bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2113. Development of a Local Multidrug-Resistant Gram-Negative Antibiogram
Authors: Crawford Robert , Bunner Courtney , Chin Jacinta , Gould Alyssa P
Published: January 2025

Background

As gram-negative (GN) resistance continues to rise, it is imperative to understand the best empiric treatment options on a local or regional level. Traditional antibiograms including all isolates may be diluted by sensitive organisms that do not have broad spectrum agents automated for susceptibility testing. The purpose of this review was to develop a health system antibiogram and assess susceptibility rates specific to multidrug-resistant (MDR) GN organisms, including newer broad-spectrum agents that are not routinely reported on traditional antibiograms.

Multidrug-Resistant Gram-Negative Antibiogram 2017-2023

Methods

Data was collected from acute care facilities within a large community hospital system. MDR GN isolates including extended spectrum β-lactamase-producing (ESBL) Enterobacterales, carbapenem-resistant (CR) Enterobacterales, difficult-to-treat (DTR) Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia complex from January 2017 to December 2023 were included. Susceptibility testing was completed using VITEK 2 system (bioMérieux), E-test or Kirby-Bauer disk diffusion. Interpretation of susceptibility data was based on CLSI M100 guidance.

Results

The MDR GN antibiogram is shown in Table 1. The most common isolates encountered were ESBL Escherichia coli (n=8797) and ESBL Klebsiella pneumoniae (n=1779). DTR P. aeruginosa had the lowest susceptibility across all agents; in comparison to CR P. aeruginosa isolates, ceftazidime/avibactam susceptibility was similar however ceftolozane/tazobactam susceptibility was lower. Notably, ceftazidime/avibactam (100%) retained activity for CR K. pneumoniae while CR E. coli had a lower than expected isolate count and susceptibility. S. maltophilia had lower reported susceptibility to trimethoprim/sulfamethoxazole and levofloxacin (84% and 86% respectively) than minocycline (95%) which is performed upon request via manual E-test.

Conclusion

Most MDR GN pathogens within a large community hospital system had reported activity to newer antimicrobial agents. Overall, our antibiogram aligns with treatment recommendations advised by IDSA 2023 Antimicrobial Resistance guidance. Next steps include additional data review for annual susceptibility trends.

Disclosures

All Authors: No reported disclosures
P-2115. Clinical Presentation and Outcome of Tuberculosis in Chronic Kidney Disease Stage 4 and 5 from a high TB burden Country
Authors: Samar Rohama , Dodani Sunil , Nasim Asma , Udin Zaheer
Published: January 2025

Background

Diagnosis and management of Tuberculosis (TB) in chronic kidney disease (CKD) is challenging. Our aim is to study clinical presentation and outcome in patients with stage 4 and 5 CKD from a high TB burden country.

Methods

All patients registered from May 2016 to June 2020 were included. Rifampicin resistance on GeneXpert test was excluded. Patients with CKD stage 4 and 5 were studied for demographics, TB history, clinical features, diagnoses, treatment success and mortality. CKD stage 4 and 5 were compared with other patients registered at the TB treatment center.

Results

Out of 828, 259 (31%) had CKD stage 4 and 5. Out of 259, 156 (60%) had extra-pulmonary TB (EPTB). Microbiological diagnosis done in 118 (45.51%), 25% in EPTB and 72.9% in pulmonary TB (PTB). TB culture was positive in 46 (17.8%), Isoniazid resistance [10] 21.7%. Treatment success was 80.7%. PTB was significantly associated with mortality (p=0.031). In CKD stage 4 and 5 treatment success was significantly lower with high mortality (p=0.033).

Conclusion

In CKD stage 4 and 5, EPTB is the most common presentation. Microbiological diagnosis could be achieved in one -fourth of EPTB. There is high INH resistance. The treatment success is low with high mortality and PTB is a significant risk factor for mortality.

Disclosures

All Authors: No reported disclosures
P-21. Comparison of Three RSV Vaccine Lower Respiratory Tract Disease Primary Endpoint Definitions for Adult Vaccine
Authors: Williams Sarah E , Begier Elizabeth , Ilangovan Kumar , Hall-Murray Cassandra , Gessner Bradford D
Published: January 2025

Background

Despite their public health importance, a consensus definition for lower respiratory tract disease (LRTD), or illness (LRTI) is lacking. Clinical trials of three respiratory syncytial virus (RSV) vaccines for older adults used different LRTI/LRTD definitions for vaccine efficacy (VE). We hypothesize differences between definitions could bias product comparisons.Table 1.Variation of signs or symptoms included in criteria to meet case definition of LRTI or LRTD in three RSV vaccine clinical trials

Methods

We reviewed case definitions for LRTI/LRTD in RSV vaccine clinical trials conducted in older adults.Table 2.Specified values for symptoms/signs included in LRTI/LRTD criteria definitions for three RSV vaccine clinical trials

