification on 16S can be an important diagnostic clue to the etiology of a patient's infection, but various clinical factors should be taken into account when assessing whether the result represents a true infection or contaminant.

Disclosures

All Authors: No reported disclosures
P-2125. Evaluation of MucorGenius® Mucorales Real-Time PCR Assay with Formalin-Fixed Paraffin-Embedded Tissue Specimens
Authors: Ganesan Anuradha , Sercy Erica , Leigh Carson M , Shaikh Faraz , Levine Tiffany , Campbell Wesley , Mende Katrin , Kiley John L , Bialek Ralf , Tribble David , Wickes Brian
Published: January 2025

Background

Early identification of mucormycetes in trauma-related invasive fungal wound infections (IFI) improves outcomes. A commercially available, multiplex, real-time Mucorales assay has the potential to provide results within 3 hours, hence we examined the performance of this assay.

Methods

Formalin-fixed specimens from combat injured that were positive for fungus on histopathology and mucormycetes on sequencing were examined using the PN-700 MucorGenius® assay (PathoNostics B.V, Maastricht, The Netherlands). The assay targets a conservative pan-mucormycetes sequence of the genera Rhizopus, Mucor, Lichtheimia, Cunninghamella, and Rhizomucor. For this analysis, we used a BioRad CFX96 Real-Time PCR Detection System with a positive detection limit of quantitative cycles (Cq) ≤ 30. Control specimens negative for fungus on histopathology and culture were obtained from trauma and non-trauma patients (N=2). MucorGenius® assay and sequencing results were compared.

Results

For this analysis, 31 patients contributed 63 specimens. Fungi of the genus Apophysomyces or Saksenaea were identified in 70% (Table 1). Using sequencing as the reference, Mucorales fungal DNA was detected in 58 specimens with the MucorGenius® assay with 5 false-negative findings (sequencing positive for Apophysomyces elegans [N=3], Actinomucor elegans [N=1], and Mucor spp. [N=1]), resulting in 92% sensitivity (95% confidence interval [CI]: 82-97%). There were no false positives (100% specificity; 95% CI: 16-100%; Table 2).

Conclusion

To our knowledge, this is the first assessment of the MucorGenius® assay with fixed tissue specimens in trauma-related IFI. When compared with sequencing in those with histopathologically proven fungal infections, the MucorGenius® assay was sensitive and specific. The assay also successfully amplified DNA of three genera that were not targeted by the panel kit (i.e., Apophysomyces, Actinomucor and Saksenaea). The potential for fast results with the MucorGenius® assay offers promise for rapid diagnosis of IFI. Further assessment of performance should be conducted using fresh and fixed specimens with suspicion of trauma-related IFI.

Disclosures

Ralf Bialek, n/a, InfectoPharm: Advisor/Consultant|InfectoPharm: Honoraria|InfectoPharm: podcasts|Sanofi-Adventis Deutschland GmbH: Advisor/Consultant|Sanofi-Adventis Deutschland GmbH: Honoraria|Sanofi-Adventis Deutschland GmbH: podcasts David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID Response
P-2127. Frequency, Interval, and Patient Factors Associated With Recurrence of Disseminated Cutaneous Coccidioidomycosis
Authors: Chow Nathan , Blair Janis E
Published: January 2025

Background

Coccidioidomycosis (cocci) is a fungal infection caused by Coccidioides and a common cause of community acquired pneumonia in endemic regions. Disseminated cocci occurs in ≤ 1% of persons with cocci, and among these, disseminated cutaneous coccidioidomycosis (DCC) is estimated to occur in 15 to 67% of cases, however little data exists to describe its frequency and timing of recurrence. Limited small studies show recurrence rates from 17 to 50% and often do not distinguish skin dissemination from other soft tissues. Our aim was to determine the frequency, timeframe and risk factors for relapsed DCC.

Methods

Potential cases of disseminated cocci were identified by ICD-10 codes 38.3, 38.7, 38.9 (& ICD-9 equivalents) and keyword-based search of pathology reports from 1/1/2008 - 3/31/2024. We included patients with proven or probable DCC. We excluded patients with primary cutaneous cocci or reactive rash. We performed a retrospective review to identify episodes of recurrence, comorbidities, and antifungal regimen.

