bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2198. High Prevalence of HBeAg negative among People Living with HIV and Hepatitis B ART naïve in Maputo - Mozambique
Authors: Chambal Lucia Mabalane , Nilsson Charlotta , Manjate Elias , Tchavana Corssino , Augusto Orvalho , Comiche Esperanca Sevene
Published: January 2025

Background

About 7.4% of the people living with HIV in the world are co-infected with hepatitis B virus (HBV), and more than 70% of the co-infected reside in Africa. HBeAg-negative chronic hepatitis B (CHB) is associated with persistent low viremia and progression into cirrhosis with a 3-10% yearly rate and with rare spontaneous remissions. We report the frequency of HBeAg among HIV/HBV coinfected recently diagnosed ART naïve patients.

Methods

We analyzed baseline data of a prospective cohort of newly HIV-diagnosed ART naïve patients at Mavalane Health Centre located in a periurban area in Maputo City. Between April 2021 and November 2022, all patients acove 18 years of age were enrolled then screened for HBsAg. All participants had CD4+ T cells count, further serological markers of hepatitis B (anti-HBc IgM, HBeAg, anti-HBe), HIV and HBV viral loads assessed using standard procedures. Quantitative variables were expressed as mean and standard deviation, whereas qualitative ones were expressed as frequency and percentage.

Results

A total of 1,106 participants were included, and HBsAg was reactive in 81 participants, yielding a co-infection rate of 7.3%. Being male (OR = 0.58 and 95%CI: 0.59 to 0.94) or sex worker (OR = 3.69, 95%CI: 1.10 to 10.58) was associated with being co-infected. Overall, 67/81 (80.2%) of the co-infected were HBeAg negative and 14/81 (19.8%) were HBeAg positive. The median APRI was 0.5 (IQR 0.3, 1.1) for the HBeAg negative and 0.7 (0.3, 1.4) for the HBeAg positive. The median HBV-DNA was 258.0 IU (IQR 10.0, 4,974.5) for the HBeAg negative and 746,287.0 IU (IQR 2,720.0, 49,899,213.0) for the HBeAg positive subjects (p < 0.001).Among the HBeAg negative 44 (65.7%) had a detectable HBV-DNA with 20 (29.9%) presenting with HBV-DNA > 2000 IU and 14 (20.9%) with a HBV-DNA > 20 000 UI. Two (3.0%) HBeAg negative participants and one (7.1%) HBeAg positive participants presented with hepatocellular carcinoma (HCC).

Conclusion

These results confirm the high prevalence of HIV and HBV co-infection in Mozambique and brings new data on HBeAg negative frequency. There is a need to test for HBV all HIV infected and integrate the management and monitoring of hepatitis B and liver disease-specific tests in public ART programs to predict and reduce the occurrence of HBV complications and mortality.

Disclosures

All Authors: No reported disclosures
P-2199. Empowering Healthcare Providers in the Appalachian Region to Manage Hepatitis C Infection: A Descriptive Study
Authors: de la Espriella Mariana Gomez , Peterson Christopher , Faulhaber Jason R , Ravagli Cara , Chitwood Crystal , Nowak Elizabeth , Rubio Marrieth , Baffoe-Bonnie Anthony
Published: January 2025

Background

Hepatitis C virus (HCV) infection disproportionately affects people living in Southwest Virginia, with low treatment rates exacerbating the issue furthermore. Rural residents face barriers like limited access to services and lengthy referral processes. Since January 2019, Virginia Medicaid has removed the restriction for primary care providers to manage HCV independently. To improve access to Hepatitis C treatment in our communities,we developed a concise, free training program aimed at empowering rural primary care providers in our health system to screen, diagnose, and treat HCV.

Methods

We invited Family Medicine (FM) practitioners from our health system in rural areas to participate. Offering a convenient seven-part video series led by infectious disease and gastroenterology specialists, alongside monthly webinars, patient resources, and hands-on coaching, we tailored the program to fit their busy schedules. Consultation with specialists and a dedicated treatment coordinator supported complex cases was also part of the program.

Results

Twenty-two FM providers, including 17 physicians and 5 advanced practitioners, engaged in the program. Within a month, HCV screening by program participants increased by 53%. Treatment initiation time decreased significantly from 178 days to 46 days compared to traditional specialist referral methods.

Conclusion

Our findings demonstrate that leveraging specialist knowledge through virtual training programs, coupled with remote support, significantly enhances HCV care accessibility. Shortening the time to treatment initiation, especially when managed by primary care providers, improves HCV detection and treatment outcomes in rural areas. This program represents a vital step towards addressing the Hepatitis C burden in underserved communities.

Disclosures

Cara Ravagli, PA, Gilead: Grant/Research Support
P-2225. Interactions between phage and host bacteria in immunized rabbit serum
Authors: Herren Sebastian , Karau Melissa J , Koscianski Christina , Christensen Trace A , Patel Robin
Published: January 2025

Background

Phage therapy is being evaluated to treat bacterial infections. Host-related factors that might abrogate phage efficacy remain incompletely characterized. Phage aggregation has been hypothesized to protect phages in harsh environments. Herein, effects of immunized rabbit sera on phage aggregation were assessed.

Methods

Three New Zealand rabbits were immunized weekly for 3 weeks by intramuscular injection of phage K. Serum samples were collected weekly at times 0, 7, 14, 21 and 28. Development of an antibody response was confirmed by ELISA. Phage K was exposed to immunized serum with or without heat-inactivated host bacterium (Staphylococcus aureus ATCC 19685) as follows. 45 µl of phage K (1010±1 plaque forming units/mL [pfu/ml]) was mixed with 5 µl immunized serum diluted 1:1000 with or without heat-inactivated bacterial host in phosphate buffered saline (PBS). After incubation, exposed phage was visualized using transmission electron microscopy (TEM, JEOL) at 80kV.

