bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2110. Evaluating Different Screening Methods to Assess the Prevalence of Gut Colonization with Multidrug-Resistant Gram-Negative Bacilli in Hospitalized Patients
Authors: Tenner Rebecca A , Riquelme Maria Paz , Acevedo Johanna , Maureira Quezada Lea Paz , Valentina Gonzalez Soto Maite Loreto , Martínez Jose R W , Diaz Lorena , Peters Anne S , Araos Rafael , Munita Jose M
Published: January 2025

Background

Accurate estimates of gut colonization with drug-resistant gram-negative bacilli (GNB) are key to combat antimicrobial resistance. Data on best practices to assess colonization is scarce, limiting the comparability and feasibility of screening efforts. Building upon ongoing projects studying gut colonization with carbapenem-resistant (CR), carbapenemase-producing (CP-CR) and extended-spectrum beta-lactamase-producing (ESBL) GNB in Chile, we compared 3 different screening strategies and assessed the impact of time between swab collection to plating.

Prevalence of Gut Colonization with Multidrug-Resistant Gram-Negative Bacilli Detected with Different Screening Methods

Methods

Rectal swabs were collected for a gut colonization point-prevalence study in 3 Chilean hospitals (n=127, 149, 150). All swabs were plated within 2h of collection onto separate MacConkey agars with CAZ 2µg/mL and CIP 2µg/mL (CAZ|CIP). In hospital A samples were also plated on MacConkey + ceftriaxone 2µg/mL (CAZ|CIP|CRO). In hospital B swabs were also plated onto CHROMagar ESBLTM (CAZ|CIP|CHR). Swabs from Hospital C were plated on CAZ|CIP within 2h(immediate) and were then re-streaked after 48h at room temperature (delayed plating). After 24h of incubation at 37°C, all isolated morphotypes were characterized. Prevalence of gut colonization between CAZ|CIP, CAZ|CIP|CRO and CAZ|CIP|CHR were compared, as were plating times for hospital C.

Results

Results are summarized in Table 1. Prevalence of gut colonization in hospital A using CAZ|CIP vs. CAZ|CIP|CRO was similar for MDR-GNB (24% vs 28%), CR-GNB (13% vs 14%), and CP-CR-GNB (3% vs 4%). The addition of CRO detected a higher prevalence of ESBL-GNB compared to CAZ|CIP alone (50% vs 41%; p=0.04). In hospital B, CAZ|CIP|CHR detected a higher prevalence of colonization with CR-GNB (21% vs 16%, p=0.016) and ESBL-GNB (44% vs 36%, p < 0.001), but similar results for MDR-GNB and CP-CR-GNB as compared to CAZ|CIP. The prevalence of gut colonization did not vary between immediate vs. delayed plating (Hospital C).

Conclusion

The addition of a CRO or CHR agar increased the detection of gut colonization with ESBL-GNB compared to a CAZ|CIP protocol. CHR also provided a higher yield of CR-GNB. However, observed CP-CR-GNB prevalence was similar among all 3 conditions. Finally, a delayed plating strategy (48h) did not impact colonization detection as compared to immediate plating (2h).

Disclosures

Jose M. Munita, MD, MSD: Grant/Research Support|Pfizer: Grant/Research Support
P-2114. Pattern of Clinical Characteristics, Outcome and Comparison of Carbapenem Resistant and Carbapenem Sensitive Klebsiella Species Infections from a Tertiary Care Hospital, Karachi, Pakistan
Authors: Samar Rohama , Farooq Mohammad Kashif , Babar Zaheer Udin , Dodani Sunil
Published: January 2025

Background

The prevalence of carbapenem resistant (CR) Klebsiella species (KS) is greater than 60 % in South Asia with high morbidity and mortality. Data on clinical aspects of KS from Pakistan is scarce. We aimed to study clinical characteristics, outcome and risk factors for mortality among KS infection

Methods

A prospective study conducted from September 2022 to March 2023. All patients greater than 18 years with active KS infection were included. Age, gender, clinical features, Charlson co-morbidity index, source of infection, previous hospitalization, source control and appropriate empirical antibiotics received were noted. Outcome was documented as admitted, discharged or death at day 14.

CRKS and carbapenem sensitive (CSKS) were compared.Table 1:Demographics, Risk factors and outcome of CRKS and CSKS infection.