Results

We identified 44 proven and 3 probable cases of DCC (33 males, 14 females), median age 48 years, 66.0% white, 21.3% black, 5.4% Hispanic. 18 (38.3%) were immunosuppressed and 6 (13.6%) had diabetes mellitus. Median follow-up duration was 68 months; 12 (25.5%) patients had ≥1 recurrence, 7 (14.9%) of whom relapsed ≥2 times. Median interval off of antifungals until recurrence was 14 months (range: 1 - 96). 3 (6.4%) patients had recurrence within three months of diagnosis, and 6 (13.0%) and 11 (23.9%) had a recurrence by the 1st and 5th follow-up year, respectively. 21 (87.5%) recurrences were at the same site as a prior occurrence, 4 (18.2%) occurred on antifungal therapy. There were no significant differences in recurrence rates by race or diabetes. Of the 18 immunosuppressed cases, there was 1 (5.6%) recurrence, though 14 (77.8%) continued antifungal therapy throughout follow-up.

Conclusion

Once antifungal treatment was discontinued, recurrence of disseminated cutaneous cocci was common, and among those whose DCC relapsed, multiple relapses were noted. Longer follow up is needed to better characterize the risk of long-term recurrence.

Disclosures

All Authors: No reported disclosures
P-2158. A Single Center's Utilization of Cell Free Microbial DNA Testing
Authors: Shaffer Alexander , Orner Erika , Thwe Phyu , Conway-Pearson Liam S , Szymczak Wendy , McCort Margaret E
Published: January 2025

Background

Metagenomic next generation sequencing techniques, either through targeted (tMGS) or shotgun sequencing (sMGS), have been shown to improve the odds of identifying a causative pathogen in a variety of disease states compared to conventional microbiologic testing. However, the high cost and unfamiliarity with MGS have led to questions on when and how these should best be used. We aimed to characterize the utilization of sMGS at a large urban academic hospital system, specifically the use of the commercial Karius test, a cell free microbial DNA (cfDNA) assay.

* conditions not mutually exclusive

Methods

We conducted a retrospective observational study through detailed chart review of the Karius tests sent from our hospital system from June 13, 2020, through April 10, 2024. Charts were reviewed for demographic, clinical and outcome information. Statistical analysis was performed using chi-square analyses.Figure 1:Pathogens with clinical additive diagnostic value (ADV)

Results

110 Karius tests from 104 unique patients have been sent from our institution since 2020. Most patients were immunocompromised (72.7%); see Table 1 for demographics. Patients received on average 13.4 days of antimicrobials before cfDNA testing was sent. An average of 6.5 blood cultures were sent, and in 69 cases, invasive procedures were performed before Karius testing was sought.

A pathogen was detected by Karius in 62 cases (56%). Results led to a change in antimicrobial management in 23% of cases. Karius had clinical additive diagnostic value (ADV) in 17 cases (15.6%), as defined by the detection of a causative pathogen that was not detected on conventional testing. Pathogens with clinical ADV are shown in Figure 1. There was no statistically significant difference between ADV, pathogen detection, or test concordance with conventional testing (p=0.71, p=0.64, and p=0.50 respectively) for cfDNA use in immunocompetent versus immunocompromised patients.

Conclusion

sMGS testing can provide clinically impactful results, although the optimal patient population and clinical scenario in which to employ these tests remains undetermined. Despite significant antimicrobial exposure prior to cfDNA testing, the Karius assay detected several fastidious pathogens that may not have been detected by conventional methods. Further research into ideal diagnostic utilization and stewardship of these tools is needed.