Results

Two of three published RSV vaccine clinical trials from Pfizer and Moderna used two outcomes (LRTI/LRTD with ≥2 signs/symptoms or ≥3 signs/symptoms) to measure VE, while the third trial from GlaxoSmithKline (GSK) used one (combining ≥2 and ≥3 signs/symptoms) (Table 1). The Pfizer trial included 5 signs/symptoms as components of LRTI; three of these (tachypnea, wheezing, shortness of breath) suggest lower airway involvement and two (cough and self-reported sputum production) could also result from upper airway infection. At interim analysis, 29 of 45 cases had only 2 symptoms (64.4%). Of these 29, 25 had only cough and sputum production (86.2%). The GSK trial, by contrast, required all LRTD cases to include at least one sign, all of which indicated lower airway involvement (Table 2). The Moderna trial included 10 signs/symptoms, including the potential for subjects to have only cough and sputum production. Even within signs/symptoms, definitions differed (e.g., tachypnea cutoff ranged from 20 to 25 breaths per minute; Table 2). When using comparable definitions, full season 1 VEs for Pfizer and GSK products were similar while the point estimate for the Pfizer product was higher during season 2 (Table 3).Table 3.Vaccine efficacy for three RSV vaccine clinical trials using study LRTI/LRTD definitions

Conclusion

Lack of standard case definitions limit ability to compare results across trials. Some ≥2 LRTI events for Pfizer and Moderna may not have involved the lower respiratory tract but rather the upper respiratory tract only. The most comparable case definitions likely are ≥3 signs/symptoms LRTI in the Pfizer and Moderna trials, and LRTD in the GSK trial.

Disclosures

Sarah E. Williams, MD, MPH, Pfizer, Inc: Salary|Pfizer, Inc: Stocks/Bonds (Private Company) Elizabeth Begier, MD, M.P.H., Pfizer Vaccines: Employee|Pfizer Vaccines: Stocks/Bonds (Private Company) Kumar Ilangovan, MD, MSPH, MMCi, Pfizer, Inc.: salary|Pfizer, Inc.: Stocks/Bonds (Public Company) Cassandra Hall-Murray, PharmD, Pfizer, Inc.: employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Bradford D. Gessner, M.D., M.P.H., Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
P-2141. Factors Associated With Death in a Population-based Invasive Mold Surveillance Program, Atlanta, GA
Authors: Oliver Nora T , Mackey Carolyn , Goodenough Dana , Thomas Stepy , Witt Lucy S
Published: January 2025

Background

Invasive mold infections (IMI) can lead to severe illness and are associated with high mortality. Using data from a population-based surveillance program, we describe risk factors associated with death in patients with IMI.

Demographic information, total cohort of patients with IMI, N = 236

Methods

The Georgia Emerging Infections Program conducted a CDC-funded active IMI surveillance program at 3 academic hospitals in the Atlanta metropolitan area from 2020-2022. Cases were determined based on EORTC/MSG criteria using supportive culture and Aspergillus galactomannan (serum or BAL) data. Cases were also ascertained if the treating physician provided a diagnosis of IMI and the patient received mold-active antifungal therapy. Variables listed are for 30 days from incident mold specimen identified and 90 days for COVID-19 diagnosis. Descriptive and univariate analyses evaluated risk factors for 90-day mortality after incident mold specimen identified

Risk Factors for Death from Invasive Mold Infection, Univariate Analysis, N = 236

Results

Of 236 patients identified with IMI, average age was 59 years, 134 were White race (56.8%), and 148 (62.7%) were men (Table 1). 109 patients (46.2%) died. Lymphopenia and neutropenia were present in 138 (58%) and 33 patients (13.9%), respectively. SARS-CoV-2 virus infection was found in 43 patients (18.2%). Ventilatory support was used in 89 patients (37.7%), and 133 (56.3%) patients had pulmonary source of IMI (Table 1). The most common identified fungal pathogen was Aspergillus fumigatus (18.6%) followed by other unidentified Aspergillus spp (6.4%), Fusarium (5%), and Scedosporium spp (5%); GM was positive in 92 patients (39%).

Univariate analysis revealed significant association with death in patients with lymphopenia (p = < 0.0001), neutropenia (p = 0.001), ventilator use (p < .0001), and COVID-19 illness (p < .006). Factors not significant for death included age >65 years, race, sex, presence of chronic lung disease, pulmonary source of IMI, and receipt of anti-mold therapy (Table 2).

Conclusion

Among patients with IMI in these 3 Atlanta hospitals from 2020-2022 , death was associated with underlying host factors such as lymphopenia and neutropenia status. Similarly, ventilatory support and COVID-19 illness were also associated with mortality. Further studies will examine these associations and differences between mold infections.

Disclosures

All Authors: No reported disclosures
P-2145. Candida blankii: An Emerging Threat among Hospitalized Neonates of Bangladesh
Authors: Shuvo Tanzir Ahmed , Shaly Nusrat Jahan , Pammi Farhat Jaby , Islam Md Kamrul , Tasnim Adiba , Tabriz Bhuiyan Shams E , Farzana Fahmida Dil , Aleem Md Abdul , Chowdhury Fahmida , Huq Sayeeda
Published: January 2025

Background

Invasive fungal infections (IFIs) cause serious complications and fatality. Despite the severity of such magnitude, the true burden of these infections remains unclear. In LMICs like Bangladesh, there is a lack of surveillance mechanisms to understand the burden of IFIs. Candida blankii (C. blankii) is an emerging clinical pathogen with first reported human infection in 2014 and limited global reports of clinical infection since then. This study aims to investigate the burden on C. blankii along with other IFIs among hospitalized neonates in Bangladesh.

