bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2200. Public Health Partnerships for Hepatitis C Elimination: Using Telemedicine and Syringe Service Program Hubs to Overcome Treatment Barriers in Rural Kentucky
Authors: Van Sickels Nicholas , Soria Jaime , Wilburn Amanda B , Collins Jana , Welty Kendal
Published: January 2025

Background

People who inject drugs (PWID) in rural areas of the United States face multiple barriers accessing Hepatitis C (HCV) care, including insurance-based treatment restrictions, long travel distances, and housing instability. The Kentucky Income Reinvestment Program (KIRP) provides harm reduction services, HIV and HCV testing, and linkage-to-care across most of Kentucky's Syringe Services Programs (SSPs). KIRP, in partnership with three high-prevalence counties (Figure 1) sought to reduce HCV treatment barriers by using SSPs as a hub for telehealth appointments, allowing for delivery of medications to the SSP, and providing inter-visit support to participants. We present early outcomes from this model and examine its effects on treatment initiation.

Methods

Advertising for the program began in McCreary County in June 2023, with Jessamine and Lee counties starting in January 2024. Patients were scheduled (or could walk-in) one weekday afternoon at each SSP. Visits were conducted via audio-visual (AV) telehealth, with KIRP staff present for support. HCV evaluation followed guideline-endorsed simplified pathways for those meeting criteria. Labs were performed at a 3rd party lab, and patients were followed using a minimal monitoring protocol.

Results

Between June 1, 2023 and April 30, 2024, 60 HCV seropositive patients were assessed, with 39 seen via AV telehealth. The median age was 39; 96% were White, 51% identified as cis-female, 93% were Medicaid recipients, and 34% reported unstable housing (Figure 2). Of 39 patients seen, 30 had labwork completed, 22 were RNA positive, and 18 initiated treatment. To date, ten patients completed treatment and one achieved SVR (Figure 3). Patients preferred to receive or house medications at the health department (78%). No significant effects of baseline demographics were found on the outcome of treatment initiation.

Conclusion

At baseline, less than a third of Kentuckians achieve a cure for HCV. Early findings from our intervention in three high-prevalence counties suggests the use of telehealth and an SSP hub can increase HCV treatment initiation and possibly completion for those who attend a visit. Further study of streamlined care delivery is needed to overcome HCV treatment barriers, especially in areas with limited healthcare access.

Disclosures

All Authors: No reported disclosures
P-2201. A Comprehensive Kidney Biomarker Panel to Assess Kidney Health after Hepatitis C Direct Acting Antiviral Therapy in Persons with HCV monoinfection and HCV/HIV coinfection
Authors: Perrone Lila A , Ma Yifei , Campos Kasey , Tse Warren , Tien-Smith Alexandra , Freasier Heather , Scherzer Rebecca , Estrella Michelle , Shlipak Michael , Tien Phyllis C
Published: January 2025

Background

Chronic Hepatitis C virus (HCV) infection is associated with greater risk of chronic kidney disease and proteinuria. We examined effects of 12 weeks of elbasvir/grazoprevir, an HCV NS5A inhibitor/NS3/4A Protease Inhibitor on glomerular filtration (creatinine, cystatin C), injury (albuminuria), and 9 novel kidney tubule biomarkers in adults with HCV infection over a 24-week period.Figure.Percent Change (95% Confidence Interval) from Baseline of Urine Kidney Tubule Markers 24 weeks after initiating Elbasvir/Grazoprevir in Patients with HCV

Methods

We included 36 participants with HCV (7 with HIV coinfection) from the San Francisco Bay Area. Urine biomarkers included kidney tubule function (α-1-microglobulin [α1m], β-2-microglobulin [β2m]) and injury (kidney injury marker-1 [KIM-1], neutrophil gelatinase-associated lipocalcin [NGAL], (interleukin-18 [IL-18]), fibrosis/repair (monocyte chemoattractant protein 1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) and synthetic function (epidermal growth factor [EGF], uromodulin [UMOD]). Biomarkers were measured at baseline, wk 12 (end of treatment), and week 24 (time of assessment for sustained virologic response [SVR]). We used linear mixed regression models with time as the main predictor to assess changes in kidney health, adjusting for demographics and urine creatinine.