Results

Phage K immunization elicited a strong IgG response. Exposure to immunized serum led to a decrease in viable phage over time, abrogated by adding heat-inactivated bacteria (Fig 1). TEM imaging showed phage clustering with exposure to immunized serum (Fig 2A); clusters appeared disorganized with concomitant exposure to heat-inactivated host bacteria (Fig 2B). Exposure of phage to heat-inactivated bacteria without serum yielded evenly distributed phage, with minimal clustering (Fig 2C).

Conclusion

Phage K exposure elicited a neutralizing immune response associated with decreased phage survival in immunized serum, prolonged by adding heat-inactivated host bacteria. TEM imaging showed phage K clustering in different ways depending on the microenvironment encountered. Biological relevance and mechanistic underpinnings of these phenomena need further characterization.

Disclosures

Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria
P-2227. Real-Life Utilization and Clinical Impact of Karius Testing in Solid Organ Transplant Recipients: A Retrospective Analysis
Authors: Shah Jesal R , Rizwan Sohail M , Al Mohajer Mayar , Khalil Sarwat
Published: January 2025

Background

Metagenomic next-generation sequencing such as Karius test (KT), is increasingly being used for microbial detection in various clinical syndromes, including sepsis, Fever of Unknown Origin (FUO), pneumonia, and cardiovascular infection. However, data regarding the utility of KT in solid organ transplant recipients (SOTR) are lacking. There is a need to assess its clinical impact and appropriate use considering its cost, potential for detection of commensal organisms, and lack of antimicrobial susceptibility data. Our study focuses on the real-world clinical impact of KT in SOTR.

Methods

We performed a retrospective review of all adult SOTR who underwent KT at Baylor St Luke’s Medical Center from March 2017 to February 2023. Clinical impact (positive, neutral, and negative) was assessed using standardized objective criteria utilized in prior studies. Descriptive analysis with patient and clinical characteristics was completed.

Results

A total of 113 KT in liver (42%), kidney (35%), lung (20%) and heart (13%) transplant recipients were completed in the study period (Table 1). The most common clinical syndromes where KT was ordered included: pneumonia (36%), FUO (16%), and intrabdominal infections (15%). Majority (81, 72%) of the KT results were positive for microbiological organisms (Table 2). Overall, 52 (46%) of conventional microbiological tests (CT) were also positive. Ultimately, 27 (24%) of cases were identified with positive clinical impact from KT testing, 87 (77%) neutral, and 4 (4%) negative, respectively (Table 3).

Conclusion

In SOTR, KT can add a positive clinical impact and identify microorganisms beyond conventional microbiological testing across clinical syndromes. However, larger prospective studies are needed to define the optimal timing and utilization in diagnostic evaluation algorithms for syndrome-specific work-up in SOTR.

Disclosures

M. Rizwan Sohail, MD, Medtronic: Advisor/Consultant|Medtronic: Honoraria|Philips: Advisor/Consultant|Philips: Honoraria
P-2229. Comparative Evaluation of Multimodal Large Language Models with Vision in Infectious Diseases Cases with Clinical Images
Authors: Non Lemuel , Hodges Jacob
Published: January 2025

Background

Real-world patient scenarios often involve a composite of text and various clinical images. We explored the performance of advanced multimodal Large Language Models (LLMs) equipped with image-to-text models (vision) in diagnosing complex infectious disease cases containing both text and clinical images.Figure 1:Case #19003; Right foot cutaneous lesion [Photography]. Partners’ Infectious Disease Images; Accessed on April 4, 2024 from https://www.idimages.org/images/detail/?imageid=2356

A sample image from IDImages.org showing a physical exam finding and the descriptions from the AI chatbots.

Methods

We assessed the performance of two publicly accessible LLMs with vision—GPT-4 and Claude Opus—on a series of 25 complex infectious disease scenarios with 67 clinical images sourced from www.IDImages.org. Prompts were standardized for each case, including instructions to identify the diagnosis, generate differential diagnoses, and describe each image. The models' accuracy in identifying the diagnosis and including it within the differential diagnoses was evaluated using a binary scoring system (0 or 1). Image description quality was assessed using a Likert scale ranging from 0 to 2 comparing the models' outputs against provided descriptions (Figure 1). Scoring was conducted by two independent clinicians, with the final scores being computed as averages.

Figure 2

Mean scores of GPT-4 and Opus (1 denoting maximum accuracy) in correctly identifying the diagnosis (left) and in including the main diagnosis in the list of differential diagnoses (right).

Results

Opus achieved a higher mean accuracy (0.74) compared to GPT-4 (0.56) in determining the correct diagnosis, with the observed difference being statistically significant (p = 0.043). Nevertheless, both models demonstrated comparably high accuracy in incorporating the primary diagnosis within the differential diagnoses, with scores of 0.90 for GPT-4 and 0.88 for Opus (Figure 2). Additionally, both models (GPT-4 average score 1.79 ± 0.43, Opus 1.75 ± 0.50) performed well in providing accurate descriptions of different clinical images. In terms of image type, they performed best in interpreting images with physical findings (GPT-4 1.92 ± 0.23, Opus 1.83 ± 0.46), followed by radiographic images (GPT-4 1.80 ± 0.41, Opus 1.83 ± 0.36), and worst in pathological specimens (GPT-4 1.61 ± 0.58, Opus 1.57 ±0.58) (Figure 3). No statistical differences were found between the two models in their overall ability to describe images or within each image category.

