bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-2215. Intestinal microbiome and metabolome fluctuations in patients receiving intensive chemotherapy for AML: Results from a pilot, prospective observational study
Authors: Imam Sabrina , Yates Samuel , Sulakhe Dinanath , Lin Huaiying , Sidebottom Ashley , Sundararajan Anitha , Moran Angelica , Adler Emerald , Roloff Gregory , Shah Syed , Rahmani Hamed , Saygin Caner , Stock Wendy , Lehmann Christopher , Pamer Eric , Nawas Mariam , Odenike Olatoyosi 
Published: January 2025

Abstract

Background
Loss of a diverse intestinal microbiome, particularly through the depletion of anaerobic bacteria, is associated with poor outcomes in people undergoing treatment for leukemia. We present preliminary results from a pilot, prospective observational study characterizing longitudinal changes in the fecal microbiome and metabolome in patients undergoing intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML).

Methods
We recruited 10 patients with newly diagnosed AML who were hospitalized for intensive chemotherapy. The subjects underwent daily serum and stool collections during the admission for induction chemotherapy and periodic serum and stool collections during subsequent admissions. Metabolome profiling was conducted by targeted GC- and LC-mass spectrometry of serum and stool specimens, and fecal microbiome composition was determined by Shotgun metagenomic sequencing. Clinical characteristics, including responses to chemotherapy and development of infections, were monitored.

Results
Metagenomic sequencing demonstrated marked variations in microbiome compositions between patients in our cohort. However, microbiome compositions and diversities remained stable within patients who maintained a higher prevalence of obligate anaerobes belonging to the Lachnospiraceae and Bacteroidaceae families. Moreover, despite stable microbiome compositions, we detected large fluctuations in fecal metabolite concentrations, particularly among secondary bile acids and conjugated and unconjugated bile acids, over the course of induction chemotherapy. Our results suggest that preservation of intestinal anaerobes enhances the stability of the microbiome over time, and the metabolic output of an individual’s microbiome is substantially impacted during cancer treatment.

Conclusion
Studying dynamics of the intestinal microbiome and metabolome during cancer therapy will help identify signals associated with microbiome diversity or disruption. We also plan to use broad targeted and untargeted platforms to identify metabolites in stool or serum that can be used as biomarkers to correlate with microbiome compositions and to identify patients who are at risk for adverse clinical outcomes associated with disrupted microbiomes.

Disclosures
All Authors: No reported disclosures
P-2217. Effect of Gut Bacterial Diversity on Mortality in Patients with Candidemia
Authors: Yoon Young Kyung , Park Seung Min , Park Soo Hyun , Suh Jin Woong , Kim Jeong Yeon , Sohn Jang Wook 
Published: January 2025

Abstract

Background
The gut microbiota plays an important role in defense against infectious diseases. However, only a limited number of clinical studies have investigated the microbiome in patients with candidemia. The aims of this study were to determine the nature of intestinal microbiome and to investigate the effects of gut microbiota on mortality in patients with candidemia.

Methods
This pilot study was conducted at a 1048-bed university-affiliated hospital in Seoul, South Korea, from November 2022 to February 2024. The study included adult patients (≥18 years old) diagnosed with candidemia. Total DNA was isolated from stool, and high-throughput sequencing was performed. Clinical data were collected from patient medical records. Multivariate logistic regression was used to identify the predictors of in-hospital mortality.

Results
A total of 55 patients were identified. The overall in-hospital mortality rate was 41.8%. The most commonly isolated Candida species was Candida albicans (36.4%), followed by Candida tropicalis (34.5%), Candida parapsilosis (18.2%) and Candida glabrata (7.3%). The most predominant bacteria species in their intestinal microbiome were Enterococcus species followed by Enterobacteriacea groups. The median Shannon diversity index [median (interquartile ranges); 2.4 (1.5-2.8) vs 1.6 (1.0-2.1), P = 0.015] and abundance-based coverage estimator (ACE) richness index [71.3 (39.3-97.7) vs 32.2 (15.6-61.2), P = 0.021] of the gut microbiota were significantly higher in survivors than in non-survivors. In a multivariate Cox regression analysis, septic shock [adjusted hazard ratio (HR) 8.8, 95% confidence interval (CI) 1.2-62.0, P = 0.030] and Shannon diversity index (adjusted HR 0.3, 95% CI 0.1-0.7, P = 0.012) were independently associated with the in-hospital mortality.

Conclusion
Our findings suggested that low gut bacterial diversity was independently associated with increased mortality in patients with candidemia. Exploring the variation of microbiome will potentially reveal new perspectives for the prevention and treatment of candidemia in the future.

