bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-2223. Plasma Microbial Cell-free DNA Next-generation Sequencing can be a Useful Diagnostic Tool in Patients with Osteoarticular Infections
Authors: Petri Francesco , Mahmoud Omar , Ranganath Nischal , El Zein Said , Igwilo-Alaneme Rita , Abu Saleh Omar M , Berbari Elie , Fida Madiha 
Published: January 2025

Abstract

Background
The introduction of shotgun metagenomic sequencing (sMGS) methods that identify the presence of microbial cell-free DNA (mcfDNA) in peripheral blood have shown promising results in various populations of patients. There is a pressing need to evaluate its application for osteoarticular infections (OAIs) in real-world setting.

Baseline characteristics of the patients with suspected osteo-articular infections, including demographics, clinical characteristics, diagnosis, and KT results.

Methods
We retrospectively collected data on 73 adult patients who presented to the Mayo Clinic with suspected OAIs between 2019 and 2023, and for whom mcfDNA sMGS (Karius®, KT) testing was part of their diagnostic workup. We collected data on comorbidities, diagnostics, microbiological workout and its concordance with the KT. The primary objective was to evaluate its clinical impact on OAI diagnoses and management distinguishing into four categories: (1) KT was able to confirm an established diagnosis, (2) KT supported non-ID diagnosis, (3) KT established an unsuspected diagnosis, (4) KT did not add relevant information.

Relevant microbiologic studies of patients with unsuspected diagnoses established by the KT (N=5)

Results
In our cohort KT was performed in 73 patients (Table 1). Among the infected individuals, KT yielded positive results in 22/43 (51.2%) cases. Out of these 22 cases, 11 (50%) showed agreement with conventional diagnostic workup, while in five (22.7%) cases, the KT established an unsuspected diagnosis, improving the diagnostic power from 11/43 (25.6%) to 16/43 (37.2%) (Table 2). Moreover, yielded a negative result in 19/26 (73.1%) patients with non-infectious diagnosis (Figure 1). Native Vertebral Osteomyelitis (NVO) diagnosis (p &lt; 0.001) or OAIs with concomitant presence of endocarditis or endovascular infection (p = 0.005) were statistically associated with a definite, probable, or possible diagnostic certainty of KT result (Table 3). Overall, KT influenced antibiotic therapy in six cases (8.2%).
Table 3
Factors associated with diagnostic certainty categories

Conclusion
This is the first retrospective study aiming to assess the real-world usefulness of the KT on the clinical management of patients with OAIs, with a special focus on NVO. It underscores KT's real-world application in cases where traditional diagnostic methods fall short. In highly complex OAIs cases, KT added 11.6% to the diagnostic power by establishing unsuspected diagnosis in 5 of 43 infective patients. Patients with NVO or OAIs with concomitant endocarditis or endovascular infections particularly benefited from KT testing.
Figure 1
Distribution of KT results and their respective outcome according to the final diagnosis of suspected OAIs cases.

Disclosures
All Authors: No reported disclosures
P-2226. Clinical Validation and Performance of Molecular Syphilis Diagnosis by Loop-Mediated Isothermal Amplification
Authors: Smith Hayden Z , Sim Yijun , Kingma Jon , Wang-McGuire Ichih , Tantalo Lauren , Deveaux Khalil , Haynes Austin , Levin Greg , Sullivan Ka-Wing , Kwon Regina , Cookson Brad , Giacani Lorenzo , Salipante Stephen J , Lieberman Joshua 
Published: January 2025

Abstract

Background
Syphilis cases continue to increase rapidly in the US. Molecular detection of the pathogen, Treponema pallidum (TP) may speed turnaround time (TAT) and resolve ambiguous results from current diagnostics methods, which require stepwise serologic testing. Here we describe validation and clinical performance of a loop-mediated isothermal amplification (LAMP) assay for TP.

Methods
Candidate LAMP primers targeting the 23S rRNA locus of TP were evaluated and the best performing set was used for clinical validation per Clinical Laboratory Standards Institute guidelines. We determined the sensitivity, specificity, precision, accuracy, and reproducibility of the TP-LAMP assay in fresh and formalin-fixed tissue, body fluids, and whole blood using contrived specimens spiked with intact treponemes and residual clinical specimens. For whole blood, automated nucleic acid extraction was performed from 1mL ETDA-anticoagulated sample.