Results

Over two thirds identified as Black/African American;89% were men and median age was 62 years. All but 2 achieved an SVR and 17% had advanced liver fibrosis using the FIB-4 serum marker. Median (interquartile range) for eGFRcr, eGFRcys, and urine albumin to creatinine ratio (ACR) were 82(63-100 ml/min),74(58-87 ml/min), and 10.4(4.9-24 mg/g), respectively at baseline. The percent (%) change from baseline for eGFRcr and ACR at weeks 12 and 24 was not statistically significant; eGFRcys was -11.4% lower (95%CI:-18%,-4.6%) at week 24. After 12 weeks of treatment, there were significant reductions in α1m, β2m, KIM-1, and MCP-1, with smaller reductions seen in most other markers (Figure). At week 24, these reductions were sustained for KIM-1.

Conclusion

Our findings suggest that HCV treatment with elbasvir/grazoprevir improves proximal tubule function and reduces cellular injury and fibrosis. Further research is needed to understand longer-term trends in kidney health following HCV cure.

Disclosures

Michelle Estrella, MD, Astra Zeneca: Board Member|Bayer: Grant/Research Support|Boehringer Ingelheim: Board Member Michael Shlipak, MD, Astra-Zeneca: Honoraria|Bayer: Grant/Research Support|Bayer: Honoraria|Boehringer Ingelheim: Honoraria Phyllis C. Tien, MD, MSc, Merck: Grant/Research Support
P-2205. The impact of pharmacist-driven transitions of care protocol in the treatment of hepatitis C infection
Authors: Chan Sophea , Cimino Christo , Ing Austin , Ereshefsky Benjamin , Bobbitt Laura , Moss Ryan , Muscarella Anahit
Published: January 2025

Background

Treatment for hepatitis C virus (HCV) can be delayed due to extensive documentation needed for insurance approval. Pharmacists can play critical roles in facilitating treatment approval, but the evidence regarding pharmacist-driven transitions of care protocols to facilitate HCV treatment approval and therapy initiation is limited. Therefore, we evaluated the feasibility and effectiveness of a pharmacist-driven transitions of care protocol for HCV treatment.

Methods

This was a non-randomized, prospective, single-center study at a large academic medical center. Adult patients admitted to the Infectious Diseases (ID) primary team were screened for HCV between 09/01/23 and 02/29/24. Exclusion criteria included decompensated cirrhosis, hepatocellular carcinoma, pregnancy/breastfeeding, current/prior HCV treatment, and transplant evaluation/receipt. Patients with HCV infection were offered treatment upon discharge at the outpatient ID clinic. Inpatient ID pharmacists performed pre-treatment workup and coordinated handoff to outpatient ID specialty pharmacists. Endpoints included treatment initiation and completion rates, time from screening to treatment initiation, and time from discharge to treatment initiation.

Results

Of 180 patients screened during the study, 13 (7%) were eligible for HCV treatment. The median age was 43 years, and 69% were male. More than 90% of patients were Caucasian and had a history of substance use disorder/injection drug use. Five patients (38%) were uninsured. Of the 13 patients, two had treatment approved, and one completed therapy. The remaining patients were lost to follow-up. The median times from screening to treatment initiation and from discharge to treatment initiation were 64 and 62 days, respectively.

Conclusion

This pharmacist-driven protocol resulted in inpatient screening of a large number of patients over six months and successfully identified 13 patients eligible to begin hepatitis C treatment after discharge. This is a novel approach to engaging patients in hepatitis C care. Despite facilitating transitions of care for these patients, the clinic no-show rate was unexpectedly high. Additional measures may be required to optimize treatment outcomes for this patient population.

Disclosures

All Authors: No reported disclosures
P-2208. Previously Diagnosed, Untreated Hepatitis C Among Emergency Department And Urgent Care Patients
Authors: Vinaithirthan Vall , Kamis Kevin , Hopkins Emily , Vaughn Shawni , Haukoos Jason , Rowan Sarah E
Published: January 2025

Background

Hepatitis C (HCV) incidence has been increasing steadily over the past decade despite the growing availability of well-tolerated, highly effective treatment. Additionally, many individuals who have been living with HCV for decades remain untreated. Emergency departments (EDs) serve large numbers of patients at risk for HCV who commonly do not have access to other forms of care. To address these gaps, innovative approaches to identification and linkage to care are needed. The goal of this study was to assess the number and characteristics of individuals with previously diagnosed but still untreated HCV presenting for acute, unscheduled episodic care, defined as ED or urgent care (UC) visits, in an effort to better understand the potential for HCV care interventions in these settings.