Figure 3

Mean accuracy scores of GPT-4 and Opus (up to 2) in interpreting clinical images grouped according to image type.

Conclusion

The two models demonstrated comparable accuracy in handling complex infectious disease scenarios that integrated both texts and images, suggesting potential utility in enhancing clinical support.

Disclosures

All Authors: No reported disclosures
P-2231. The Impact of Cell-free DNA Sequencing in the Evaluation and Management of Infections
Authors: Marshall Maurice , Monday Lea M , Laporte Matthew , Fairfax Marilynn , Kennedy Timothy R , Abdel-Haq Nahed M , Salimnia Hossein , Dhar Sorabh
Published: January 2025

Background

Cell-free DNA Sequencing is a novel diagnostic test that utilizes next generation sequencing to detect pathogens directly from plasma. Microbial cell-free DNA (mcfDNA) can be detected for a large number of pathogens with high analytic sensitivity and specificity; however, testing may be cost prohibitive and the direct impact on clinical care decisions is unclear.

Methods

A retrospective review was performed at a large inner-city tertiary care medical center from 9/2021 to 3/2024 to assess the results of mcfDNA sequencing (using the Karius Test®) on committee approved patients for whom infection was suspected, and without a definitive diagnosis on traditional microbiologic testing or in patients not improving on current antimicrobial therapy. Clinical, microbiologic, and outcome data were collected, and the impact of a positive or negative test on clinical care decisions was abstracted. Test results were defined as impactful if they led to change in the antimicrobials (e.g. additional agents, dosing adjustment, or discontinuation of antimicrobials).

Results

Testing was completed on 25 patients, ranging from 5 months to 63 years (mean age 17 years), 16 (64%) female, 12 (48%) immunocompromised. The average result reporting time was 2.6 days. 23 (92%) patients received antibiotics prior to testing with an average duration of 30.8 days. A total of 13 (52%) of tests were positive by mcfDNA (with a mean of 1.6 organisms (SD=0.65) detected), and 7 (53.8%) polymicrobial results. The positive vs negative did not vary by suspected site, though sample size was small (Fig1). A total of 15 (60%) patients were positive by traditional microbiology tests with an organism correlation of 5 (20%). The mcfDNA results were impactful in 9 (36%) of the patients. A positive test was more likely to be impactful than a negative test (p=0.01). Ninety-day mortality was noted in 10 (40%) of patients and the average duration of hospitalization was 75.5 days – with no difference among patients with a positive mcfDNA (Table 1).

Conclusion

A positive mcfDNA sequencing result was noted to be clinically impactful in 36% of cases. Our data suggests that testing would be most beneficial for patients that lack a definitive infectious diagnosis or those not responding to appropriate therapy.

Disclosures

All Authors: No reported disclosures
P-2236. Performance Characteristics of Procalcitonin in the Inpatient Setting
Authors: Park Albert , Nakasone Trisha S , Kaushal Amit , Renault Cybele
Published: January 2025

Background

Procalcitonin (PCT) is a marker used in clinical decision-making for suspected bacterial infections. While its efficacy in guiding antibiotic de-escalation when used as a trend is well-established, its use as a stand-alone value is prevalent in both ICU and non-ICU settings despite the absence of evidence-based guidelines. Our study evaluates the performance of PCT as individual values and aims to discern organisms associated with true positive or false negative PCT values.Figure 1.Performance characteristics of PCT by site of infection

Methods

We performed a retrospective cohort study of patients at the Palo Alto Veterans Affairs Medical Center who underwent PCT testing from 1/1/2020 to 9/28/2023. We identified cultures drawn within 3 days of each PCT value to characterize the diagnostic performance of individual PCT values. Subsequently, we excluded organisms identified within 1 week of each other and performed one-sample z-tests for proportions to identify organisms associated with true positive (TP) or false negative PCT values based on site of infection.Figure 2.Microorganisms associated with true positive vs. false negative PCT from all culture sites

Results

3204 patients underwent PCT testing during the study period and 4027 cultures were drawn. Blood culture PCT sensitivity was 0.618, specificity 0.580, positive predictive value (PPV) 0.204, and negative predictive value (NPV) 0.896 (Figure 1). Respiratory culture PCT sensitivity was 0.555, specificity 0.594, PPV 0.620, and NPV 0.529. 2495 organisms separated by at least 1 week from each other were identified by culture. Enterobacterales (TP rate 82.2%), Staphylococcus aureus (TP rate 81.6%), Streptococcus pneumoniae (TP rate 84.6%), and non-pneumococcal Strep. (TP rate 74.1%) were strongly associated with positive PCT values in blood cultures (Figures 2 and 3). Enterobacterales (TP rate 63.1%) and Strep. pneumoniae (TP rate 74.2%) were strongly associated with positive PCT values in respiratory cultures.Figure 3.Microorganisms associated with true positive vs. false negative PCT by site of infection

Conclusion

While the NPV of individual PCT values is 89.6% for blood cultures, individual PCT values otherwise have limited diagnostic accuracy for active infections. Certain organisms show stronger associations with positive PCT values. Further investigation may offer insights into specific bacterial characteristics that drive PCT response in infected patients. However, in most cases, culture-identified organisms do not reliably correlate with positive PCT values.