Results

Out of 217, 128 (58.9%) CRKS and 89 (41%) CSKS infection. The median age was 48 years, 39.6% female. Around 114 (52%) had previous hospitalization. Bacteremia 103(47.5) was most common. At day 14, all-cause mortality was 29%. CRKS infection was significantly associated with recent hospitalization, fever, altered mental status, ICU admission and mechanical ventilation.

Pneumonia was more common with CRKS (p=value 0.004). Among CRKS, 4 (3.2%) received appropriate empirical antibiotics and had poor bacterial clearance (p=0.048). A survival curve shows significant high mortality in CRKS over 14 days. On multivariate analysis patients with CRKS did not receive appropriate empirical antibiotics.Table 1:Demographics, Risk factors and outcome of CRKS and CSKS infection.

Conclusion

We found a very high proportion of CRKS infection with high morbidity and mortality. Patients with CRKS infection did not receive appropriate empirical antibiotics. Timely availability of antibiogram with good infection control practices are critical in preventing mortality and spread this highly pathogenic organism.

Disclosures

All Authors: No reported disclosures
P-2117. ETEST® Aztreonam-Avibactam (AZA) for Antimicrobial Susceptibility Testing of Enterobacterales: Performance Results From a Muticenter Study
Authors: Prudhomme Sarah , Bossy Louise , CSIKI-FEJER Edith , Hardy Dwight , Wootton Mandy , Yarbrough Melanie L , Pillon Edwige , Franceschi Christine
Published: January 2025

Background

AZA is a combination of Aztreonam, a monobactam not hydrolyzed by metallo-β-lactamases, and Avibactam, a novel non-β-lactam β-lactamase inhibitor with an extended spectrum that protects Aztreonam for hydrolysis by Ambler class A, class C, and some class D serine β-lactamases. Aztreonam-Avibactam is developed by Pfizer for the treatment of infections caused by Gram-negative bacteria, including metallo-β lactamase producers.

This study evaluated the performance of ETEST® AZA (bioMérieux Marcy-L’Etoile, France), a new gradient diffusion strip, for determining antimicrobial susceptibility of Enterobacterales compared to the CLSI/ISO-20776-2 broth microdilution reference method (BMD).

Methods

A population of 650 (clinical and challenge) Enterobacterales isolates (including 150 Escherichia coli; 118 Klebsiella pneumoniae; 48 Klebsiella oxytoca; 67 Enterobacter cloacae complex; 50 Citrobacter freundii complex; 30 Citrobacter koseri; 32 Klebsiella aerogenes; 30 Morganella morganii; 32 Proteus mirabilis; 30 Providencia stuartii ; 30 Proteus vulgaris ; 33 Serratia marcescens) were tested at 4 clinical trial sites, comparing ETEST® AZA and the BMD reference method.

Results were analyzed using preliminary EUCAST breakpoints (Enterobacterales: ≤ 8mg/L (S), > 8 mg/L (R)) and preliminary FDA breakpoints (Enterobacterales: ≤ 8mg/L (S), ≥ 16 mg/L (R)) provided by Pfizer. Results are presented as essential agreement (EA) and Bias for Worldwide registration and as essential (EA) and categorical (CA) agreements, Trend, very major (VME) and major (ME) error rates for US registration.

Results

Results are summarized in Table 1. ETEST® AZA performance for Enterobacterales met ISO acceptance criteria for EA (≥ 90%) and Bias ≤ ±30%, and FDA criteria for EA, CA (≥ 90%), ME (≤ 3%), VME (≤ 2%) and Trend ≤ ±30%.

Conclusion

Results of this multicenter trial support the accuracy of ETEST® AZA for determining MICs of Enterobacterales. As such, the ETEST® AZA test is considered to be equivalent to BMD.

Disclosures

Melanie L. Yarbrough, PhD, bioMerieux: Grant/Research Support|bioMerieux: Honoraria|Pattern Bioscience: Grant/Research Support|Shionogi: Advisor/Consultant
P-2138. The Significance of Low Titer Serum Cryptococcal Antigen Testing from 2017 to 2023
Authors: Wilson Jenna , Ribes Julie A , Irwin Mark , Myint Thein
Published: January 2025

Background

In the fall of 2016, a cluster of low positive serum cryptococcal antigen titers (SCrAg) ≤ 1:20 was traced back to a manufacturing defect. Subsequently, SCrAg ≤ 1:10 were reported with a disclaimer to correlate clinically at our institution. This study aimed to determine the performance of the assay since 2017, after the test improvement.