Results
The 95% limit of detection was determined to be 7-10 genomes/reaction by testing remnant DNA eluates spiked with TP gDNA. Assay specificity was evaluated by testing synthetic DNA targets representing non-cultivable targets and residual clinical samples containing DNA from 114 clinically relevant microbes, including non-TP spirochetes, bacteria, fungi, and viruses. TP-LAMP detected 100% of whole blood samples spiked with 120-125 organisms/mL; 88% of samples with 85 organisms/mL; and 80% of samples spiked with 60 organisms/mL.
From 09/2022 - 07/2023 TP-LAMP had 110 results in non-blood samples and the mean TAT was 4.7 days. Orthogonal diagnostic results were available for a subset of 34 samples. In this group the assay was 100% sensitive and specific with 7 positive tests, comprising 2 cases of primary and 5 cases of secondary syphilis. Three tissue specimens with negative TP-LAMP results had false-positive immunohistochemical TP stains due to cross-reactivity with commensal treponemes.

Conclusion
This assay represents a novel, clinically available method for sensitive and specific syphilis diagnosis. Additionally, the assay can resolve ambiguous findings in tissue. Applications in blood may aid in diagnosis of early or latent disease and resolution of unclear serologic test results.

Disclosures
Stephen J. Salipante, M.D. Ph.D., Anavasi: Grant/Research Support Joshua Lieberman, MD, PhD, Anavasi: Grant/Research Support
P-2228. Utility of Microbial Cell-Free DNA Next-Generation Sequencing for Evaluation of Vascular Graft Infection
Authors: Kerkelis Melissa , Ramesh Vaishnavi , Ranganath Nischal , Abu Saleh Omar M , Tabaja Hussam 
Published: January 2025

Abstract

Background
Vascular graft infection (VGI) is a rare but serious condition. Pathogen identification can be difficult given the deep-seated nature. Microbial cell-free DNA next-generation sequencing (mcfDNA NGS) is an emerging tool in non-invasive microbiologic workup. One commercially available mcfDNA is the Karius Test (KT). There is a paucity of data regarding utility and impact of mcfDNA NGS testing in the evaluation of VGI.

Methods
We retrospectively evaluated adult patients who underwent KT for evaluation of VGI at our institution. Only patients who met the Management of Aortic Graft Infection Collaboration (MAGIC) classification for suspected or confirmed VGI were included. We investigated the concordance between KT and conventional microbiologic workup. Conventional workup (CW) included pathogen identification through blood cultures, peri-graft/graft cultures, or histopathology. Concordance was defined by identical pathogen identification on KT and CW. We examined the influence of the KT result on clinical management.Figure 1.KT Results for Confirmed and Suspected VGI.

Results
We identified 25 patients who met criteria for either suspected or confirmed VGI per the MAGIC criteria. Microbiology was undefined in 8 patients who had negative KT and negative CW. A total of 17 patients had positive workup with 6 having positive KT and negative CW, 3 having negative KT and positive CW, and 8 having both positive KT and positive CW (Table 1). KT was less likely to be positive for patients who met criteria for suspected infection (4/10; 40%) as opposed to confirmed infection (10/15; 66.67%), albeit non-significant (OR 0.33, p=0.188) (Figure 1). The KT led to antimicrobial de-escalation in 27.3% of patients with positive CW and 35.7% of patients with negative CW (Figure 2). Full concordance of KT and CW was noted in 3 patients (Table 2).Figure 2.Influence of KT on VGI cases with positive and negative conventional work-up.
Treatment escalation was defined as the broadening of antimicrobial coverage due to KT results. Treatment de-escalation was defined as narrowing/discontinuation of antimicrobial coverage due to KT results.

Conclusion
We found that the positivity rate for KT was 56%. KT impacted management in 40% of cases. Patients with confirmed VGI had a higher likelihood of having a positive KT. KT was the only positive microbiological definitive test in one case. Further studies are needed to explore the utility and impact of KT in the workup of VGI.

Disclosures
All Authors: No reported disclosures
P-2251. The Infectious Complications After Belatacept-Use in Kidney and/or Pancreas Transplant Recipients
Authors: Abdi Abdinoor , Tarter Wyatt , Singam Hareesh V , Bregman Adam , Obeid Karam 
Published: January 2025

Abstract

Background
Conversion therapy substitutes belatacept (bela) for calcineurin inhibitors (CNI) after kidney and/or pancreas transplant (KT and/or PT). Investigations have yielded conflicting findings regarding the incidence of infections associated with bela- compared to CNI-use. This study explores the correlation between bela-use following KT and/or PT and the occurrence of fungal, CMV, EBV, and BKV infections, alongside mortality rates.