Methods

Since July 2022, a hospital-based IFI surveillance has been ongoing in the neonatal ICU of a tertiary level hospital in Bangladesh. From then until April 2024, 224 patients were enrolled, who were suspected of have IFIs based on predefined inclusion and exclusion criteria. Blood and endotracheal aspirate samples were collected and sent to the laboratory for microscopy, culture and identification using Vitek 2 and Vitek MS automated system. Additionally, antifungal susceptibility testing (AFST) was performed using the Vitek2 system.

Results

Median age of the enrolled neonates were 17 days (IQR:12-21); 67% of them were male. Notably, 76% of these neonates had positive blood cultures for at least one fungal organism. Kodamaea ohmeri was the most frequently identified fungus (52 cases), followed by Candida cifferi (45) and the emerging fungus C. blankii (36). There were only two cases of Cryptococcus laurentii along with other candida species. Mortality rates were highest among neonates infected with Candida cifferi (67%), followed by C. blankii (45%) and Kodamaea ohmeri (36%). Worryingly, C. blankii exhibited high resistance to Amphotericin B (97%) and Voriconazole (69%), potentially limiting effective treatment options.

High Antifungal Resistance

Conclusion

This ongoing surveillance identified a high prevalence of IFIs, particularly caused by the emerging fungus C. blankii. Further research is necessary to elucidate the potential sources and transmission pathways of C. blankii to design targeted interventions to effectively control this emerging threat in this vulnerable population. The surveillance team is actively working with the hospital authorities to identify potential sources and implement strategies to minimize such infections.

Disclosures

All Authors: No reported disclosures
P-2203. High Rate of False Positives in Military Blood Donors Screening Positive for Hepatitis C Virus
Authors: Izurieta Rafaela , Casleton Brian , Phelps Megan , Gella Melita , Rivera Glorimar , Casey Theresa , Osuna Angela , Jung Ga O , Winkler Erin , Yun Heather , Marcus Joseph , Owen Samuel
Published: January 2025

Background

While the overall rates of Hepatitis C virus (HCV) in military populations are low, positive post-donation screening represents the second most common indication for post-donation infectious deferrals in military blood donors. All donors who screen positive are permanently deferred from blood donation, regardless of follow-up testing in clinical laboratories. There is limited data on the follow-up evaluation of these blood donors. This study describes the confirmatory testing, access to appropriate subspecialty care, and treatment of blood donors who screened positive for HCV at a large military blood bank.

Methods

All military blood donors between 2017-2023 at the Armed Service Blood Bank Center-San Antonio were screened for HCV by both antibody tests and nucleic acid tests, with positive antibody screening tests confirmed with an enzyme-linked immunosorbent assay (ELISA). Donors who screened positive had their medical charts reviewed to determine demographic information, follow-up evaluation, and treatment rates. On follow-up clinical diagnostic tests, patients with positive antibodies were determined to true positives (TP) and those with negative antibodies were determined to be FP.

Results

Of the 100,182 blood donors during the study period, 37 (0.04%) screened positive for HCV, of which follow-up information was available for 27 (73%). Of these 27, only 12 (44%) of donors were found to be TP. TP donors were more likely to be older (median 22 [20-29.5] vs. 20 [18-22], p=0.05) and have higher rates of positive nucleic acid testing (58% vs. 0%, p=0.001) after blood donation (Table 1). There was no difference in linkage to both primary and subspecialty care for TP and FP (Table 2). Of the TP, 7 (58%) were viremic, 3 (43%) of which received anti-viral therapy and 4 (57%) were administratively separated.

Conclusion

While HCV is one of the most common infectious reasons for military service members who donate blood to be deferred from future donations, most positive screenings were FP. Future efforts should be made to re-enter these patients with FP screening tests back into the donor pool.

Disclosures

All Authors: No reported disclosures
P-2204. Design and Pilot Implementation of an ECHO Module to Facilitate Treatment of Hepatitis C Virus Infection During Pregnancy
Authors: Yee Lynn , Aronsohn Andrew , Shah Seema , Lee Karen , Rodriguez Isa , Otero Sebastian , Gower Patrick , Fishbein Joseph D , Johnson Daniel , Jhaveri Ravi
Published: January 2025

Background

Pregnant patients are largely excluded from Hepatitis C virus (HCV) research and treatment. Studies show that pregnant patients want to discuss treatment while providers feel they lack the knowledge and training for these discussions. To bridge this gap, we designed an ECHO module about management of HCV in pregnancy and infancy.

Pre- and Post-surveys of Self Efficacy

Increase in self-efficacy scores after participation in the ECHO module about HCV care during pregnancy

Methods

Content experts from pediatric infectious diseases, hepatology, maternal-fetal medicine, bioethics and members of ECHO-Chicago discussed: prior data, potential topics, target audience and scheduling of sessions. We held 8 one-hour sessions with 20-30 minutes of didactics and 30-40 minutes of solicited case discussion. Participants included those who participated in prior ECHO training and prenatal providers in local and regional practices. A 7-point Likert scale pre- and post-training survey was administered to assess metrics of self-efficacy for management of HCV in pregnancy and childhood.