Comparison of Baseline Characteristics, Laboratory Findings and Outcome Among Three Groups

Methods

This was a retrospective study of patients with first time low titer SCrAg (≤1:20) tested at UK HealthCare from Jan 2017-Oct 2023. Patients were classified as true positives (TP), likely false positive (FP) and indeterminate based on repeat SCrAg, PCR or culture (CSF, Blood, respiratory, other), histology, correlating symptoms and/or detection of nodular infiltrates on CT, all extracted via chart review from the electronic medical record.

Number of Positive Serum Cryptococcal Antigen Samples Based on Titers​

Results

Of 3716 SCrAg performed during the study, 181 (4.9%) were positive. 69/180 (38%) positive samples were SCrAg ≤1:20. We excluded 32 TP tests due to prior higher SCrAg or prior history of cryptococcal meningitis and focused on the significance of newly identified low titer patients. 37 (0.9%) low titer SCrAg samples were seen in 27 patients. 19/27 patients (70.4%) were classified as TP, 2 (7%) FP, and 6 (22.2%) were classified as indeterminate (Table 1). Lumbar puncture (LP) was performed in 57.9% (11/19) of those classified as TP, and of those, 27.3% (3/11) had confirmed cryptococcal meningitis. Five of the nine patients that had histologic examination demonstrated organisms consistent with cryptococcosis. Antifungal therapy was administered in 100% (19/19) TP compared to 0% (0/2) FP (p < 0.01).

Conclusion

False positive low titer SCrAg are not frequent. When newly detected, these low titer positives are associated with additional corroborating evidence suggesting cryptococcosis. Patients with likely true positive SCrAg had respiratory and CNS symptoms and abnormal imaging more often than those with FP SCrAg. Low positive SCrAg should be extensively investigated for evidence of cryptococcal infection.

Disclosures

All Authors: No reported disclosures
P-2149. The Spectrum of Non-Valvular Cardiac Aspergillosis: What We Know So Far
Authors: Al khouri Zaid , Alqura’an Anood , Munshi Ruhul , Alam Mohammad , Malek Alexandre
Published: January 2025

Background

Invasive aspergillosis is a life-threatening infection that affects immunocompromised hosts. Cardiac involvement is rare, but it is associated with a high-mortality rate. Most cases reported infective endocarditis secondary to Aspergillus. However, there is limited data about non-valvular cardiac aspergillosis (NVCA). We performed a systematic review and added one case seen at our institution to highlight more on NVCA.

PRISMA Flow Diagram NVCA

Methods

Three reviewers searched PUBMED and EMBASE for all adult cases diagnosed with NVCA between 1950 and 2024 and assessed studies for eligibility (Fig 1). We added our case of 48 yo female with only congenital kyphoscoliosis diagnosed with isolated NVCA and was successfully treated with 6-month course of Voriconazole.

Results

We found 67 cases including ours. A 36% were females and 64% males with a mean age of 44.6 y (range, 18-79). 30% of patients did have underlying hematologic malignancy and in 15% there were no comorbidities identified. Diagnosis was made by cultures and histopathology either from the pericardial fluid, cardiac masses, or from the cardiac layers, and it was antemortem only in 39%. It was identified in the pericardium alone in 40%. In 51% of cases, the Aspergillus species were not identified, while the remaining were secondary to A. fumigatus. TTE was done in 60% and showed pericardial effusion or tamponade in 31.5%. A 67% had lung involvement and 52% had invasive aspergillosis. In terms of outcomes, 19% remained alive, and those Pts received anti-fungal therapy including voriconazole in 69% & amphotericin in 46% +/- intervention in 61.5%, while 75% expired including 38% who did not receive management, but the remaining did mostly use amphotericin in 30%.

Conclusion

NVCA is rare but highly fatal. Clinicians should keep a high-level of suspicion of this clinical entity, primarily in patients with liquid tumors and pericardial effusion. A combination of antifungal therapy, especially voriconazole along with minimally invasive or surgical intervention showed success in most cases.