Disclosures
All Authors: No reported disclosures
P-2222. Optimization And Performance Assessment Of A Novel Assay In The Diagnosis Of Early Lyme Disease
Authors: Bonelli Fabrizio , Rode Ashli , Zierold Claudia , Howard Jenny , Allen Nadia , Ghignoni Giorgio 
Published: January 2025

Abstract

Background
There is a need for sensitive clinical diagnostics for early and acute infection as current serology-based tests have low sensitivities in the early phases of the disease and cannot discriminate between acute and past infections. In 2016, using a 33 peptide T-cell stimulating cocktail (QIAGEN prototype), Callister et al. provided the first published evidence showing that the integration of humoral and cell mediated immunity can result in earlier detection of Lyme Disease. Additional data have since shown that interferon γ (IFNγ) release is a marker of acute disease and decreases following antibiotic treatment of the patients.

Methods
A fully automated chemiluminescence immunoassay was developed that allows the detection of IgG, IgM, and an IFNγ release assay component (QFL) using a proprietary peptide-based technology; an algorithm combines the 3 results into a POS, NEG or IND call. The performance of the assay was compared to standard two-tiered testing (sTTT) in a prospective clinical trial (NCT05041595).

Results
In 2021, 54 patients with sign and symptoms consistent with Lyme disease were evaluated, as well as 200 healthy subjects from an area of low Lyme incidence. The assay showed significant sensitivity improvement over sTTT (79.6% vs 57.4%). However, suboptimal specificity was observed (89.5%) with some relatively high IFNγ values that required reassessment of the test. A troubleshooting process identified two decorin binding protein peptides as being responsible for most of the non-specific reactivity of QFL. The performance of an updated assay version with a 31-peptide QFL stimulation tube was evaluated in 2022 on 56 patients with erythema migrans, and 99 apparently healthy subjects from endemic areas. Sensitivity and specificity were assessed and compared to sTTT and found to be 73.2% vs 58.9%, and 100% for both, respectively.

Conclusion
The data presented support the operational utility of the assay as an aid in the diagnosis of early Lyme disease, while providing high specificity after the optimization of the stimulation peptides of the QFL assay component. A promising expanded clinical validation study for the assay is in process for submission to the U.S. Food and Drug Administration.

Disclosures
Fabrizio Bonelli, PhD, Diasorin SpA: employee Ashli Rode, MS, Diasorin Inc: employee Claudia Zierold, PhD, Diasorin SpA: Advisor/Consultant Jenny Howard, PhD, QIAGEN: Employee|QIAGEN: Stocks/Bonds (Public Company) Nadia Allen, PhD, QIAGEN: employee|QIAGEN: Stocks/Bonds (Public Company) Giorgio Ghignoni, MD, Diasorin: Employee
P-2243. Multiplex PCR Pneumonia Panel in Critically Ill Patients Did Not Modify Mortality. A Cohort Study
Authors: Riaño-Sanchez Luisa Fernanda , Cortes Jorge , Álvarez-Moreno Carlos 
Published: January 2025

Abstract

Background
Severe pneumonia is a common cause of Intensive Care Unit (ICU) admissions. In critically ill patients, identification of the pathogen may allow timely adjustment of antibiotics and, therefore improve outcomes. The aim of this study was to assess whether performing a multiplex polymerase chain reaction (PCR) pneumonia panel in patients with pneumonia in ICU, has any effect on mortality, overall stay, ICU stay and duration of antimicrobial therapy.

Methods
A retrospective cohort study was conducted on adult patients with pneumonia who required ICU admission at 4 hospitals in Bogota Colombia, between November 2019 and June 2023. Patients who underwent multiplex PCR pneumonia panel testing were defined as exposed. Mortality at 30 days, length of hospital and ICU stay, duration of antibiotics and, their association with multiplex PCR pneumonia panel testing were evaluated using and Inverse Probability of Treatment Weighting (IPTW) to adjust for covariates and potential confounders. The infectious diseases specialist’s assessment and its effect on antibiotics adjustment was also determined.
Mortality analysis

Results
304 patients were included, 150 exposed, 154 non-exposed. Mean age 65.0 years (SD 14.6) and mean Charlson index 4.5 (SD 2.8). 186 (61.2%) patients had COVID-19 and 256 (84.2%) community acquired pneumonia. Length of hospital stay was 20.8 days (SD 17.0), ICU stay was 12.2 days (SD 10.9), total number of antibiotics administered was 2.7 (SD 1.7). No association was found between 30 days mortality and exposure HR 1.14 (CI95% 0.76-1.70), although infectious diseases specialist’s assessment is associated with a lower mortality HR 0.29 (CI95% 0.19-0.45). There was no association between exposure and antimicrobial therapy duration IRRa 1.17 (CI95% 0.90-1.54), hospital stay IRRa 1.02 (CI95% 0.75-1.38) or ICU stay IRRa 1.24 (CI95% 0.8-1.9).
Adjusted outcomes

Conclusion
The use of multiplex PCR pneumonia panel was not associated with changes in mortality, antibiotics duration, hospital or ICU stay. Integrating this type of testing into antimicrobial stewardship programs is necessary to contribute to more rational decision-making.