Methods

We performed a retrospective cohort study using electronic health record (EHR) data from Denver Health Medical Center in Denver, Colorado. ED or UC visits between January 1, 2019 and December 31, 2021 among those aged ≥ 18 years with evidence of HCV viremia at any time between January 1, 2016 and the day prior to the visit were included. We used descriptive statistics to characterize patient- and visit-level characteristics, timing of visits, and evidence of HCV clearance afterward.

Results

Over the 3-year study period, 1,407 unique individuals with evidence of current HCV infection were seen in the ED or UC, representing 5,829 total visits. At the patient level, the median age was 51 years (IQR 38-60), 53% were white, non-Hispanic, 29% Hispanic, and 73% cis-gender male. At the visit level, 17% were triaged as emergent status, 60% as urgent, and 16% less urgent. Visits were distributed relatively evenly throughout the week with Thursday being the most common day for qualifying visits (16%). Median length of stay for visits that did not lead to hospitalization was 276 minutes (IQR 153-461). Medicaid was the payer source for 73% and the most common chief complaints were related to substance use (18%) and pain (18%).

Conclusion

Substantial numbers of patients with previously diagnosed but untreated HCV are seen in the ED and UC annually, many of whom have Medicaid coverage. These healthcare locations may be ideal venues for addressing HCV through identification, referral to care services, and potentially treatment.

Disclosures

All Authors: No reported disclosures
P-2210. Perinatal Acquisition of Resistant E. coli Alters the Gut Microbiome in a Murine Model
Authors: Kremer Aspen N , Kremer Aspen N , Mithal Leena B , Sajwani Alima , Holm Johanna
Published: January 2025

Background

Maternal and neonatal colonization by pathogenic E. coli, particularly extended-spectrum beta-lactamase producing E. coli (ESBL-EC), heightens the risk of invasive infections in infants, complicating treatment and increasing morbidity. We developed a mouse model of perinatal transmission to explore this by first comparing the transmission rate among commensal E. coli strains, the pan-sensitive uropathogenic E. coli strain, UTI89, and four clinical ESBL-EC strains. We then determined the impact of early life acquisition of these strains on the mouse pup intestinal microbiome through sequencing analysis.

Figure 1

Proportion of pups colonized by each indicated strain, Sample sizes are for 24h and Day 7, respectively. The two control animals were not received no intervention.

Methods

Pregnant dams were inoculated with control or test strains one week prior to expected delivery date. Fecal pellets were collected and plated on selective agar to determine burden of colonization. Pups were born without intervention and sacrificed 24h or 7 days later, large intestines were collected, and bacterial transmission was quantified using selective agar. DNA was extracted and the V3-V4 region of the 16s rRNA gene was amplified for next generation sequencing.

Figure 2

Microbiome analysis was conducted on dam fecal pellets and pup large intestines. Mean relative abundance of top 26 taxa is shown for dam stool before birth, and 24h and 7-day old pup large intestines. Control is no dam manipulation, MG1655 and ST6438 are non-pathogenic, pan-sensitive E. coli and UTI89 is a pan-sensitive uropathogenic E. coli strain.

Results

While all strains adequately colonized the pregnant dam’s intestinal tract, only UTI89, ESBL-EC ST5, ST10, ST511, and the commensal ST6438 were transmitted to pups. ST511 and ST10 yielded colonization at both 24h and day 7 (Figure 1). Figure 2 shows the mean relative abundance of microbiota taxa in dam stool and pup intestines at 24h and 7 days old. As expected, pups born to dams colonized with E. coli had at least some Escherichia at 24h. However, at day 7, ESBL-EC ST10, ST511 and ST809 had higher Escherichia abundance than control strains, and all ESBL-EC strains had lower abundance of Ligilactobacillus, a common commensal, than the control strains. MG1655 and UTI89 pups had no Escherichia present by day 7. The ST511 pup data also suggests that ESBL-EC induced dysbiosis is not due to high maternal abundance and higher inoculation effect on pups, since Escherichia were not seen in a significant abundance in ST511 dams.

Conclusion

These results suggest that E. coli strains differ in their ability to perinatally transmit, and that ESBL-EC strains more often cause a sustained dysbiosis of the murine gut. Our ongoing work aims to understand the impact of this early life dysbiosis on neonatal development.

Disclosures

All Authors: No reported disclosures
P-2214. The Microbiome of Community-Dwelling Adults and Risk Factors for Colonization with Antibiotic-Resistant Bacteria in Chile
Authors: Rafael Araos , Ugalde Juan , Jara Alejandro , Sanchez Felipe , Rivas Lina M , Munita Jose M , D’Agata Erika M C
Published: January 2025

Background

Intestinal colonization due to antibiotic-resistant bacteria (ARB) often precedes episodes of infection and fosters the spread of antibiotic resistance. This study explores the clinical, epidemiological, and microbiome factors associated with ARB colonization in Chilean adults.