Disclosures

Wendy Szymczak, PhD, Quidel: Advisor/Consultant
P-2176. Validation of Air Sampling and Real-Time Quantitative Polymerase Chain Reaction for Measles Virus Surveillance: A Single-Center, Preliminary Assessment
Authors: Fricchione Marielle J , Nash Colleen B , Nguyen David , Barbian Hannah , Hayden Mary K
Published: January 2025

Background

During the early months of Chicago’s 2024 measles outbreak, many patients were admitted to local hospitals due to a lack of isolation housing in congregate settings. While the infection control potential of air sampling for viral pathogens is well described for viruses such as SARS-CoV-2, its utility for measles virus response is less clear. Here, we report a single center assessment of inpatient air sampling from airborne isolation rooms of patients with and without PCR-confirmed measles infection.Figure.Mean Measles Genome Copies in Four Rooms by Air Sampling Time

Methods

Aerosolsense samplers (ThermoFisher) were placed in 3 occupied and 1 unoccupied (negative control) airborne isolation rooms under negative pressure conditions. Air samples were collected at varying timeframes (30 minutes – 20 hours). Total nucleic acids were extracted from air samples within 24 hours of collection. Quantitative reverse transcription PCR (qRT-PCR) was performed to detect wildtype measles virus and genotype A (vaccine strain) measles virus; a gBlock DNA standard was included to estimate viral copy numbers. N450 amplification and Sanger sequencing were performed on selected positive samples to determine measles genotype.Table:Inpatient Measles Air Sampling Data at Different Time Intervals*per 5 μl cartridge nucleic acid extract, viral copies approximated using measles N1 DNA gBlock, ND: not done, UD: undetermined, NA: not applicable

Results

Air sampling methods were successful, with measles PCR positivity only in rooms with a measles. Measles patients were 2-3 days post rash onset. The air samples collected between 0.5 – 5 hours showed linearly-increasing measles viral load from 950-10,550 genome copies. [Figure] Samples collected at 20 hours did not show increased virus load compared to 2 hours, with mean 10,000 viral copies, indicating possible saturation over extended air sampling. Sequences derived from air samples were determined to be wildtype measles virus genotype D8 (the circulating genotype in Chicago at the time). [Table]

Conclusion

Air sampling in patient rooms allowed genotyping of measles virus in real-time and shows promise for describing the dynamics of measles viral load and potential for transmissibility. The utility of air sampling as a tool for measles surveillance and outbreak management warrants further testing in healthcare and congregate settings.

Disclosures

All Authors: No reported disclosures
P-2184. Antiviral Use among Immigrants with Chronic Hepatitis B (HBV) in Metropolitan-DC
Authors: Lin Christine , Dang Huong , Tang Lydia
Published: January 2025

Background

Globally, 296 million people are infected with chronic hepatitis B (HBV) and at risk for cirrhosis and hepatocellular carcinoma. In the Metropolitan-DC area, chronic hepatitis B infection (HBV) is 10 times more common in Asian, African, and Latin American communities (5% prevalence) than non-immigrants communities. Therefore, HBV-related liver disease, including cancer, is a major health disparity for immigrants. Antivirals reduce cancer risk but require long-term adherence. Immigrants face barriers to HBV antiviral adherence, including language, high cost of antivirals, and establishing care for HBV management. We examine antiviral use in a cohort of people with HBV.

Methods

HOPE is a natural history study at the University of Maryland, Baltimore. HOPE enrolls adults with HBV and includes TEMUL, a sub-study providing free tenofovir alafenamide (TAF) for 2 years. After completing 2 years of TEMUL, participants are transitioned to receiving antivirals through their non-study healthcare providers. We describe antiviral use while on TEMUL and at a 2-year follow-up.

Results

From May 2017 to March 2024, 92 people received TAF through TEMUL. Eighty-four were foreign-born (78 born in Asia and 6 born in Africa). Most (67%) had mild liver fibrosis at baseline. Eleven were withdrawn (3 lost to follow-up, 3 moved out of state, 5 voluntarily withdrew). Eighty-one completed TEMUL with sustained adherence to TAF. Fifty-eight completed a 2-year follow-up. At follow-up, 36 of 58 (62%) remained on TAF without interruption. Twelve (21%) switched antivirals because of insurance coverage. This caused lapses in antiviral use ranging from 1 month to 2 years in 5 (9%). Ten (17%) stopped antivirals due to loss of health insurance, high copay, and inability to follow-up with a healthcare provider. All 10 were foreign-born, Asian, and non-English speaking. Of these 10, 9 were viremic at follow-up and resumption of antivirals was clinically indicated in all.