Disclosures

All Authors: No reported disclosures
P-24. Toward the clinical development of ATI-1701, a genetically defined live attenuated tularemia vaccine
Authors: Nabors Gary S , Baran Arthur , Gelhaus Carl
Published: January 2025

Background

Tularemia is a life-threatening disease caused by the bacterium Francisella tularensis. While rare, the disease is notable for its wide host range, low infectious dose, high case fatality rate, and having been previously weaponized. Type A (F. t. tularensis) strains are found predominantly in North America and are generally more virulent than Type B (F. t. holarctica) strains. Both a killed whole cell (KWC) and a live attenuated (LA) vaccine were initially developed and underwent clinical testing in the pre-antibiotic era. While both types of vaccines generated strong antibody responses, later human challenge studies demonstrated that the KWC vaccine failed to protect against aerosol exposure. The LA strain designated LVS, which provided better protection against aerosol challenge but less robust protection against type A strains, was used until recently to immunize laboratory workers. Obstacles for approval of LVS include concerns regarding its undefined attenuation and potential for reversion to virulence. No acellular vaccines have proven to be as effective as LA vaccines.

Methods

ATI-1701 is a next-generation LA vaccine with a targeted, well-characterized mechanism of attenuation. ATI-1701 carries a clpB gene deletion, which is thought to inhibit its ability to escape from phagosomes, thereby limiting replication in host macrophages.

Results

Mice immunized ID with 10 CFU of ATI-1701 were fully protected from lethal challenge with the SCHU S4 strain. Rats vaccinated with one dose of ATI-1701 and challenged via aerosol exposure to 5,600 LD50 of virulent SCHU S4 survived infection up to one year post-challenge, whereas all unvaccinated rats died. Regardless of immunizing dose (103-109 CFU), spleens from vaccinated rats contained 103-105 CFU of ATI-1701 14 days after vaccination, and bacteria were cleared from the spleen prior to day 42. Immunization of cynomolgus macaques with a single dose of 105 CFU ATI-1701 protected 80-100% of animals challenged with up to 157,000 LD50 of SCHU S4 via aerosol exposure up to three months after vaccination. One year after vaccination approximately 30% of vaccinated macaques survived challenge whereas control animals died.

Conclusion

ATI-1701 is a promising tularemia vaccine candidate and is being positioned for a Phase 1 clinical trial.

Disclosures

All Authors: No reported disclosures
P-2169. Establishment of multiplex PCR method for nearly whole-genome sequencing of human parainfluenza/rubula virus 4 from a clinical sample
Authors: Sayama Yusuke , Sakamoto Masahiro , Okamoto Michiko , Saito Mayuko , Tamaki Raita , Saito-Obata Mariko , Joboco Christina Dahlia , Negosa Quicho Reynaldo Frederick , Lupisan Socorro P , Oshitani Hitoshi
Published: January 2025

Background

Human parainfluenza/rubula virus 4 (HPIV4) has two subtypes (4a/4b). HPIV4 infection is usually mild but can be severe in young children, older adults, and immunocompromised individuals. However, sequence information on HPIV4 is limited worldwide, including in tropical areas. Whole-genome sequencing is useful for the molecular epidemiological analysis of virus introduction and transmission routes. Thus, this study aimed to establish nearly whole-genome sequencing of HPIV4 subtypes using multiplex PCR (mPCR) methods and to identify genetic characterization in the Philippines.

Methods

We collected 29 (4a; n=17, 4b; n=12) HPIV4-positive samples from children (< 5 years old) with severe pneumonia at three hospitals (Leyte, Biliran, and Palawan) in the Philippines from 2012 to 2019. HPIV4 positive samples showed cycle threshold (Ct) values ranging from 21.1 to 36.9. An online pipeline tool (Primal Scheme) was used to design mPCR primer panels for HPIV4 subtype-specific viruses to cover the whole genome. For the sequencing experiment, viral RNA was purified from clinical samples and synthesized cDNA. cDNA was amplified using mPCR with each primer panel. The PCR amplicon was library preparation with a tag for the Illumina sequencing platform. Data of whole-genome sequencing was obtained using a CLC genomic workbench.