Methods

A cross-sectional study of 357 community-dwelling individuals from a community in central Chile was conducted between December 2018 - May 2019, using stool samples and health questionnaires. Stool samples were cultured on selective media, followed by identification with MALDI-TOF and disc diffusion susceptibility method. Fecal microbiome assessments were conducted using 16S rRNA gene sequencing performed on Illumina MiSeq. ARB colonization was defined as phenotypic resistance of recovered isolates to extended-spectrum cephalosporins, fluoroquinolones, and/or carbapenems.

Associations between colonization and clinical and epidemiological factors were analyzed through classification trees and logistic regression, while diversity and composition of microbiomes were compared between participants based on colonization status.

Results

No exposures were associated with the risk of ARB colonization. The microbiomes of colonized individuals featured Firmicutes, with Bacteroidetes, Actinobacteria, and Proteobacteria also present, paralleling the microbiome profile of the non-colonized individuals. However, ARB-colonized individuals had an overrepresentation of Escherichia/Shigella, Klebsiella, and Enterococcus genera. There were no differences in alpha or beta diversity by ARB colonization status.

Conclusion

The lack of risk factors regarding ARB colonization suggests that such colonization might occur without overt selective pressures. However, the overrepresentation of specific genera in colonized individuals could subtly indicate the influence of unrecognized selective pressures, such as environmental exposure to antibiotic residues. This scenario underscores the complexity of ARB dynamics and the need for further studies to explore potential environmental and indirect factors contributing to ARB colonization in the community setting.

Disclosures

All Authors: No reported disclosures
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

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

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

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

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

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

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 < 3 log10), BKPyV-dyn2 (viral load > 3 log10 and < 4 log10), and BKPyV-dyn3 (viral load > 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 >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

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 > 40 per 100,000 people and SS prevalence >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

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

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
P-2292. The Usual Suspect? Prevalence of Pseudomonas aeruginosa in Diabetic Foot Infections among Kidney Transplant Recipients
Authors: McCort Margaret E , Goyal Rohan , Burack Daniel A , Thwe Phyu , Ward Luz Liriano , Bartash Rachel
Published: January 2025

Background

Diabetic foot infections (DFIs) are a significant cause of morbidity in kidney transplant recipients (KTRs) with underlying diabetes. While empiric antibiotic coverage with an antipseudomonal antibiotic is common practice, recent studies of DFIs in non-transplant patients have found a relatively low prevalence of Pseudomonas aeruginosa (PSA). We hypothesize that the prevalence of PSA in DFIs is also low among KTRs.

Organisms isolated in cultures from diabetic foot infections (DFI) among kidney transplant recipients (KTR)

Methods

We performed a review of all positive microbiologic isolates from clinically relevant DFIs in KTRs requiring hospitalization at an urban transplant center from 1/2018-12/2023. All patients were > 18 years of age and underwent renal transplantation between 2015-2023. Patients could be included for more than 1 DFI if these occurred > 6 months apart or on non-contiguous sites. Patients without cultures or with cultures that yielded negative results were excluded. The primary outcome was the prevalence of PSA in microbiologic cultures, including bone, tissue, and fluid sources. The study was approved by our Institutional Review Board and results were reported using descriptive statistics.

Patient characteristics and demographics

Results

Forty-eight DFIs occurring in 40 KTRs were included. Median age was 62 and 83% (40/48) occurred in men. Average time from transplant to DFI was 1075.5 days. Additional demographic data is shown in Table 1. Eighty organisms were isolated with 42% (20/48) of infections being polymicrobial. PSA represented 5% of organisms isolated (4/80) and was present in cultures from 4 unique patients (10%). Streptococcus species and Staphylococcus aureus were the most commonly isolated organisms, representing 20% (16/80) and 29% (23/80), respectively. Among Staphylococcus aureus isolates, 47% were methicillin-resistant. Additional microbiologic data is shown in Figure 1.

Conclusion

The prevalence of PSA in DFIs was low among KTRs. Typical skin pathogens including Streptococcus species and Staphylococcus aureus were most common. While larger studies are needed to confirm these results, judicious use of antipseudomonal antibiotics should be considered in DFI management.