Conclusion

Language and inadequate health insurance coverage hinder antiviral adherence in immigrants with HBV. Foreign-born, non-English speaking patients may be especially vulnerable to lapses in antiviral use. Interventions to improve access to antivirals tailored to this patient group are needed.

Disclosures

Lydia Tang, MBChB, Arbutus Biopharma: Grant/Research Support|Gilead Sciences: Grant/Research Support
P-2185. Community Health Worker-Led Intervention to Increase Hepatitis D Virus Screening among Immigrants in the Metropolitan-DC Area
Authors: Lin Christine , Nguyen Angeline , Byambaa Chooson , Galdamez Jennifer , Le Hai Chi , Ashford Sandra , Tang Lydia
Published: January 2025

Background

Hepatitis delta virus (HDV) is the most aggressive form of human viral hepatitis and coinfects people with chronic hepatitis B (HBV), increasing the risk of liver cancer. But HDV screening is not routinely done for people with HBV. In Metropolitan-DC, 5% of Asian, African, and Latino immigrants have HBV (10x the national rate). Therefore, these communities are at risk of HDV and would benefit from increased HDV awareness and screening. Health Betterment Initiative (HBI, an immigrant advocacy group) community health workers (CHWs) routinely assist immigrants with HBV and are well situated to deliver HDV education. However, little is known about the efficacy of CHW-led education interventions in these communities. We seek to evaluate an HDV education intervention aimed at increasing HDV screening in adults with HBV.

Methods

We developed an education intervention with HBI CHWs including educational programming, counseling, and printed materials. The post-intervention group (diagnosed from May 2023-May 2024) received the intervention and were surveyed 3-6 months after to assess HDV screening, knowledge, and usage of materials. We surveyed the pre-intervention group (diagnosed from April 2022-April 2023) to determine baseline HDV screening rate. Our primary outcome will be change in HDV screening from pre- to post-intervention. We present our lessons learnt so far.

Results

Since May 2023, HBI screened 2012 people and diagnosed 22 with HBV. All were from immigrant communities. So far, 18 pre- and 9 post-intervention surveys have been completed. Most were completed in Mongolian and Vietnamese. 20 were born in an Asian country, 6 in an African country, and 1 in El Salvador. Of the pre-intervention group, 4 (22%) reported HDV testing. All in the post-intervention group consulted doctors for HBV, and 1 reported HDV testing. Three recalled receiving our printed materials, but none used them at their doctor’s appointments.

Conclusion

Preliminary findings indicate good linkage-to-care for HBV, but low HDV screening and usage of our educational materials. More work is needed to customize education interventions for immigrant communities. We will use these lessons to consult with stakeholders to refine our intervention to improve engagement.

Disclosures

Lydia Tang, MBChB, Arbutus Biopharma: Grant/Research Support|Gilead Sciences: Grant/Research Support
P-2187. Emergency Department Patients’ Perceptions of the Seriousness of Hepatitis C – Implication on Improvement of HCV Care Continuum
Authors: Brown Dante , Mann Spencer , Cho Mun Heol , Haines Haley M , Winguth Patrick , Cammer Lauren , Peron Liz , Bouhsane Wassim , Hsieh Emma , Feezel Kevin , Riggan Benjamen , Dashler Gaby , Rothman Richard E , Hsieh Yu-Hsiang
Published: January 2025

Background

U.S. urban emergency departments (EDs) have identified thousands of individuals infected with hepatitis C virus (HCV) through their testing programs. However, significant challenges remain with linkage to care (LTC) rates from EDs at < 30%, representing the biggest drop-off along the HCV care continuum (HCV CC). Leventhal’s Common-Sense Model of Illness Representations, a framework to understand people's health brief and responses to illness, could help narrow that gap by defining key factors that contribute to self-perceived view of hepatitis C seriousness, and develop tools to improve the HCV CC.