Results

The sessions were conducted from May-June 2023 on the following topics: HCV screening; HCV pathophysiology/clinical presentations; staging fibrosis in HCV; HCV Treatment in non-pregnant patients; harm reduction; clinical considerations of HCV in pregnancy; shared decision-making for HCV treatment in pregnancy; and HCV screening in infants & treatment for children. Fourteen participants completed pre- and post-surveys. In the pre-survey, participants had low ratings of self-efficacy (average 3.0). In the post-survey, participants reported dramatic increases in all areas (average 5.2, increase of 2.2) with the largest in the following areas: “Ability to discuss and manage timing of hepatitis C treatment in a pregnant person”, average 5.1, increase of 3; “Ability to identify suitable pregnant candidates for treatment for Hepatitis C”, average 5.2, increase of 2.7. For context, a 1-point increase in self-efficacy is considered meaningful. All respondents reported increased ability to address HCV in a preconception, pregnant, postpartum, or neonatal population.

Conclusion

As pivotal studies of pan-genotypic antivirals indicate efficacy and safety during pregnancy, this ECHO module could be distributed to support providers who are discussing therapy initiation.

Disclosures

Ravi Jhaveri, MD, AstraZeneca: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Grant/Research Support|Pediatric Infectious Diseases Society: editorial stipend|Sanofi: Advisor/Consultant|Seqirus: Advisor/Consultant|UpToDate: royalties
P-2207. HCV Reinfection is Associated with Cocaine Use and Ongoing Injection Drug Use in People with OUD: Outcomes from the ANCHOR and LOOP Studies
Authors: Liu Tina , Omari Habib , Ebah Emade , Eyasu Rahwa , Ogbumbadiugha-Weekes Onyinyechi , Cover Amelia , Davis Ashley , Zoltick Meredith , Silk Rachel , Derenoncourt Meghan , Salifu Dorcas , Ghale Sabina , Bijole Phyllis , Jones Miriam , Kier Randy , Sternberg David , Kattakuzhy Sarah , Rosenthal Elana S
Published: January 2025

Background

Despite achieving sustained virologic response (SVR), people with HCV, opioid use disorder (OUD) and ongoing injection drug use (IDU) remain at risk of reinfection. Identification and retreatment of reinfected individuals is critical to HCV elimination. We sought to evaluate the rate of HCV reinfection, factors associated with reinfection, and retreatment in a cohort of people who inject drugs (PWID).Table 1.Bivariate analysis of baseline sociodemographic characteristics.

Methods

The ANCHOR study provided HCV treatment for 198 people with chronic HCV, OUD, and recent opioid use. Those who achieved SVR underwent screening for HCV reinfection, with retreatment initiated per standard of care. At each visit, surveys were administered to evaluate ongoing risk behaviors and medication for OUD (MOUD) status. Patients were followed for 96 weeks with optional enrollment in a 2-year extension study (LOOP).Table 2.Bivariate (IRR) and multivariable (aIRR) analyses of factors associated with HCV reinfection.

Results

158 individuals achieved SVR and were followed after treatment completion for 353 person-years, median 90 weeks (IQR 84-160 weeks). Subjects were predominantly male (69%), Black (84.2%), middle-aged (58 years), and HIV-negative (94.9%). Twenty individuals (12.7%) were reinfected a median of 77 weeks (IQR 60-105 weeks) after HCV treatment, at a rate of 5.7/100 person-years. Reinfection was associated with cocaine use (p< 0.001) and IDU in the past month (p=0.005).

Of the 20 reinfected individuals, 16 (80%) initiated HCV re-treatment a median of 26 weeks after detection (IQR 4-64 weeks), with 12 (75%) achieving SVR, 1 currently on treatment, and 5 deaths.Figure 1.Kaplan-Meier reinfection free survival curve assessing associations of cocaine use with HCV reinfection.

Conclusion

In this cohort of people with OUD recently cured of HCV, we observed moderate rates of HCV reinfection associated with cocaine use and past month IDU, with high rates of retreatment uptake and SVR. These data highlight that in people with active drug use, longitudinal follow-up for retesting and retreatment is critical for HCV elimination. Enhanced accessibility to and engagement with harm-reduction services – such as syringe service programs - and interventions specifically addressing polysubstance use are crucial to reducing ongoing HCV transmission and reinfection.

Disclosures

Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support
P-2209. Hepatitis B Immune Globulin Utilization in Patients Presenting to the Emergency Department Following Sexual Assault
Authors: Zimmerman David E , Rech Megan A , Acquisto Nicole M , Covvey Jordan R , Howington Gavin T , Woolum Jordan A , Slocum Giles W , Flack Tara , Ray Lance , Porter Blake , Kum Vivian , Faine Brett
Published: January 2025

Background

Sexual assault is an unfortunately common in patients seen in the emergency department (ED). Following sexual assault, patients are at risk of several transmissible infections, including hepatitis B virus (HBV). HBV screening, vaccination, and treatment with hepatitis B immune globulin (HBIG) is recommended in select scenarios by the Centers for Disease Control and Prevention (CDC). HBV vaccine should be administered if the assailant’s HBV status is positive or unknown and the patient has not been previously vaccinated. HBIG administration is recommended if the assailant is known to be HBV positive and the patient has not been previously vaccinated. However, there is a paucity of evidence on compliance with these recommendations in the ED.