Disclosures

All Authors: No reported disclosures
P-2239. RNA Signatures for Diagnosing or Predicting Febrile Illness: A Descriptive Analysis
Authors: Kozlowski Hannah N , Womersley Rebecca , Brophy-Williams Sam , Di Chiara Costanza , Huang Ryan S , Wong Nikki , Lee Katie , Peresin Joelle , Morris Shaun
Published: January 2025

Background

Fever is a common sign of illness; it may self-resolve or be present in serious illnesses requiring hospitalization. Investigating the cause of fever can be extremely resource intensive requiring multiple diagnostic tests and healthcare providers thereby delaying time to diagnosis. RNA molecules present in the blood can be easily detected and reflect a patient’s disease state, making them ideal biomarkers.

Our objective was to identify RNA common to signatures that diagnose and predict the outcome of febrile illnesses. Our secondary objectives were to assess whether signatures are being validated and translated.

Methods

We conducted a scoping review of published research articles, including preprints, from EMBASE and Medline that measured blood RNA in patients with febrile illness. Here we are analyzing a articles that used array or RNA-seq to generate original signatures.

Results

We identified 248 original blood RNA signatures for the diagnosis or prognosis of febrile illness. 154 were diagnostic, 56 prognostic, 15 diagnostic/prognostic and 23 exploratory. The most common illnesses studied were sepsis (n=83), viral infections (n=74) and tuberculosis (n=38). From all sepsis signatures there were 214 unique RNA and 74 RNA present in multiple signatures. The most common RNA, C3AR1 (complement receptor) and MPO (myeloperoxidase), appeared in 5 signatures. For viral infections there were 54 signatures, and IFI27 (interferon) appeared in 8 signatures. For tuberculosis there were 26 signatures, and the most common RNA were BATF2 (transcription factor) and FCGR1B (Fc receptor) each appearing in 4 signatures.

158/248 signatures were validated. Clinical sensitivity and specificity in validation groups were 54-100% and 79-97%, respectively. 9/248 studies claimed that they had filed or were filing for a patent.

Conclusion

Blood RNA molecules can be used for the diagnosis and prognosis of febrile illnesses. Currently, < 65% of RNA signatures are validated and < 5% of signatures are commercialized. In conducting this analysis, we encountered a lack of standardization in methods reporting. Further work to improve transparency and encourage validation is needed so RNA signatures can be adapted into simple, molecular diagnostic tests and translated for patient use.

Disclosures

Shaun Morris, MD, MPH, DTM&H, FRCPC, FAAP, GSK Canada: Advisor/Consultant|GSK Canada: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi Canada: Advisor/Consultant|Sanofi Canada: Honoraria
P-2257. Pseudomonas aeruginosa and other Bacterial Infections After Lung Transplant: Risk Factors, Airway Stenosis and other Clinical Outcomes
Authors: Hernandez Acosta Ruben Alfonso , Gupta Simran , Chamberlin Elene , Woehl Ella , Connolly Erin M , O’Neill Audra , Coppolino Antonio , Sharma Nirmal S , Baden Lindsey R , Woolley Ann E
Published: January 2025

Background

Pseudomonas aeruginosa (PsA) and other bacterial infections after lung transplant can lead to worse patient outcomes. The aim of this study was to investigate whether isolation of microbial pathogens post-lung transplantation increased the risk of airway stenosis requiring bronchoscopic interventions.

Table 1Table 1.Demographic, donor/recipient characteristics, peri-operative/post-operative characteristics and outcomes.

Methods

A single-center retrospective study of lung transplant recipients (LTR) between January 2017 and October 2023 was performed. Our center performs routine surveillance bronchoscopies at 1, 3, 6 and 12 months. Donor/recipient characteristics, microbiologic data, bronchoscopy findings and interventions, and 1-year outcomes were analyzed.

Results

In this 6.8-year study period, 327 subjects underwent lung transplant with survival greater than 30 days. The most common indication for lung transplant was restrictive lung disease. 64 (20%) had PsA infections, 77 (23%) had non-PsA bacterial infections (infect), and 186 (57%) did not have a bacterial infection within 6-months post-transplant. Recipient and donor characteristics were similar among the cohorts. A greater proportion of the PsA and infect cohorts required dialysis and mechanical ventilation and/or ECMO for >48 hours and had a longer index hospitalization than the uninfected cohort [Table 1]. A greater proportion of the PsA and infect cohorts developed airway stenosis requiring bronchial intervention (22% vs 17% vs 2%, p=< 0.001). The median time to first infection post-transplant occurred prior to the development of stenosis (72 vs 112 days; 52 vs 110 days). 44% of LTR with PsA growth had fluoroquinolone resistance on the initial culture. Rates of rejection and 1-year survival were not statistically different among the cohorts.

Conclusion

PsA and other bacterial infections within the first 6-months post lung transplantation led to a higher incidence of airway stenosis requiring bronchial intervention but was not associated with increased mortality or rejection at 1-year. The impact of treating bacterial colonization and other strategies to minimize post-transplant bacterial infections and decreasing the occurrence and time to airway stenosis needs further study.