Methods
We included patients with a primary KT and/or PT between 1/1/2018 and 12/31/2022 and allowed for a 6-month follow up until 6/30/2023. We compared infectious outcomes in those who received bela at any time after transplant to those who did not. Cox proportional hazards models were used with bela as a time-varying covariate, and they were adjusted for gender, age at transplant, donor type, primary disease leading to transplant, CMV serostatus, and organ transplant type. Prentice-Williams-Peterson Cox models were used to examine the outcomes related to the recurrence of the viremia.

Results
We identified 558 unique KT and/or PT recipients, of whom 30 received bela after transplant as a conversion therapy. The mean (±SD) duration of bela was 19 months (±18) and 22 doses (±19). After bela-use, the adjusted hazard ratio [HR (95% CI)] for the first CMV, EBV, and BKV viremia in bela patients was 2.48 (1.08, 5.73; p&lt; 0.05), 4.30 (2.22, 8.34; p&lt; 0.05) and 1.01 (0.37, 2.75) times that of control patients, respectively. The HR for recurring CMV, EBV, BKV viremia was 1.54 (0.86-2.77), 2.71 (1.23, 5.97; p&lt; 0.05), and 0.45 (0.16, 1.21), respectively. The HR for fungal infections was 2.29 (0.52, 10.1) for bela patients. The HR for mortality was 4.14 (1.95, 8.79; p&lt; 0.05). An increase of age by a year was associated with higher mortality [HR 1.06 (1.03, 1.08; p&lt; 0.05)], and CMV [1.02 (1.00-1.03; p&lt; 0.05)], EBV [1.02 (1.01-1.03; p&lt; 0.05)], and BKV [1.02 (1.01-1.03; p&lt; 0.05)] viremia.

Conclusion
In this population of KT and/or PT recipients, bela-use as a conversion therapy is associated with a higher risk of mortality, CMV and EBV viremia, as well as recurrent EBV viremic episodes. Physicians should be especially vigilant when using bela for the older population.

Disclosures
All Authors: No reported disclosures
P-2253. Epidemiology and Outcomes of Gram-Negative Bacteremia in a Diverse Immunocompromised Population
Authors: Mostaghim Anahita , Hashem Nehal G , Pathan Sabina , Han Alison 
Published: January 2025

Abstract

Background
While gram-negative bloodstream infections (GN-BSI) carry significant risk of mortality and are of particular concern in neutropenic patients, relatively little is known about epidemiology and outcomes in contemporary immunocompromised populations. This study aims to assess the epidemiology of GN-BSI admitted to the National Institutes of Health Clinical Center (NIH CC).

Methods
Episodes of GN-BSI were identified through positive blood culture results from January 1 to December 31, 2023. Episodes not treated at the NIHCC were excluded. We performed chart review for baseline demographics, laboratory results, infectious disease consultation results, and clinical outcomes.

Results
Seventy-five episodes of GN-BSI admitted to the NIHCC were identified. All patients were immunocompromised by disease or treatment (Table 1). Forty-four (58.7%) were neutropenic at index culture with median duration of neutropenia 9 days after index culture (IQR 7-17.5) in survivors. Sixty-five (86.7%) had central venous access device (CVAD) and 16 (24.6%) were removed during the episode. Translocation (n=38, 50.8%) was the most frequently reported source followed by gastrointestinal (n=10, 13.3%) and pulmonary (n=9, 12%). Escherichia coli (n=25), Klebsiella pneumonia (n=17), and Pseudomonas aeruginosa (n=15) were the most frequently identified isolates. Twenty-one (28%) had polymicrobial bacteremia with 7 (33.3%) also containing a gram-positive isolate. Bacteremia duration was a single day in 64 (88.9%) episodes. Twenty-five (32.9%) had ICU admission and 7 (9.2%) experienced 30-day mortality. Neutropenic episodes had similar 30-day mortality (6.8% v 12.9%, OR 0.50, p=0.62) and ICU admission rate (OR 1.09, 0.37-3.28, p &gt;0.99). Polymicrobial episodes had similar 30-day mortality (4.8% v 11.1%, p=0.45). Those with CVAD removal had lower rate of ICU admission (12.5% vs 37.3%, OR 0.16, p=0.03) and lower 30-day mortality (0% v 11.9%, p=0.22) though not statistically significant.

Conclusion
Enterobacteriaceae caused most of GN-BSI at an institution with a diverse immunocompromised population. CVAD removal remains important in the treatment of GN-BSI. Neutropenia is not associated with worse outcomes.