Methods

This was a multi-center, retrospective cohort study utilizing the Emergency Medicine Pharmacotherapy Research NETwork (EMPHARM-NET). Patients aged 18 or older were included if they had an ED visit with an ICD-10 diagnosis code corresponding to sexual assault from January 1st, 2021 to January 1st, 2023. The primary endpoint was the number of patients who received HBIG in the ED following sexual assault. Secondary endpoints were the proportion of patients with HBV testing performed and HBV vaccine administration.

Results

A total of 952 patients were included across nine EDs. The HBV status of the assailant(s) was unknown in most patients, 942 (98.9%), negative in 10 (0.1%), and zero confirmed positive assailants. Eight patients (0.8%) received HBIG while in the ED. Regarding HBV vaccination status, 327 (34.3%) patients were previously vaccinated while 108 (11.3%) and 510 (53.5%) did not previously receive or their vaccination status was unknown, respectively. Of the 618 (64.9%) patients who did not have a documented HBV vaccine or the status was unknown, 44 (7.1%) received HBV vaccine while in the ED.

Conclusion

HBIG was rarely administered in the ED due to the difficulty in determining the assailants’ HBV status. The recommendations provided by the CDC guidelines likely result in the restricted adoption of HBIG among sexual assault patients. Opportunities exist to better protect patients affected by sexual assault whose assailants HBV status is unknown and to increase vaccination.

Disclosures

David E. Zimmerman, PharmD, BCCCP, BCEMP, FASHP, AMDA Biologics Inc: Grant/Research Support Nicole M. Acquisto, Pharm.D., FASHP, FCCM, FCCP, BCCCP, Melinda Therapeutics: Grant/Research Support Giles W. Slocum, PharmD, BCCCP, BCEMP, Novo Nordisk: Advisor/Consultant
P-2220. Real-World Utilization of a Multiplex Pneumonia PCR Panel on Antimicrobial Stewardship and Antibiotic Use
Authors: Keil Elizabeth , Chionglo Alyssa , Siddiqui Javeed
Published: January 2025

Background

In October 2022 the Queen of the Valley Medical Center (QVMC) microbiology department implemented the Biofire® Pneumonia Pathogen Panel polymerase chain reaction (PCR) for identification of viral and bacterial pathogens along with resistance genes. This may aid in improved identification of pneumonia pathogens with a quicker turnaround time. In contrast, respiratory cultures take multiple days to return with both the organism and antibiotic susceptibility, which delays the time to achieving targeted therapy.

Methods

This was a retrospective cohort study from October 2022 to April 2023. Patients were included if they were admitted to QVMC and had a positive pneumonia PCR. Patients were excluded if they were receiving antibiotics for an indication other than pneumonia, if they did not receive antibiotics, or if they were discharged, transferred or died prior to the PCR result. The primary outcome was if the patient achieved targeted therapy. Secondary outcomes included time to targeted therapy, actions performed based on the results, and correlation between respiratory culture results and PCR.

Results

Fifty-nine patients were included for analysis. Most patients had a diagnosis of CAP (n = 43, 72%), vs. HAP (n = 8, 14%), and VAP (n = 8, 14%). Targeted therapy was achieved in 41 patients (70%). Seven (12%) of these patients had empiric therapy which was also targeted therapy. The mean time from PCR collection to the start of targeted therapy was 23.11 hours. For patients who had respiratory cultures collected, the mean time to final identification with susceptibilities was 40.6 hours. Therefore, targeted therapy was achieved at least 17 hours sooner than if de-escalation or escalation was solely dependent upon respiratory culture results. There were 47 antimicrobial stewardship recommendations documented, and 31 (66%) were accepted by providers. Forty-four patients (75%) also had respiratory cultures collected, and only 19 (43%) had organism growth.

Conclusion

Utilizing multiplex PCR technology for patients with pneumonia can be useful for antimicrobial stewardship programs by providing higher rates of pathogen identification and resistance data compared to respiratory culture alone. This allows for improved time to targeted therapy.

Disclosures

All Authors: No reported disclosures
P-2240. Metabolomic Approaches to Detect Implant-Associated Infections in Post-Mastectomy Women
Authors: Wildenthal John A , Olsen Margaret A A , Tran Hung , Robinson John I , Warren David K , Henderson Jeffrey P
Published: January 2025

Background

This year, approximately 54,000 women with breast cancer will undergo mastectomy followed by implant-based immediate breast reconstruction. This procedure has high infection rates of up to 20% and a diverse microbiology of infection including both gram-positive and gram-negative organisms. Culture-based diagnostic methods after these procedures suffer from poor sensitivity due to antibiotic administration prior to cultures, infection with fastidious organisms, and sequestration of bacteria in implant-associated biofilms. Culture-independent diagnostic methods may serve as an alternative for fast, more accurate diagnosis of these infections.