Results

All of the 29 HPIV4-positive samples were amplified by mPCR for whole-genome sequencing. The whole-genome sequencing results for HPIV4a showed that the length of consensus sequences generated at a coverage depth of 30X ranged from 85% to 99%. The sample with the lowest coverage (85%) had a Ct value 28.9. The results for HPIV4b showed that at a coverage depth of 30X, the length of consensus sequences ranged from 97% to 99%. The Ct values of the samples that showed 97% coverage were 22.6 and 30.4. Although some HPIV4 strains detected in the Philippines belonged to the same clade, others were in different clades. These clades included strains detected in various areas, such as Asia and North America.

Conclusion

This study established that the HPIV4 subtype-specific primer panels allow users to obtain the whole genome of HPIV4 directly from clinical samples. This method provides a universal, rapid, and effective tool for genomics surveillance.

Disclosures

All Authors: No reported disclosures
P-2186. Implementing Updated Hepatitis B Virus Screening Guidelines in an Underserved Resident Clinic
Authors: White Cole J , Weis John C , Barlow Mariah P
Published: January 2025

Background

An estimated 580,000 to 2.4 million Americans are living with hepatitis B virus (HBV) infection putting them at increased risk of cirrhosis, hepatocellular carcinoma, and death. Given these adverse outcomes, the Centers for Disease Control and Prevention recommended universal hepatitis B screening with a triple panel for all adults aged 18 and older starting in 2023. The purpose of our quality improvement (QI) project was to increase HBV screening rates in our internal medicine residency program outpatient clinic in accordance with updated CDC recommendations.

Table 1

The number of new patients screened for HBV and the total number of patients screened for HBV, organized by month.

Methods

This QI project took place at a single outpatient internal medicine residency clinic from August 2023 to April 2024. HBV screening rates were obtained at baseline and monthly thereafter. All patients 18 years and older were included unless prior billing and coding data demonstrated a diagnosis of hepatitis B. 2798 patients were identified in the population at the beginning of the study. Patients were deemed as successfully screened if they had a documented HBV triple screen [hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc)]. Two Plan-Do-Study-Act (PDSA) cycles were implemented; the first consisted of resident education and the second was the creation of an electronic medical record (EMR) reminder.

Figure 1

The number of patients screened for HBV by month.

Results

Only 32 patients were screened for HBV at baseline. In the six months following PDSA-1, 50 patients were screened. This brought the total number of patients screened to 82, representing a 156% increase in HBV screening after PDSA-1. In the month following the start of PDSA-2, 89 additional patients were screened for HBV, increasing the overall number screened to 171.

Figure 2

The cumulative number of patients that have been screened for HBV, measured monthly.

Conclusion

PDSA-1 (resident education) showed an initial increase in HBV screening followed by a slow decline in screening over time. This suggests that education may transiently increase screening rates; however, screening will decline over time as the recency effect abates. PDSA-2 (EMR reminder) led to a more rapid increase in screening rates which suggests this may be a more impactful way to quickly identify patients in need of HBV screening. Ongoing data collection is needed to determine if EMR-generated reminders are capable of sustaining screening rates over time.

Disclosures

All Authors: No reported disclosures
P-2190. Gender Differences in Hepatitis C Treatment in the New York City Jail System, 2019-2023
Authors: Enemchukwu Chibuzo U , Simonson Raphael , Koenigsberg Batya , Varela Natalia Gonzalez , LaPene Jacqueline , Figueroa Richard , Wiersema Janet
Published: January 2025

Background

Little is known about Hepatitis C (HCV) care outcomes among women experiencing incarceration. Women make up only 7% of the New York City (NYC) jail population, but represent 18% of individuals diagnosed with active HCV. This study examines progress through the HCV care cascade among women and men in the NYC jail system and describes potential gender-related factors in cascade outcomes.

Methods

Persons admitted to the NYC jail system and who completed a medical intake between October 2019 and December 2023 were included in this retrospective cohort analysis. We constructed a care cascade describing rates of universal opt-out HCV screening, confirmatory testing, diagnosis, linkage to jail-based clinical HCV care, and jail-based HCV treatment among the jail population stratified by documented gender. Demographic characteristics and medical history were also examined and stratified by documented gender.