Disclosures

All Authors: No reported disclosures
P-2258. Characterizing real world infection risk in multiple myeloma patients receiving teclistamab
Authors: Guare Emma , Song Chen , Inoue Yoshitaka , Sandhu Manpreet , Sivik Jeffrey , Rakszawski Kevin , Naik Seema , Minagawa Kentaro , Mineishi Shin , Paules Catharine I
Published: January 2025

Background

Teclistamab is an anti-B-cell maturation antigen (BCMA) bispecific antibody used in relapsed, refractory multiple myeloma (MM) that induces durable responses but is associated with high rates of infectious complications. Real world data are needed to further characterize infection risk in patients receiving teclistamab.Table 1.Patient characteristics between infected and non-infected patients

Methods

A retrospective single-center study of teclistamab treated patients with relapsed, refractory MM from 1/1/2023 to 11/20/2023. Patients received teclistamab according to a step-up dosing regimen, with Day 0 defined as first step-up dose. The primary objective was to report the incidence, type, and timing of infection. Differences in demographics and clinical characteristics were described between infected and non-infected patients.Table 2.Patient outcomes on teclistamab between infected and non-infected patients

Results

19 patients received teclistamab; median age 72 years, 73.7% white, and 26.3% with Karnofsky performance status ≥ 80 (Table 1). 11 (57.9%) patients developed infections and 5 had more than one infection. There were 3 bacteremias, 6 other bacterial infections (urinary tract infection, pneumonia, cholangitis, osteomyelitis, sinusitis), 6 respiratory viral infections, and 2 cytomegalovirus (CMV) reactivations. There were no documented infections with herpes simplex virus, varicella zoster virus, Pneumocystis jirovecii, or fungal pathogens. The median time to any infection was 17 days (range 2, 266), with a median of 20 days (range 2, 123) to bacterial infection and 31 days (range 3, 266) to viral infection (Figure 1). Patient characteristics and antimicrobial prophylaxis strategies were largely similar between infected and non-infected patients (Table 1). There was a nonsignificant trend toward increased immune effector cell-associated neurotoxicity syndrome (ICANS) and increased use of steroids in the infected group. 10 patients in the infected group discontinued teclistamab (p=0.013) and 3 died (p=0.108, Table 2).Figure 1.Cumulative incidence of any infection (A), bacterial infection (B), and viral infection (C).

Conclusion

The incidence of infection was high amongst patients receiving teclistamab and increased with time. Individuals with infections were more likely to discontinue teclistamab. Further data are needed to inform guidance regarding infection prevention strategies and criteria for teclistamab interruption or discontinuation in this MM population with few other treatment options.

Disclosures

Kevin Rakszawski, MD, AstraZeneca: Speakers Bureau|Pfizer: Speakers Bureau Seema Naik, MD, ADC Therapeutics: Advisor/Consultant|ADC Therapeutics: Board Member|ADC Therapeutics: Honoraria|Janssen: Advisor/Consultant|Janssen: Board Member|Janssen: Honoraria|Onclive: Honoraria|Onclive: Speaker
P-2276. Shifting trends over time in patients admitted with presumed or confirmed Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection from 2006 to 2023 in Singapore
Authors: Koh Matthew C Y , Ngiam Jinghao Nicholas , Tambyah Paul , Lum Lionel H W
Published: January 2025

Background

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection associated with significant morbidity and mortality in immunocompromised hosts. PJP has emerged as a significant pathogen affecting non-HIV infected hosts, with wider use of novel immunosuppressive therapies. We sought to describe changing trends in the clinical profile and outcomes of patients without underlying HIV diagnosed with PJP.

Clinical characteristics of patients with pneumocystis pneumonia without underlying HIV

Clinical characteristics of patients with pneumocystis pneumonia without underlying HIV

Methods

A total of 93 consecutive patients without HIV, with presumed or confirmed PJP, admitted to a tertiary hospital in Singapore were studied from 2006-2023. The cohort was divided into the first 44 patients from 2006-2014, and the second 49 patients from 2015-2023. Data on each patient’s clinical background, presenting symptoms, laboratory data as well as clinical outcomes such as need for intensive care, mechanical ventilation or mortality were tabulated.

Results

Over the years, there was no significant differences in the age or sex of patients with PJP. However, there was a decrease in proportion of haematological malignancy as a predisposing condition for PJP (38.6% vs 14.3%), but an increase in the proportion of patients with autoimmune/inflammatory conditions presenting with PJP (13.6% vs 26.5%). A smaller proportion of patients presented without PJP prophylaxis in more recent years (100.0% vs 81.6%, p=0.030), and shortness of breath was a less common symptom (90.9% vs 63.3%, p=0.002). A greater proportion of patients were diagnosed using PJP PCR. Overall mortality (36.4% vs 26.5%), as well as the need for mechanical ventilation (31.8% vs 34.7%) and intensive care (50.0% vs 53.1%) did not differ between the groups.

Conclusion

In this single centre retrospective study, there have been significant changes over almost two decades in the clinical profile of patients without underlying HIV who had PJP infection. A greater proportion of patients had autoimmune and inflammatory conditions, while the proportion of those with haematological malignancy decreased. This may be due to the implementation of standardised protocols for PJP prophylaxis. More cases were detected using PCR, which appears to be a helpful adjunct to microscopic examination. Morbidity and mortality from PJP in such non-HIV immunocompromised hosts however remains high and has not declined over the years.

Disclosures

Paul Tambyah, MBBS (S'pore), Diplomate, American Board of Internal Medicine and Infectious Diseases, Moderna: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support
P-2277. Impacts of Ongoing Quinolone Prophylaxis Following Quinolone-Resistant Bacteremia in Neutropenic Patients
Authors: Acevedo Sarah , Park Stacy
Published: January 2025

Background

Guidelines that suggest fluoroquinolone (FQ) prophylaxis for intermediate to high-risk hematologic malignancy patients are based primarily on evidence of reduction in bloodstream infections (BSIs) in historic studies, despite no demonstrated reduction in other outcomes such as mortality, septic shock, or ICU admissions. In the era of widespread FQ use for prophylaxis and increasing antimicrobial resistance, ongoing re-evaluation of the benefit is needed. Patients with BSI due to FQ-resistant gram-negative organisms may have particularly reduced benefit from ongoing FQ prophylaxis, however data on this topic is limited. We evaluated characteristics of neutropenic patients with BSI in an attempt to better inform the risk/benefit balance in this population.