Methods

Women undergoing implant-based immediate breast reconstruction were recruited. Seroma fluid was collected from the breast pocket at the time of implant removal due to infectious complications, non-infectious wound complications, or at the time of second stage reconstruction. Samples were analyzed using untargeted liquid chromatography/mass spectrometry (LCMS). Differential Compositional Variation Machine Learning (DiCoVarML) was used to discover metabolic features to differentiate infection status in this population.

Results

80 seroma fluid samples taken at time of implant removal were analyzed. Of these, 37 samples were collected at the time of implant removal due to infection, 7 for non-infectious complications, and 36 were collected at the time of second stage reconstruction. After LCMS, 3663 high-quality features were detected in at least ten samples. Features useful in distinguishing infection status were selected using DiCoVarML. Predictive models were able to reliably distinguish infection status, with an area under the receiver operating characteristic curve of ∼0.85. Many features positively correlated with infection are structurally similar to peptides.

Conclusion

Metabolite-based diagnostic methods appear to be promising tools to diagnose infection in immediate breast reconstruction. Features associated with infection may represent small immune proteins/peptides or degradation products from host or pathogen proteases. Further analysis is ongoing to fully identify metabolites associated with infection.

Disclosures

Margaret A A. Olsen, PhD, MPH, Pfizer: Advisor/Consultant|Rebyota: Advisor/Consultant
P-2246. Diagnostic Performance of a Rapid Host-Protein Test (MeMed BV) In Detecting Bacteremia in Children
Authors: Kellerman Lior , Eden Eran , Gottlieb Tanya , Navon Roy , Stein Michal , Srugo Isaac , Esposito Susanna , Papan Cihan , Tenenbaum Tobias , Bont Louis J , Klein Adi , Bachur Richard
Published: January 2025

Background

The gold standard for detecting infections associated with bacteremia is blood cultures. Blood culture yield is low, contamination is frequent and results take 12-48 hours.

MeMed BV® is a rapid, FDA-cleared, host-protein test to differentiate bacterial and viral infection, with sensitivity and specificity >90%, and negative predictive value >98%. Here, we assessed its performance in detecting bacteremia in children as early detection of invasive infections is paramount.

Methods

Multi-cohort analysis of 7 prospective diagnostic accuracy studies of febrile children with suspected infection at the Emergency Department and inpatients. Eligibility required inclusion in the original study, age 3 months to 5 years and blood culture ordered.

Reference standard infection etiology was adjudicated by 3 experts based on review of comprehensive patient data including clinical outcomes. Experts were blinded to MeMed BV results. Cases with bacterial reference standard and positive blood cultures adjudicated as having non-contaminant growth were defined as bacteremia.

Results

1987 patients were studied. The median age was 1.3 years (interquartile range 0.8-2.4); 54.6% were male and 46.7% were hospitalized. The most common ED discharge diagnoses were viral infection (33.6%), upper respiratory tract infection (20.0%), lower respiratory tract infection (16.1%). The prevalence of bacterial infection was 15.4%. MeMed BV diagnostic performance was evaluated against the reference standard and attained sensitivity of 89.9% (95%CI 85.6-93.0), specificity of 94.3% (95%CI 93.0-95.4), and NPV of 98.1% (95%CI 97.3-98.7) for identifying bacterial infection.

19 (1%) patients had bacteremia; among these, MeMed BV identified 14 with bacterial scores, 2 with equivocal scores, and 3 with viral scores, the latter positive for Kingella kingae (see Table for more details).

Conclusion

MeMed BV can aid in early detection of bacteremia in children.

Disclosures

Lior Kellerman, M.D, MeMed: Employee|MeMed: Stocks/Bonds (Private Company) Eran Eden, PhD, MeMed: Employee|MeMed: Stocks/Bonds (Private Company) Tanya Gottlieb, PhD, MeMed: Employee|MeMed: Stocks/Bonds (Private Company) Roy Navon, MSc, MeMed: Employee|MeMed: Stocks/Bonds (Private Company) Richard Bachur, MD, MeMed: Advisor/Consultant|UpToDate - WoltersKluwer: Advisor/Consultant|UpToDate - WoltersKluwer: Royalties - Editor
P-2252. Bloodstream Infections in Heart Transplant Recipients Following the 2018 OPTN Heart Allocation Policy Change
Authors: Mezochow Alyssa K , Pereira Marcus R , Ortega-Legaspi Juan , Lautenbach Ebbing
Published: January 2025

Background

In 2018, the Organ Procurement and Transplant Network (OPTN) changed the United States’ heart allocation policy to prioritize candidates requiring temporary mechanical circulatory support (tMCS), resulting in more orthotopic heart transplant (OHT) candidates transplanted on tMCS. Use of tMCS is associated with nosocomial infections in non-transplant patients, including bloodstream infections (BSI). However, this is not well studied in the OHT population. This study aimed to explore changes in BSI rate in OHT recipients following the 2018 policy change.