Disclosures
Jorge Cortes, MD, Pfizer: Grant/Research Support
Carlos Álvarez-Moreno, PhD, Pfizer: Grant/Research Support
P-2248. Modeling the Economic Impact of Different Testing Strategies for Meningitis/Encephalitis in Adult Patients from a US Hospital Perspective
Authors: Hasbun Rodrigo , Hueth Kyle , Paranhos-Baccala Glaucia , Timbrook Tristan T , Korrapati Lohit , Regan Catherine , Kwok Adrienne , Kirson Noam 
Published: January 2025

Abstract

Background
Meningitis/encephalitis (ME) is a life-threatening disease whose severity and trajectory vary by etiology. Many times, patients with suspected ME are unnecessarily hospitalized and treated with empiric therapy as a precaution while clinicians determine etiology. ME diagnosis and treatment algorithms vary across hospitals, with some using a battery of rapid diagnostic tests (RDTs) or syndromic testing to inform diagnosis and clinical decisions and others relying on bacterial culture and send-out tests. We modeled the economic impact of 4 ME testing strategies from a US hospital perspective.

Methods
A simulation model was used to generate a large sample of 20,000 suspected ME cases based on known distributions of ME etiology and cerebrospinal fluid (CSF) analysis results. The model simulated diagnosis, clinical decisions, and resource use and costs to hospitals in 4 testing scenarios: (1) no RDTs, (2) a battery of 4 RDTs for HSV, enterovirus, VZV, and C. neoformans/gattii, (3) BIOFIRE® FILMARRAY® ME panel alone [syndromic testing], and (4) syndromic testing in conjunction with RDTs for HSV and C. neoformans/gattii (Figures 1-2). Mean inpatient resource use (i.e., hospital stay and antimicrobial use) and cost per suspected ME case were estimated. Common costs across testing scenarios were excluded. Sensitivity analyses were conducted.

Results
The mean (95% CI) cost per suspected ME case was estimated at $19,337 ($19,150-$19,525) with no RDT use, $16,412 ($16,226-$16,598) with the battery of 4 RDTs, $15,465 ($15,285-$15,644) with syndromic testing, and $15,720 ($15,536-$15,903) under conjunction testing. Cost savings were driven primarily by reductions in hospital stay due to reduced time to correct pathogen identification. Performance characteristics of RDTs/syndromic test and time to correct pathogen identification had the largest impact on modeled costs for strategies that include RDT/syndromic testing.

Conclusion
Using either the battery of 4 RDTs or syndromic testing would result in cost savings for hospitals currently not using RDTs in ME diagnosis and treatment. Syndromic testing would yield even higher savings than the battery of 4 RDTs by further reducing unnecessary hospital stays and inappropriate antimicrobial use.

Disclosures
Rodrigo Hasbun, MD MPH FIDSA, Biomeriaux: Grant/Research Support|Biomeriaux: Honoraria Kyle Hueth, MS, MLS(ASCP)SC, bioMérieux: Stocks/Bonds (Public Company) Glaucia Paranhos-Baccala, PhD, bioMérieux: Stocks/Bonds (Public Company) Tristan T. Timbrook, PharmD, bioMérieux: Stocks/Bonds (Public Company) Lohit Korrapati, MBA, bioMérieux: Advisor/Consultant Catherine Regan, MPH, bioMérieux: Advisor/Consultant Adrienne Kwok, MPH, bioMérieux: Advisor/Consultant Noam Kirson, PhD, bioMérieux: Advisor/Consultant
P-2261. Belatacept-based immunosuppression does not confer increased risk of BK Polyomavirus -DNAemia relative to Tacrolimus-based immunosuppression
Authors: Eichenberger Emily , Magua Wairimu , Karadkhele Geeta , Fallahzadeh Mohammad Kazem , Vasanth Payaswini , Larsen Christian P 
Published: January 2025

Abstract

Background
BK polyoma virus (BKPyV) DNAemia imparts significant morbidity in kidney transplant recipients (KTR). It can lead to polyomavirus-associated nephropathy (PyVAN), impaired graft function, and graft failure. The effect of belatacept on BK polyoma virus (BKPyV) control remains largely unknown.