Figure 1.

Numerical breakdown of bacteremia episodes

Methods

We extracted episodes of gram-negative BSI during a neutropenic episode lasting at least 7 days in adult inpatients with hematologic malignancy and/or stem cell transplant (study period 11/1/2020-11/1/2023). For each BSI episode we collected data on treatment (agent, duration, line removal), FQ susceptibility, underlying disease, neutropenia, and FQ exposure within 90 days. For episodes with an opportunity to resume prophylaxis following treatment of bacteremia (based on persistent neutropenia or recurrent neutropenia with 90 days), we determined rates of recurrent BSI within 90 days, stratified by FQ resistance and decision to resume FQ prophylaxis.

Results

There were 82 BSI episodes (69 first episodes, 13 recurrent) among 62 patients. FQ resistance was common in first episodes (34/69, 49%) and median prior FQ exposure within 90 days was 16 days. 43 episodes had an opportunity to resume FQ prophylaxis and 19/43 (44%) had FQ resistance. FQ prophylaxis was resumed in 16/19 (84%) with FQ resistance and 21/24 (88%) without, with rates of recurrent bacteremia within 90 days of 44% and 29% respectively. There were no episodes of recurrent bacteremia when FQ prophylaxis was not resumed (0/6).Table 1.Characteristics of bacteremia episodes with an opportunity to resume fluoroquinolone prophylaxis following treatment

Conclusion

Among bacteremia episodes with eligibility for FQ prophylaxis following treatment, recurrent bacteremia was common, particularly when FQ resistance was present. FQ prophylaxis may have little or no benefit in this setting, however larger studies and controlled data are needed.

Disclosures

All Authors: No reported disclosures
P-2278. CMV Viremia and Disease in Pediatric Liver Transplant Patients: a Multi-national Systematic Review and Meta-analysis
Authors: Shieb Mohamad , Stern Eric J , Hasanain Rand
Published: January 2025

Background

Cytomegalovirus (CMV) viremia (Defined as a single detectable CMV RNA PCR) and disease (defined as CMV viremia with compatible systemic and/or localized signs and symptoms) remain a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient. This systemic review aims at pooling data from the leading pediatric transplant institutions globally to identify the overall incidence of and risk factors associated with CMV viremia and/or disease in pediatric liver transplant recipients.

PRISMA flow diagram

Methods

A systemic review of Pubmed and OVID databases was conducted since the inception to 01 April 2024. 24 articles were included from the USA, UK, South Africa, India, Japan, Finland, Canada, Turkey, Mexico, Thailand, Greece, Israel and Australia. A total of 1964 liver transplants were included. Median age was 50 months with 47.8% males. Data related to demographics, incidence, donor and recipient CMV serological classification (Donor (D) and Recipient (R)) and risk factors for CMV viremia/disease were extracted from the articles and subsequently analysed. This review was registered in Prospero: CRD42023477476

Results

The Incidence of CMV viremia and disease in pediatric liver transplant patients in this review were 34% and 8.4% respectively, with statistically significant higher risk in the CMV D+/R+ category compared to other D/R serologic groups (P value < 0.05). , Additional risk factors identified for CMV viremia/disease included younger age, biliary atresia, high steroid doses, and rejection attacks.

Conclusion

This meta-analysis highlights that CMV viremia and disease post-liver transplantation are significant health concerns in pediatric populations. Identifying high risk populations for targeted CMV monitoring and potentially preemptive therapy to mitigate CMV-associated morbidity and mortality is a critical cornerstone of pediatric transplant medicine. Further studies are warranted to explore additional risk factors and to refine prevention and treatment strategies for CMV in pediatric transplant recipients.

Disclosures

All Authors: No reported disclosures
P-2299. Febrile neutropenia in cancer: a retrospective analysis in a dominican tertiary hospital
Authors: Reyes Yeison , Chaddy Báez Lia Michelle , Disla-Pineda Karla Marie , Calcano Ruben , Guzman-Ricardo Francisco , Ledesma Jose
Published: January 2025

Background

Febrile neutropenia (FN) poses a significant threat to cancer patients, often leading to severe infections. This study aims to characterize the epidemiology and sources of infection among hospitalized cancer patients experiencing FN at Hospital General de la Plaza De la Salud. By elucidating these factors, we strive to enhance patient care and outcome within our context.

Source: Statistical registry of the authors.

Methods

We conducted a retrospective study at a 289-beds in a tertiary care center in the Dominican Republic from March 2021 to March 2024, assessing 258 hospitalized patients with severe neutropenia. 42 cancer patients met the inclusion criteria (absolute neutrophil count less than 500 cells/µL and fever greater than 38.3°C) and data was collected reviewing the eCharts.

Source: Statistical registry of the authors.