Disclosures
All Authors: No reported disclosures
P-2254. Incidence, Clinical Characteristics and Outcomes of Heart Transplant Patients with Mucormycosis Infection: A Systematic Review and Meta-Analysis
Authors: Auyeung Austin , Gargaritano Kristine-Lou , Doyle Frank , Thomas Sanil 
Published: January 2025

Abstract

Background
Mucormycosis confers high morbidity and mortality in the immunocompromised population due to its rapid angio-invasive nature. Of note, this group of people includes those who have undergone solid organ or stem cell transplants, many of whom are placed on chronic immunosuppressive regimens. Mucormycosis incidence and clinical outcomes have been studied in bone marrow, lung, liver and kidney transplant recipients but not in heart transplant patients. Thus, our aim with this systematic review and meta-analysis is to characterize the incidence as well as clinical outcomes of Mucor infections in heart transplant recipients.Figure 1.PRISMA Flowchart

Methods
This study was registered with PROSPERO. Electronic databases Google Scholar, PubMed, Embase, Scopus and CINAHL were searched from inception up to 1 February 2024 for peer-reviewed articles of heart transplant patients who contracted mucormycosis. The primary and secondary outcome measures were incidence of mucormycosis infection and times to onset of infection and mortality, respectively. For statistical analysis, overall meta-analytic incidence was estimated using the user-written metaprop_one[FD1] [m2] command in Stata 15.1.Table 1.Species Identified in Infection

Results
Our search identified 296 studies, 88 of which underwent full-text review and 47 met inclusion criteria with 3916 total cases (Figure 1). Rhizopus was the most common pathogen identified causing mucormycosis infection (Figure 2). Pooled incidence of mucormycosis infection in heart transplant patients is 0.6% (95% CI 0 - 2%) across 12 studies (Figure 3). The majority of patients were male, 39/41 (95%) (Figure 4). Mucormycosis infection most commonly occurred during first 30 days post-transplant and decreased with time. Logistic regression analysis did not show significant association between time of infection post-transplant and mortality: Odds Ratio = 0.89 (95% CI 0.55-1.42, p = 0.616).Figure 2.Results of Meta-Analysis for Incidence of Mucormycosis Infection in Heart Transplant Recipients

Conclusion
Overall incidence of mucormycosis in heart transplant patients is 0.6%. Patients were more likely to contract the infection early (within 30 days) in the post-transplant period but there was no significant difference in mortality over time. The majority of affected patients were male and further studies are needed to determine if males are at higher risk of infection.Table 2.Demographics and Time of Infection Onset

Disclosures
All Authors: No reported disclosures
P-2262. Outcomes of Patients with Severe Persistent BK Polyomavirus DNAemia
Authors: Eichenberger Emily , Magua Wairimu , Karadkhele Geeta , Larsen Christian P 
Published: January 2025

Abstract

Background
BK polyomavirus (BKPyV) is the leading cause of polyomavirus associated nephropathy (PyVAN) in kidney transplant recipients (KRT). The goal of this study was to determine risk factors and outcomes associated with severe persistent BKPyV (SPBK).Figure 1A:Total estimated length of stay in a lymphocyte state: SPBK vs LBK

Methods
This is a single center, matched retrospective case control study of KTR with SPBK compared to 1) KTR with low/no BKPyV-DNAemia (LBK) and 2) KTR with high, transient BKPyV-DNAemia (HTBK). Definitions were as follows, SPBK: BKPyV load &gt; 6 log10 for &gt;90 consecutive days. LBK: BKPyV load remaining &lt; 3 log10. HTBK: BKPyV load &gt;4 log10 for &lt; 90 consecutive days, all within the first 2 years post-transplant.
SPBK were exact matched 1:3 to LBK controls on race, sex, donor type immunosuppression protocol, and genetic matched with robust Mahalanobis distance on age. SPBK cases were exact matched 1:2 with HTBK controls on race, gender, immunosuppression protocol, and genetic matched with robust Mahalanobis distance on age and donor type.
Differences between case and control groups were analyzed using Wilcoxon-rank sum test and Fisher’s exact test. A multistate Markov model was used to evaluate whether time spent in a state of lymphopenia (&lt; 1,000 cells/µL) was associated with SPBK.Figure 1A:Total estimated length of stay in a lymphocyte state: SPBK vs HTBK