Methods
This is a propensity matched retrospective cohort study in adult kidney transplant recipients (KTR) transplanted between 2016-2020 who received a belatacept- versus tacrolimus-based immunosuppression regimen. A multi-state Markov model was used to evaluate BKPyV replication dynamics (BKPyV-dyn). Three BKPyV-dyn states were defined: BKPyV-dyn1 (viral load &lt; 3 log10), BKPyV-dyn2 (viral load &gt; 3 log10 and &lt; 4 log10), and BKPyV-dyn3 (viral load &gt; 4 log10).
Estimated total length of stay in a BKPyV replication dynamic state after evolution of the entire Markov process

Results
280 KTR on belatacept- and 280 KTR on tacrolimus-based regimens were compared. The probability of transitioning between BKPyV-dyn states and time spent in each state in both groups was comparable. Total duration in BKPyV-dyn-1 was 632.1 days (95%CI 612.1, 648.5) for belatacept vs 615.2 days (95% CI 592.5, 635.8) for tacrolimus, BKPyV-dyn-2 was 49.2 days (95% CI 41.3, 58.4) for belatacept vs 55.6 days (95% CI 46.5, 66.8) for tacrolimus, and BKPyV-dyn-3 was 48.7 days (95% CI 52.3, 79.5) for belatacept vs 60.9 days (95% CI 48.3, 76.4) for tacrolimus (Figure 1). Estimated mean sojourn time did (time spent in a given BKPyV-dyn state prior to transitioning to another state) did not differ by immunosuppression (Figure 2). BKPyV associated nephropathy (PyVAN) occurred in 3.9% in belatacept- and 3.9% tacrolimus-treated KRT (P &gt;0.9).
Estimated mean sojourn time by immunosuppression
Average single occupancy time in a BKPyV replication dynamic state

Conclusion
Collectively, our results indicate that relative to patients on tacrolimus-based regimens, patients on belatacept-based immunosuppression regimens do not require more frequent BKPyV QNAT monitoring or more aggressive immunosuppression reduction when BKPyV-DNAemia 3 log10 or greater is detected.

Disclosures
Christian P. Larsen, MD, PhD, Bristol-Myers Squibb: Advisor/Consultant|CareDx: Advisor/Consultant|Eledon: Advisor/Consultant
P-2273. Latent Tuberculosis and Strongyloidiasis Screening in Patients with Hematologic Malignancy Prior to Cytotoxic Therapy in Boston, Massachusetts
Authors: Reifler Katherine A , Smith Taylor Francoeur , Fagan Maura A , Bourque Daniel , Mark Sloan J 
Published: January 2025

Abstract

Background
Latent tuberculosis infection (LTBI) affects roughly one quarter of the world’s population and Strongyloides stercoralis (SS) affects approximately 100 million people worldwide. Individuals with hematologic malignancy receiving chemotherapy and systemic steroids are at increased risk of reactivation of LTBI and SS dissemination, which are associated with significant morbidity and mortality. However, LTBI and SS screening are not uniformly performed.

Methods
We conducted a quality improvement intervention of universal screening for LTBI and SS for one year (March 2023-March 2024) amongst patients initiating chemotherapy in the hematology clinic at Boston Medical Center, an urban academic safety net hospital with a large immigrant patient population. Screening was encouraged via integration into electronic medical record chemotherapy care plans and by lectures with hematology providers.

Results
876 pre-intervention and 83 post-intervention patients were included. Mean age was 61-63 years (pre- vs post-intervention groups). Plasma cell malignancy was most common (∼46%) followed by B-cell lymphoma (22-32%). Over 90% of individuals received systemic steroids, 2-3% were HIV+, and 2% were HTLV-1+. Between 33-40% of individuals immigrated from countries with high TB incidence rates &gt; 40 per 100,000 people and SS prevalence &gt;10%. The intervention increased LTBI and SS screening rates [TB: 337/876 (38%) pre- vs 49/83 (59%) post-intervention, SS: 159/876 (18%) pre- vs 49/83 (59%) post-intervention], but universal screening was not achieved. Among those screened for LTBI, 73/337 (22%) pre- versus 9/83 (18%) post-intervention were positive. Among those screened for SS, 4/159 (3%) pre- versus 2/49 (4%) post-intervention were positive.

Conclusion
These preliminary findings demonstrate a patient population with risk factors for reactivation and/or dissemination of LTBI and SS. Enhancing screening rates for LTBI and SS may prevent serious complications of these infections and there is a need to improve screening guidelines in these high-risk individuals.