Results

24 patients were male (57.1%), with a median age of 44 (IQR=27). 34 (80.9%) patients had hematologic malignancy, with acute myeloid leukemia being the most common (n=19; 45.2%), followed by non-Hodgkin lymphoma (n=7; 16.7%). Cause of fever was identified for 28 patients, which included bacteremia (13/28; 30.9%), respiratory tract infection (7/28; 16.7%), skin and soft tissue infection (5/28; 11.9%) and others (3/28; 10.7%). An etiological agent was documented in 20 cases, of which the most common was bacterial (15/20;75%); Pseudomonas aeruginosa (6/15; 40%), Escherichia coli (5/15; 33.3%), and Klebsiella pneumoniae (2/15; 20%), 4/20 (20%) were viral; 3/4 due to SARS-COV2 and 1/4 due to dengue, and 1/20 (5%) had Candida albicans. 14 (33.3%) patients had fever of unknown origin. 24/42 patients (68%) had a MASCC score < 21. Mortality rate was 30.9% (n=13), of which 12 (92%) had a MASCC score < 21 (p=0.02).

p=0.33.

Source: Statistical registry of the authors.

Conclusion

This study emphasizes how infectious complications greatly impact cancer patients experiencing febrile neutropenia, especially those with hematologic malignancies. Bacterial infections, notably Pseudomonas aeruginosa and Escherichia coli, are prevalent, highlighting the urgency of precise diagnostic methods for tailored antimicrobial treatment. The link between low MASCC scores and higher mortality rates focuses the importance of this risk assessment tool in guiding clinical decisions. These findings stress the necessity for improved multidisciplinary strategies to enhance the outlook for this vulnerable patient group.

MASCC risk vs outcome

p=0.02

Source: Statistical registry of the authors.

Disclosures

All Authors: No reported disclosures
P-2300. Invasive Pulmonary Aspergillosis-Mimicking Pseudomonas aeruginosa Pneumonia in Immunocompromised Patients
Authors: Yoon Choseok , Chang Euijin , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Kim Sung-Han
Published: January 2025

Background

Pseudomonas aeruginosa (PA) pneumonia is occasionally misdiagnosed as invasive pulmonary aspergillosis (IPA) in immunocompromised patients, especially transplant recipients or those with hematologic malignancy who have risk factors for IPA. However, there are limited data on this area. We thus investigated the clinical features and CT findings of PA pneumonia in immunocompromised patients.

Methods

All immunocompromised patients who were diagnosed as PA pneumonia was retrospectively reviewed in a tertiary hospital between 2017 and 2023. PA pneumonia was classified as follows; “confirmed”: positive culture from sterile tissues (blood, tissue, etc.) with radiologic compatible findings with pneumonia, “probable”: i) abnormalities on chest X-ray, ii) culture growth from non-sterile sources such as sputum or bronchoalveolar lavage fluid, iii) improvement with the use of anti-pseudomonal antibiotics without the use of antifungal agents, and “possible”: cases that do not meet the above criteria but cannot rule out PA pneumonia.

Results

Of 16 immunocompromised with PA pneumonia, 13 (81%) were male, and 9 (56%) were transplant recipients. Of these 16 patients, 9 (56%) were classified as “confirmed”, 5 (31%) “probable”, and the remaining 2 (13%) “possible”. 7 (44%) patients with PA pneumonia had concurrent IPA, with 1 proven IPA and 6 probable IPA. The remaining 9 patients with PA pneumonia alone revealed macronodules (n=5), mass-like consolidation (n=6), cavitary lesions (n=6), and halo sign (n=4) in initial CT findings. Of the 16 patients with PA pneumonia, 4 (25%) received inappropriate antifungal therapy.

Conclusion

About half of immunocompromised patients with PA pneumonia had concurrent IPA, but about one quarter of immunocompromised patients with PA pneumonia received inappropriate antifungal therapy.

Disclosures

All Authors: No reported disclosures
P-2314. Assessing Hazard Ratio of Recurrent Spontaneous Bacterial Peritonitis: Impact of Antibiotic Prophylaxis in Cirrhotic Patients
Authors: Nguyen Trong-Tuong , Arab Niki , Kim Brian , Jeng Arthur
Published: January 2025

Background

Spontaneous bacterial peritonitis (SBP) is a severe infection of the ascitic fluid in individuals with advanced liver disease and ascites. The American Association for the Study of Liver Diseases recommends antibiotic (abx) prophylaxis (ppx) for patients with a history of SBP, low ascitic fluid protein (< 1.5 g/dL), or advanced cirrhosis with ascites. However, prophylactic antibiotics cause collateral damage and their efficacy in reducing SBP recurrence remains uncertain. This study assesses the recurrence rates between groups receiving prophylaxis and those without.

Methods

Single centered, retrospective cohort study aimed to estimate the hazard ratio (HR) for recurrent SBP in patients with and without SBP ppx. Patients meeting criteria of cirrhosis with documented ascites and polymorphonuclear leukocyte count ≥ 250 cells/µL were randomly selected between 2017 to 2023. The primary outcome was time to recurrent SBP. Cox proportional hazard models were used to estimate the HR and 95% confidence intervals (CIs).

Results

38 patients were included, 4 patients received SBP ppx. The HR for recurrent SBP was not statistically significant [0.765 (95% CI -1.58, 1.04)] between use of SBP ppx and those with no ppx abx. This analysis was controlled for age, gender, alcohol use, cancer, diabetes, chronic kidney disease, chronic lung disease, autoimmune disease, and HIV status. Incidentally we found that, of the 4 patients who received prophylaxis, 2 developed extended spectrum beta lactamase (ESBL) producing gram negative infections in either ascitic or blood cultures.

Conclusion

Our analysis did not demonstrate a statistically significant difference in the hazard of recurrent SBP between patients with versus without ppx. SBP ppx was found to have potential risk of recurrent SBP with more resistant ESBL-producing pathogens for those on SBP ppx. Additional study may be warranted to further elaborate the benefit vs risk of SBP ppx in terms of development of resistance.