Results
20 KTR with SPBK were matched to 60 LBK and 40 HTBK. Significantly more SPBK experienced acute cellular rejection within the first 2 years of transplant relative to LBK (75% vs 27%, p&lt; 0.001) and HTBK (22%, p&lt; 0.001). SPBK had a longer estimated duration of lymphopenia in the first 200 days post-transplant relative to LBK and HTBK (SPBK: 107.5 days, 95% CI 92.1, 122.7 vs LBK: 68.5 days, 95% CI 55.3, 84.8, vs HTBK 70.3 days 95% CI 58.8, 82.4, Figure 1A-B).
Median eGFR at 6 months post-transplant for SPBK was lower than patients with LBK and HTBK (44 vs 56, p=0.016; 44 vs 60, p=0.004, respectively). Burden of lab draws was significantly higher for SPBK vs LBK and HTBK (69 days vs 55, p&lt; 0.001; 69 days vs 56, p=0.006, respectively). Total cost of labs was $7836 for SPBK vs $4,691 for LBK (p&lt; 0.001) and $5922 for HTBK (p&lt; 0.001).

Conclusion
Patients with SPBK spent more time in a state of lymphopenia in the first 200 days post-transplant vs LBK and HTBK. SPBK is associated with worse renal function at 6 months post-transplant and is accompanied by a higher burden of lab draws and cost.

Disclosures
Christian P. Larsen, MD, PhD, Bristol-Myers Squibb: Advisor/Consultant|CareDx: Advisor/Consultant|Eledon: Advisor/Consultant
P-2266. Prediction of infection and acute rejection by QuantiFERON-Monitor in kidney transplant recipient
Authors: Rodrigues Costa Gisela Serra , Reusing Junior José Otto , Agena Fabiana Otto , Frade Vanessa Vidotto , David-Neto Elias , Pierrotti Ligia Camera 
Published: January 2025

Abstract

Background
Infection is an important complication after solid organ transplant (Tx), so a proper balance between rejection risk and reliable immune responses remains a challenge. One of approaches to evaluate net state of immunosuppression in Tx recipients is the measure of interferon-ɣ (INF-ɣ) release through QuantiFERON-monitor assay (QFM). This assay measures both innate and acquired immune responses. This study aimed to assess the association of QFM with infection and acute rejection (AR) occurring in the first-year post-Tx in kidney transplant recipients (KTR) cohort.
Box Plot of QFM results according to study timeline

Methods
Prospective cohort study of KTR who were given anti-thymocyte globulin (ATG) induction therapy enrolled in August/2018 to August/2019. QFM tests were collected at the Tx procedure (d0), 30 (d30), 90 (d90) and 180 (d180) days post-Tx and results were presented as medians of INF-ɣ values. Infections were classified in severe (hospitalization), opportunist, bacterial and clinically significant cytomegalovirus events. AR was biopsy proven or defined by treatment with ATG or corticosteroids.
Kinetics Plots of INF-ɣ stratified by Infection episodes and study timeline
A - Medians and interquartile ranges of INF-ɣ release according to study timeline and Severe Infection. B - Medians of INF-ɣ release according to study timeline and Bacterial Infection and C - Medians of INF-ɣ release according to study timeline and Opportunist Infection

Results
There were 68 KTR, of those 50 had 99 infections, resulting in a cumulative incidence estimated at 73.5% (IC95% 54.6-96.9%) and an incidence density of 4.4 per 1000 Tx-days (CI95% 3.2-5.7). Additionally, there were 16 AR in 16 KTR, with a cumulative incidence of 23.5% (CI95% 95% 13-38%) and an incidence density of 0.77 per 1000 Tx-day (IC95% 0,44- 1,26). The plots depicting INF-ɣ kinetics revealed a significant decline in median values at 30 days post-Tx (p=0,000), followed by a recovery to pre-Tx values at 180 days post-Tx. We found a statistically significant association between QFM results at day 0 and severe infections occurring 30-90 days post-Tx and bacterial infections occurring 30-180 days post-Tx. Furthermore, there was an association between QFM results at d30 and opportunistic infections occurring 30-90 days post-Tx. QFM collected at day 0 also exhibited an association with AR during the first-year post-Tx (p=0,014).
Kinetics Plots of INF-ɣ stratified by Acute Rejection episodes and study timeline

Conclusion
Preliminary results confirmed a high incidence density of infection in this KTR cohort and suggested the potential value of QFM for risk assessment of acute rejection and severe, bacterial, and opportunistic infections in the first-year post-Tx when collected at day 0 and day 30 post-Tx.

Disclosures
All Authors: No reported disclosures