Results

71,130 persons were included in our analysis, of whom 5,085 (7.1%) were women and 66,045 (92.9%) were men. Compared to men, women were screened at higher rates (88.7% vs. 28.1%; p< 0.001), underwent confirmatory testing at lower rates (9.6% vs 11.2%; p=0.002), and had similar rates of active HCV (51.2% vs 47.8%; p=0.22). Women with active HCV were seen by an HCV clinician at similar rates as men (55.4% vs. 59.6%; p=0.32) but initiated HCV treatment at nearly half the rate of men (15.3% vs. 30.3%; p< 0.001). Additionally, women in the NYC jails had significantly higher rates of homelessness (23.5% vs. 19.5%), HIV (3.7% vs. 2.7%), mental health needs (53.7% vs. 30.8%), and history of select substance use disorders (58.6% vs. 45.8%) when compared to men (p< 0.001).

Conclusion

Large HCV treatment gaps exist between women and men experiencing incarceration. Disproportionally higher rates of comorbid medical, mental health, and substance use disorders and more re-entry support needs likely contribute to treatment disparities. Gender-specific strategies centered on the needs of women with justice involvement are needed to enhance the equitable uptake of jail-based HCV treatment. Enhancing treatment access for all persons with justice involvement is critical for HCV elimination efforts.

Disclosures

All Authors: No reported disclosures
P-2223. Plasma Microbial Cell-free DNA Next-generation Sequencing can be a Useful Diagnostic Tool in Patients with Osteoarticular Infections
Authors: Petri Francesco , Mahmoud Omar , Ranganath Nischal , El Zein Said , Igwilo-Alaneme Rita , Abu Saleh Omar M , Berbari Elie , Fida Madiha
Published: January 2025

Background

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

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

Methods

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

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

Results

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

Table 3

Factors associated with diagnostic certainty categories

Conclusion

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

Figure 1

Distribution of KT results and their respective outcome according to the final diagnosis of suspected OAIs cases.

Disclosures

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

Background

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

Methods

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

Results

The 95% limit of detection was determined to be 7-10 genomes/reaction by testing remnant DNA eluates spiked with TP gDNA. Assay specificity was evaluated by testing synthetic DNA targets representing non-cultivable targets and residual clinical samples containing DNA from 114 clinically relevant microbes, including non-TP spirochetes, bacteria, fungi, and viruses. TP-LAMP detected 100% of whole blood samples spiked with 120-125 organisms/mL; 88% of samples with 85 organisms/mL; and 80% of samples spiked with 60 organisms/mL.

From 09/2022 - 07/2023 TP-LAMP had 110 results in non-blood samples and the mean TAT was 4.7 days. Orthogonal diagnostic results were available for a subset of 34 samples. In this group the assay was 100% sensitive and specific with 7 positive tests, comprising 2 cases of primary and 5 cases of secondary syphilis. Three tissue specimens with negative TP-LAMP results had false-positive immunohistochemical TP stains due to cross-reactivity with commensal treponemes.

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Treatment escalation was defined as the broadening of antimicrobial coverage due to KT results. Treatment de-escalation was defined as narrowing/discontinuation of antimicrobial coverage due to KT results.

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

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

Background

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

Methods

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

Results

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

Conclusion

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

Disclosures

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

Background

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

Methods

This is a single center, matched retrospective case control study of KTR with SPBK compared to 1) KTR with low/no BKPyV-DNAemia (LBK) and 2) KTR with high, transient BKPyV-DNAemia (HTBK). Definitions were as follows, SPBK: BKPyV load > 6 log10 for >90 consecutive days. LBK: BKPyV load remaining < 3 log10. HTBK: BKPyV load >4 log10 for < 90 consecutive days, all within the first 2 years post-transplant.

SPBK were exact matched 1:3 to LBK controls on race, sex, donor type immunosuppression protocol, and genetic matched with robust Mahalanobis distance on age. SPBK cases were exact matched 1:2 with HTBK controls on race, gender, immunosuppression protocol, and genetic matched with robust Mahalanobis distance on age and donor type.