Methods

This was a single center retrospective cohort study of OHT recipients at a large quaternary care medical center from 1/1/2015-12/31/2022. Recipients were followed for 90 days after OHT for initial BSI. BSI organisms were categorized based on microbiology and commensal organisms were classified per the Centers for Disease Control and Prevention definition.

Results

There were 441 OHTs during the study period with 232 (52.6%) OHTs occurring prior to the policy change in 2018. Demographics of recipients did not significantly differ over this period. Overall, 7.5% (N=33) of recipients in the cohort developed a BSI post-transplant. BSI in the cohort were due to 12 unique organisms (Table 1). Nearly half were Gram-positive (48.5%), while Gram-negative and fungal organisms made up a smaller proportion (27.3% vs 24.2%). Recipients in the cohort post policy change had twice the rate of BSI as compared to those transplanted pre-change (10.1% vs 5.2%, P=0.039). Median time to BSI post-transplant in the cohort following the policy change was 11.5 days (IQR 8-18.5), which was similar to prior to the change (14 days, IQR 8-30.5). Fungal infections were more common in the earlier cohort, while Gram-positive infections were more common in the later cohort (Figure 1). Infections with commensal organisms also occurred more frequently in the later cohort (25% vs 48%).

Conclusion

Post-transplant BSI were more common among OHT recipients transplanted after the 2018 allocation policy change. Gram-positive BSI were most common with commensal organisms causing more BSI in the later cohort. Further multivariable analysis and multicenter studies are needed to explore the possible reasons for the increasing BSI rate seen following the policy change.

Disclosures

Marcus R. Pereira, MD, MPH, FAST, Clirnet: Advisor/Consultant|Synklino: Advisor/Consultant|Takeda: Advisor/Consultant Juan Ortega-Legaspi, MD, PhD, Impulse Dynamics: one time paid speaker
P-34. Patients’ Survey of Human Papilloma Virus Vaccination among Systemic Lupus Erythematosus Patients in Japan after Suspension of Proactive Recommendation
Authors: Kurita Takashi , Yamamoto Akio , Hosoya Tadashi , Tsuchida Marina , Yasuda Shinsuke , Gu Yoshiaki
Published: January 2025

Background

Systemic lupus erythematosus (SLE) patients are known to have a high incidence of cervical cancer. The main reason for this is considered to reflect the high rate of Human papilloma virus (HPV) infection and inadequate HPV clearance due to immunosuppressive status. Japan has been facing a problem of low HPV vaccination rates due to the suspension of proactive recommendations for routine HPV vaccination for more than eight years because of the negative media campaign. The objective of this study is to identify the factors that inhibit HPV vaccination among SLE patients to develop strategies for improving HPV vaccination rate.

Figure

Sources of medical information for HPV vaccinated and unvaccinated participants. We asked which informational tools participants use to gather medical information. The most trusted sources are indicated by dark bars; others are indicated by light bars.

* indicates significant differences between HPV vaccinated and unvaccinated participants (p<0.05, chi-square test). (a): Answers by HPV vaccinated participants. (b): Answers by HPV unvaccinated participants.

HPV, Human papilloma virus; SNS, Social networking service; TV, Television

Methods

We conducted a questionnaire survey of female SLE patients aged 18-45 years attending our hospital to analyze factors related to HPV vaccination.

Results

We obtained responses of 83 participants. Only 5 (6.0%) were received HPV vaccination, 15 (18.1%) were uncertain of their vaccine history, and 27 (32.5%) had never even heard of HPV vaccination. The reasons for unvaccinated against HPV were "don't know" with 24 participants, "missed opportunity" with 15, and "troublesome, somehow" with 8. The most trusted source of medical information for the unvaccinated was their physician (47, 60.3%) (Figure). Among the unvaccinated, those who wished to be vaccinated in the future were positively correlated with “trust of vaccine benefit” (r=0.515. p=0.014) and “accurate knowledge about HPV vaccine” (r=0.614, p=0.002), and negatively correlated with “negative attitudes toward vaccination and vaccine policy” (r=-0.562, p=0.007).

Conclusion

HPV vaccination rate among SLE patients in Japan was extremely low. The main reason was lack of knowledge. The most effective solution is considered to provide accurate information and adequate recommendations of HPV vaccination by attending physicians.

Disclosures

Yoshiaki Gu, MD, PhD, MPH, MSD K.K.: Grant/Research Support
P-2285. Factors Associated with Chagas Reactivation After Heart Transplantation: Retrospective Analysis at a Large Volume Academic Transplant Center
Authors: Beaird Omer E , Multani Ashrit , Gaynor Pryce , Yanagimoto-Ogawa Lauren , Fraschilla Stephanie , King Maya , Smith Jonathan G , Nsair Ali , Carlson Margrit , Kubak Bernard M , Schaenman Joanna M
Published: January 2025

Background

Chagas cardiomyopathy (CC), caused by Trypanosoma cruzi, is a common indication for orthotopic heart transplantation (OHT) for patients born in Latin America, however post-transplant Chagas reactivation (CR) is common, occurring in ∼60% of cases. Serial T. cruzi PCR monitoring post-OHT with pre-emptive therapy is the current standard for managing post-transplant CR in part due to poor tolerability of benznidazole and nifurtimox. While this approach is often effective, poor accessibility can create delays in treatment, leading to adverse outcomes. We examined patients with CC who underwent OHT to evaluate factors associated with CR.