Disclosures

All Authors: No reported disclosures
P-2326. The Under-recognized Burden of Lassa Virus Infection in Liberia
Authors: Nimely Catherine , Kerkula Emmanuel , Krajewski Taylor , Colt McKenzie , Flomo Alfred , Fofana Amara , Kerkula Stanley , Remont Thomas , Watts Rosie , Tozay Sam , Mollan Katie R , Zivich Paul , Ricks Minnie , Wohl David A , Fischer William A , Sibley Jefferson
Published: January 2025

Background

Lassa virus (LASV) is a persistent and lethal threat in endemic regions of West Africa. While severe disease due to Lassa fever (LF) is responsible for 5000-10,000 deaths annually, there is evidence of a wide spectrum of clinical manifestation of LASV infection.

Methods

The Coalition for Epidemic Initiative (CEPI) sponsored ENABLE study is a prospective, observational, cohort study of the prevalence and incidence of LASV infection and LF in five West African countries: Nigeria, Liberia, Sierra Leone, Guinea, and Benin. LASV seroprevalence was determined by LASV nucleoprotein (NP) IgG at entry (ReLASV NP IgG ELISA). Participants were assessed every 2 weeks in-person for fever with and without LF symptoms. Febrile events triggered LASV RT-PCR (RealStar Lassa Virus RT-PCR Altona 2.0). To assess for subclinical LASV infection, serum was collected every 6 months for 2 years from a subset (Infection Cohort) for LASV NP IgG.

Results

In Liberia, 5,005 were enrolled between April 2021 and December 2023; 25 withdrew before data collection. Of the remaining 4,980 participants, 1,018 were in the Infection Cohort and 591 of these provided samples at all 5 time points. At entry, 2,259 (45%) were LASV NP IgG positive. Entry LASV NP IgG seropositivity increased with age with the lowest prevalence among those 2-5 years (101 of 510, 20%, CI: 17-24%) rising to a peak among participants 30-39 years (322 of 564, 57%, CI: 53-61%). Of the 591 with serological results at all 5 timepoints, 314 (53%) were LASV NP IgG negative at study entry and 68 (22%) had at least a single change in serostatus from seronegative to seropositive. Over 24-months, 1,176 febrile events in 818 participants were identified and of these 10 (1%) had LASV RNA detected.

Conclusion

In this 24-month longitudinal study of individuals in a LASV hyperendemic area of West Africa, close to half were LASV seropositive at enrollment, and across two years of follow-up, 1 in 5 participants who were LASV seronegative at entry had observed seroconversion. However, only a small number of LF cases (n=14) were identified through symptom-driven testing dependent on fever. These findings indicate that in this region of Liberia LASV infection is common, increases during the first decades of life, but is rarely clinically detected.

Disclosures

Katie R. Mollan, MS, Gilead Sciences: Grant/Research Support|Ridgeback Biotherapeutics: Grant/Research Support
P-43. A Single Composite Peptide Vaccine Comprising Conserved Influenza Epitopes Formulated with ALFQ Adjuvant Induced Broadly Reactive Antibodies to Human, Avian, and Swine Influenza Viruses
Authors: Rikhi Nimisha , Sei Clara J , Rao Mangala , Kroscher Kellie , Matyas Gary , Schuman Richard F , Muema Kevin , Lange Camille , Assiaw-Dufu Aba , Alving Carl R , Fischer Gerald W
Published: January 2025

Background

Reassortant influenza strains containing genes from human, avian, and/or swine origin, have led to major outbreaks, such as the 2009 swine flu pandemic. The ongoing global spread of highly pathogenic avian influenza (HPAI) A/H5N1 virus among poultry highlights the risk of zoonotic transmission leading to pandemics. A universal influenza vaccine that generates broadly neutralizing antibodies against influenza viruses is crucial for preventing future pandemics. Previous studies with our unconjugated composite peptide vaccine (two-peptide combination), which targets multiple highly conserved epitopes on influenza virus, generated broadly reactive antibodies to human and avian strains, including HPAI A/H5N1 viruses. A single peptide vaccine approach offers formulation and scale-up advantages. Here, we demonstrate that a novel, unconjugated, single composite peptide vaccine comprising highly conserved epitopes of hemagglutinin (HA), neuraminidase (NA), and matrix (M1/M2/M2e), and a universal T cell epitope, formulated with the highly potent adjuvant Army Liposomal Formulation with QS21 (ALFQ), induced broadly reactive antibodies to human, avian, and swine influenza strains.

Methods

ICR mice were immunized intramuscularly on days 0, 21, and 35 with 2μg of composite influenza peptide vaccine LHNVD-110, formulated with ALFQ adjuvant. Isotype-specific IgG titers to peptides and influenza A (H1N1pdm09, H3N2, HPAI H5N1) and B (Victoria, Yamagata) viruses were analyzed by ELISA. Neutralizing titers were determined using the microneutralization assay and inhibition of HA using the HAI assay.

Results

Robust serum IgG1 antibodies to human, avian, and swine influenza A and B viruses were induced. Post-immunization serum demonstrated neutralization and HA inhibition of Group 1 and 2 influenza viruses.

Conclusion

An unconjugated single composite peptide vaccine comprising highly conserved HA, NA, and matrix epitopes, formulated with ALFQ adjuvant, generated broadly reactive antibodies to human, avian, and swine influenza strains and neutralized seasonal and pandemic strains. This single composite peptide vaccine provides a cost-effective, and easily scalable strategy towards a universal influenza vaccine to combat future pandemics.

Disclosures

All Authors: No reported disclosures