Differences between case and control groups were analyzed using Wilcoxon-rank sum test and Fisher’s exact test. A multistate Markov model was used to evaluate whether time spent in a state of lymphopenia (< 1,000 cells/µL) was associated with SPBK.Figure 1A:Total estimated length of stay in a lymphocyte state: SPBK vs HTBK

Results

20 KTR with SPBK were matched to 60 LBK and 40 HTBK. Significantly more SPBK experienced acute cellular rejection within the first 2 years of transplant relative to LBK (75% vs 27%, p< 0.001) and HTBK (22%, p< 0.001). SPBK had a longer estimated duration of lymphopenia in the first 200 days post-transplant relative to LBK and HTBK (SPBK: 107.5 days, 95% CI 92.1, 122.7 vs LBK: 68.5 days, 95% CI 55.3, 84.8, vs HTBK 70.3 days 95% CI 58.8, 82.4, Figure 1A-B).

Median eGFR at 6 months post-transplant for SPBK was lower than patients with LBK and HTBK (44 vs 56, p=0.016; 44 vs 60, p=0.004, respectively). Burden of lab draws was significantly higher for SPBK vs LBK and HTBK (69 days vs 55, p< 0.001; 69 days vs 56, p=0.006, respectively). Total cost of labs was $7836 for SPBK vs $4,691 for LBK (p< 0.001) and $5922 for HTBK (p< 0.001).

Conclusion

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

Disclosures

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

Background

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

Box Plot of QFM results according to study timeline

Methods

Prospective cohort study of KTR who were given anti-thymocyte globulin (ATG) induction therapy enrolled in August/2018 to August/2019. QFM tests were collected at the Tx procedure (d0), 30 (d30), 90 (d90) and 180 (d180) days post-Tx and results were presented as medians of INF-ɣ values. Infections were classified in severe (hospitalization), opportunist, bacterial and clinically significant cytomegalovirus events. AR was biopsy proven or defined by treatment with ATG or corticosteroids.

Kinetics Plots of INF-ɣ stratified by Infection episodes and study timeline

A - Medians and interquartile ranges of INF-ɣ release according to study timeline and Severe Infection. B - Medians of INF-ɣ release according to study timeline and Bacterial Infection and C - Medians of INF-ɣ release according to study timeline and Opportunist Infection

Results

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

Kinetics Plots of INF-ɣ stratified by Acute Rejection episodes and study timeline

Conclusion

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

Disclosures

All Authors: No reported disclosures
P-2267. Autopsies: Revisiting the Gold Standard
Authors: Tsai Helen , Minamoto Grace Y , Burack Daniel A , Ramesh Rithva
Published: January 2025

Background

Infections in solid organ transplant (SOT) recipients continue to be a clinical challenge despite modern diagnostics. Autopsies have the potential to identify missed infectious diagnoses thereby informing the practice of transplant infectious diseases. We sought to evaluate the clinical value of autopsies by analyzing pre-and post-mortem infectious diagnoses of deceased SOT recipients.

Methods

We retrospectively reviewed deceased adult SOT recipients who underwent autopsies at our institution from January 2017 to December 2022. Electronic medical chart review of these recipients was conducted to determine the clinical infectious diagnoses during the hospitalization in which death occurred. Autopsy reports were reviewed for post-mortem pathological findings. Patients who expired near admission without clinical information or did not expire from infection were excluded. Two physicians independently reviewed clinical information and pathological data and applied the Modified Goldman Criteria to categorize clinical and autopsy infectious discrepancies.

Results

During the study period, 21 autopsies were performed (Table 1). Pre-mortem infectious diagnoses included bloodstream infections (n = 11), pneumonia alone including 1 case of Rhizopus and 1 case of Pneumocystis (n = 7), CMV viremia (n = 2), cholangitis (n = 1), and sepsis of undetermined etiology (n = 2). In no instances did an autopsy exam reveal an infection undiagnosed pre-mortem, and thus there were no diagnostic errors that met Modified Goldman Criteria. No specific histopathological staining was performed in the cases with CMV viremia or suspected Pneumocystis pneumonia. In the case of Rhizopus, no comment regarding evidence of angioinvasion or extent of infection was made in the autopsy report.

Conclusion

We did not identify any missed infectious diagnoses on post-mortem evaluation that would have impacted management or outcome. These findings emphasize the importance of collaboration between infectious disease specialists and anatomic pathologists to direct histopathologic and microbiologic testing on tissues of clinical interest. Accurate autopsy diagnoses for SOT recipients, who are at risk for opportunistic and emerging infections, can critically advance transplant medicine.

Disclosures

All Authors: No reported disclosures