Methods

Secondary data analysis of an ongoing randomized controlled trial of an individualized HCV educational web-based tool was performed. Patients presenting to an urban ED in Baltimore, Maryland from September 2022 to March 2024, ≥ 18 years, with a documented positive HCV Ab and no history of treatment (excluding those treated prior to reinfection) were eligible. The tool collected sociodemographic characteristics, historical healthcare utilization, HCV knowledge level, perceived barriers to care, and motivation level to care. Perceived seriousness of HCV was measured via an eight 5-point Likert scale which assessed perceptions of control, concern, awareness, and impact of HCV. Multivariable linear regression analysis was performed to determine factors associated with perceived seriousness of HCV.

Results

79 (87%) of 91 participants completed the baseline survey and were included for analysis. The majority were ≥40 years (71%), male (72%), or self-identified black (62%). Mean perceived seriousness of HCV was 3.2±0.7. A higher score was positively associated with the Black race, perceived barrier to HCV care score, and perceived motivation level for HCV care score [regression coefficient: 0.38±0.13; 0.30±0.10; 0.33±0.11, respectively; all p< .05] after adjusting for confounders.

Conclusion

We observed that amongst HCV-infected ED patients who were not currently engaged in care, there was an overall neutral perception of their HCV illness. Factors associated with higher score in perceived seriousness reflect current HCV and opioid intersecting epidemic and suggest there are mutable health systems issues that can be addressed.

Disclosures

Richard E. Rothman, MD, PhD, abbvie: Grant/Research Support|CEPHEID: Advisor/Consultant|CEPHEID: Grant/Research Support|CEPHEID: Honoraria Yu-Hsiang Hsieh, PhD, AbbVie: Grant/Research Support
P-2195. Hepatitis C Virus Screening Guidelines Rates Among a National Sample
Authors: Ferval-Shioya Kenta , Kaelber David C , Kerandi Allan M
Published: January 2025

Background

Objective:

Evaluate US hepatitis C virus (HCV) screening rates after the 2013 and 2020 US Preventive Services Task Force HCV screening recommendations.

Design/Participants:

A retrospective observational study utilizing TriNetX, an electronic health record (EHR) aggregation platform among 100 million patients.Table 1.Percentages of Patients Screened for Hepatitis C Based on Sample

Methods

We identified patients eligible for HCV screening based on their age (58-78 for 2013 guidelines and 18-79 for 2020 guidelines) and having a preventative care visit, based on common procedure terminology (CPT) codes. Successful screening encompassed a HCV antibody test result. High risk patients: encounter diagnosis ICD codes for HIV or renal dialysis or a CPT code for hemodialysis. We examined age distribution, gender, race, and ethnicity for possible screening disparities.Figure 1.Overview of Cohorts.

Results

In 2021, the first year after 2020 guidelines, 13.65% (219,333/1,607,333) of patients were screened. In 2022 and 2023, 15.25% (450,236/2,952,850) and 16.38% (638,335/3,896,376) were screened. In 2023, ten years after the 2013 guidelines, 22.66% (416,139/1,836,061) of eligible patients were screened. Among high-risk patients 10-year after the 2013 guidelines, 24.70% (62,332/252,402) with HIV and 25.80% (107,937/418,292) on dialysis were screened.

In our disparities analysis, we found that the percentage of unknown ethnicity or race, Asian, or other races was significantly less (p-value < .001) among screened eligible patients compared to eligible patients based on the 2020 and 2013 guidelines.

Over time screening disparities generally decreased so that people eligible based on the 2013 guidelines had fewer disparities in 2023 than those eligible based on the 2020 guidelines, except for gender where disparities increased between the two sets of guidelines with men being screened ∼3% more than women based on the 2013 guidelines.Figure 2.Total Eligible Patients and Eligible Patients Screened for HCV.

Conclusion

The current percentage of eligible patients screened for hepatitis C (< 20%) based on current guidelines is low and is only increasing slowly (1-2% per year). Even high-risk patients were only screened ∼25% of the time.Figure 3.Percentage of Eligible Patients Screened for HCV.

Disclosures

David C. Kaelber, MD, PhD, MPH, FAAP, FACP, FACMI, FAMIA, Dynavax Technologies Corporation: Advisor/Consultant