Disclosures
Daniel Bourque, MD, Kephera Diagnostics: Grant/Research Support J. Mark Sloan, MD, Nuvectis pharmaceuticals: Advisor/Consultant
P-2274. Incidence and Microbiology of Postoperative Pleural Space Infections among Lung Transplant Recipients
Authors: Goodlet Kellie J , Nailor Michael D , Tokman Sofya 
Published: January 2025

Abstract

Background
Pleural space infections (PSI) represent a known complication of lung transplantation (LT) in the early posttransplant period. Within the historical literature, PSIs, and empyemas in particular, have been associated with an increased risk for death, with 29-43% 1-year mortality. However, these studies were small and conducted prior to advances in anti-infective prophylaxis and treatment strategies. Therefore, the purpose of this investigation was to characterize the microbial profile and outcomes of early PSI among lung transplant recipients (LTRs) within the modern era.Figure 1.Isolated organisms from pleural fluid of lung transplant recipients from present study (Panel A, 66 isolates, 2017-2022 transplants) and historical literature (Panel B, 4 studies, 55 isolates, 1983-2005 transplants)

Methods
This study was approved by the Institutional Review Board of St. Joseph’s Hospital and Medical Center (SJHMC). Included LTRs were transplanted between 2017-2022 at SJHMC with ≥ 1 pleural fluid culture positive for an organism within 90 days of LT. LTRs at SJHMC received cefepime, vancomycin, and levofloxacin in the immediate postoperative period, or targeted antibiotic therapy based on donor and recipient airway cultures. During the index transplant hospitalization, LTRs received prophylaxis with inhaled amphotericin and tobramycin. Additional opportunistic infection prophylaxis throughout the study period included valganciclovir, itraconazole, and trimethoprim/sulfamethoxazole.

Results
Among 554 total LTRs, 250 (45%) had pleural effusion cultures, and 54 (54/250, 22%) had ≥ 1 pleural culture positive for an organism (Table 1). Over 95% of effusions were exudative and 53% were neutrophil predominant. Of the 66 organisms isolated (Figure 1), 40 (61%) were Gram-positive bacteria, 21 (32%) were fungi (15 Candida species, 6 molds), 4 (6%) were Gram-negative bacteria, and 1 (2%) was unspeciated acid-fast bacilli. Infection was typically managed via effusion drainage and 4-6 weeks of pathogen-directed antimicrobial therapy. All-cause 1-year mortality was 7.4%, lower than national LTR 1-year mortality rates over the study period (∼10-12%).

Conclusion
In a large investigation of LTRs with early posttransplant PSIs, Gram-positive bacteria were isolated most frequently, with isolation of Candida also common. Gram-negative bacteria comprised a smaller proportion of infections than reported in prior literature. PSIs did not appear to predispose LTRs to poor posttransplant survival.

Disclosures
Michael D. Nailor, Pharm.D., InflaRx: Advisor/Consultant|Shionogi: Advisor/Consultant
P-2290. Pulmonary Nocardiosis in Renal Transplant Recipients From Pakistan: Risk Factors,Clinical Presentation and Mortality
Authors: Samar Rohama , Dodani Sunil , Nazmi Jawwad 
Published: January 2025

Abstract

Background
Nocardia is an opportunistic infection among renal transplant recipients (RTR) with an incidence of less than 1% but very high mortality. Data from Pakistan is scarce. Our aim is to find the risk factors, clinical and radiographic findings, antimicrobial sensitivity and outcome of Nocardia infection among renal transplant recipients.

Methods
All adult RTR diagnosed as Nocardia infection between 2013 and 2020 were included. The cases were matched with 1:2 controls based on sex, age (+/- 1 year), and transplant date (+/- 1 year). Risk factors, clinical features, antibiotic sensitivities and outcome were analyzed.

Results
A total of 48 patients developed Nocardia. Around 25% presented with disseminated disease. Median time since transplant was 2.68 years. High dose methylprednisolone and cytomegalovirus (CMV) infection within 90 days were independent risk factors for
Nocardia infection. The mortality rate was 20%. Central nervous system disease (CNS) and CMV infection within 90 days were significantly associated with mortality. The most susceptible drugs were co-trimoxazole and linezolid. Imipenem susceptibility was only 20%.

Conclusion
High dose methylprednisolone and CMV infection were independent risk factors for Nocardia infection. CNS disease is associated with mortality. Nocardia species were highly resistant to ceftriaxone and imipenem in our patient population.

Disclosures
All Authors: No reported disclosures