Disclosures

All Authors: No reported disclosures
P-38. Connecting the Dots: Unveiling Shared Motivations for Mpox Vaccination
Authors: Marshall Maurice , Heisler Shira , Kim Paul , Newman Gretchen , Touleyrou Lauren
Published: January 2025

Background

In 2022, a global outbreak of mpox spurred novel efforts for vaccination among previously unvaccinated individuals in the United States. Between 2022-2023, the United States was home to approximately 1/3 of documented global cases (32,063 cases) and suffered 56 deaths. These cases were concentrated in men-who-have-sex-with-men (MSM) and deaths were concentrated in people with HIV (PWH) and other immunocompromised individuals. Tolan Park Clinic in Detroit, Michigan, the largest HIV clinic in the state, began an intensive effort to vaccinate patients at risk of mpox acquisition. Surveys were provided to patients undergoing vaccination to assess motivations of undergoing vaccination. The objective of the study was to assess reasons for vaccination other than HIV status.

Methods

Surveys were conducted of patients at Tolan Park Clinic who underwent mpox vaccination. During the survey period, 167 surveys were completed. The survey evaluated different motivations to receive vaccination, including exposure to mpox in the last 14 days, attendance at an event with a known case of mpox, MSM or transgender women with greater than two partners in the last year, MSM or transgender women with a partner known to have a STI in the last year, if pt participated in commercial sex work, or plan to attend a ball, sex party, or bath house. Patients could select multiple responses to the survey.

Results

Analysis of results revealed that 49% (82) of surveys reported participants being MSM with greater than 2 partners in the last year as some motivation for undergoing vaccination. Following that, 24% (41) of surveys reported that participant planned to attend a ball, sex party, or bath house as a motivation for vaccination. The third most reported driver was MSM with a partner known to have an STI in the last year. This made of 14% (25) of all surveys reported.

Conclusion

Results demonstrated that the two most common drivers of vaccination included MSM with greater than two partners in the last year and those planning to attend a ball, sex party or bath house. Targeting vaccination efforts toward these groups helped to curb the spread of mpox. Our data will be utilized to better target outreach efforts during future epidemics of mpox.

Disclosures

All Authors: No reported disclosures
P-39. Trends in Pertussis Antibody Titers after DTaP Vaccination of Healthcare Workers at a Tertiary Children's Hospital in Japan
Authors: Furuichi Mihoko , Katsuta Tomohiro , Nakamura Yukitsugu , Suganuma Eisuke , Shimizu Naoki
Published: January 2025

Background

In Japan, diphtheria-tetanus-acellular pertussis (DTaP) is used for adults instead of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. DTaP vaccinations for healthcare workers in obstetrics and pediatrics have been recommended since 2019 in Japan. However, data on the prevalence rate of pertussis antibodies among health care workers are limited. This study aims to evaluate pertussis antibody titers before and after DTaP vaccination to establish an optimal vaccination schedule for healthcare workers.

Methods

This study was a prospective observational study targeting staff members who received DTaP vaccination at our hospital after 2019. We investigated age, gender, history of pertussis, and history of vaccination with pertussis-containing vaccines at the time of participating in this study. Anti-PT-IgG antibodies (EIA method) were measured once a year in the remaining serum from staff health examinations. We defined 40 EU/mL as the antibody-positive threshold.

Results

There were 1454 subjects, with a median (IQR) age of 33 (26-44) years and 349 (24%) were male. Twenty-one (1.4%) had a history of pertussis, and the reason for diagnosis was antibody testing in 8, symptoms in 7, and unknown in 6. Thirty-one (2%) received a pertussis-containing vaccine within 10 years at the time of participating in this study. Antibody positivity rates were 16% (194/1222), 42% (383/928), 35.3% (226/639), and 25% (105/416) before, one year, two years, and three years after final DTaP vaccination, respectively. Within 1028 seronegative subjects before vaccination, 25% seroconverted after vaccination; during 108 subjects of which who could follow their titer continuously, 48% maintained the antibodies for up to three years. In one case, the person did not seroconvert but developed antibodies up to 100 IU/mL two years after vaccination. During the study period, no pertussis cases were diagnosed, and no outbreaks were observed in our hospital.

Conclusion

In this study, 84% of Japanese healthcare workers did not have sufficient pertussis antibodies before DTaP vaccination. Following a single dose of DTaP vaccination, 25% showed positive pertussis antibody titers, of which 45% maintained effective antibody levels for 3 years.

Disclosures

All Authors: No reported disclosures