Methods

We conducted a retrospective review of all patients with CC who underwent OHT at our center between January 2011 – May 2024, reviewing demographics, pre-transplant desensitization, induction and maintenance immunosuppression, rejection history, and presence or absence of azole prophylaxis.

Results

24 patients with confirmed CC were identified, whose characteristics are listed in Table 1. CR occurred in 5 (20.8%) patients, of whom 2 developed clinical manifestations. Asymptomatic CR occurred in 1/20 patients (5%) on azole prophylaxis, whereas 4/4 (100%) patients not on azole prophylaxis had CR (p< 0.001). Age, sex, induction immunosuppression, and treatment for rejection were not significantly associated with CR. Comparison of patients with and without CR is shown in Table 2.

Conclusion

The rate of CR in our cohort was lower than expected based on published data. This may be related to the use of azole prophylaxis which we frequently use for prevention of coccidioidomycosis. Azoles have varying in vitro and in vivo antitrypanosomal activity. In randomized clinical trials (RCTs), posaconazole demonstrated ability to suppress molecular detection of T. cruzi. Our findings suggest that azole prophylaxis, including fluconazole, may have a protective effect against CR. Considering favorable cost and tolerability of fluconazole as compared to benznidazole and nifurtimox, these findings could have significant implications for post-transplant management of CC. Given the small number of patients with CR in our cohort, larger studies including RCTs are needed to validate this observation.

Disclosures

Joanna M. Schaenman, MD, PhD, FAST, Eurofins Viracor: Honoraria|F2G: Grant/Research Support|MedCure: Advisor/Consultant|Moderna: Clinical trial support to institution|OneLegacy: Advisor/Consultant
P-37. Factors Associated with Healthcare Professionals’ RSV Older Adult Vaccination Knowledge and Practices During the First Season of Vaccine Availability in the United States
Authors: La Elizabeth M , Sweeney Carolyn , Singer David , Davenport Eric , Calhoun Sarah , Harmelink Andrea
Published: January 2025

Background

In 2023, respiratory syncytial virus (RSV) vaccines were approved by the United States (US) Food and Drug Administration (FDA) for adults aged ≥60 years and recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) using shared clinical decision-making (SCDM). This study evaluated healthcare professional (HCP) characteristics associated with RSV vaccination knowledge and practices.

Methods

A cross-sectional online survey targeting approximately 600 HCPs was conducted in November 2023 to assess HCP knowledge, attitudes, and practices related to older adult RSV vaccination. Three logistic regression models used these survey data to explore HCP characteristics associated with RSV vaccination knowledge and practices (e.g., likelihood of knowing FDA indication and ACIP recommendation). The models included HCP type as a covariate a priori, with other covariates determined using backwards selection with a prespecified stay criterion (P < 0.1).

Results

The survey was completed by 603 HCPs (Table 1). HCPs had higher odds of being knowledgeable about the FDA indication and ACIP recommendation for older adult RSV vaccination if their workplace stocked RSV vaccine(s); odds were lower if HCPs were least familiar with RSV disease or had a higher percentage of non-White adult patients (Table 2). Odds of initiating RSV vaccination conversations with ≤5% of older adult patients were higher among HCPs who were less familiar with RSV disease, felt less confident in SCDM conversations, and perceived RSV protection to be less important than other respiratory infections (Table 3). Being less familiar with RSV disease was also associated with higher odds of not recommending/administering RSV vaccines to any older adults in the past 3 months (Table 4).

Conclusion

HCP familiarity with older adult RSV disease was associated with RSV vaccination knowledge and practices, highlighting the importance of continued RSV disease awareness efforts. Results can be used to tailor these efforts towards HCPs with potential vaccination knowledge and practice gaps to help ensure equitable RSV vaccination access across older adults.

FUNDING: GSK (study identifier: VEO-000726)

Disclosures

Elizabeth M. La, PhD, GSK: employee|GSK: Stocks/Bonds (Private Company) David Singer, PharmD, MS, GSK: employee|GSK: Stocks/Bonds (Public Company) Eric Davenport, MStat, MEcon, GSK: study funding Andrea Harmelink, PhD, FNP, GSK: Stocks/Bonds (Public Company)
P-2288. Antibiotic Use and Infectious Complications in Hematological Patients Undergoing CAR T-Cell Therapy
Authors: Puerta-Alcalde Pedro , Calbacho Maria , Bailen Rebeca , Martin Ana Africa , Garcia Inmaculada , Puertas Borja , Vilalta Anna , Montoro Mercedes , Anguera Sergi , Ortiz Valentin , Fernandez-Larrea Carlos , Soriano Alex , Garcia-Vidal Carolina
Published: January 2025

Background

Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face significant infection risks. Current data on the frequency and nature of these infections remain limited.

Table 1

Methods

Prospective multicenter cohort including all consecutive patients treated with CD19 or BCMA CAR T-cell therapy from January 2022 to February 2024 in three university hospitals in Spain. All participants provided informed consent and were monitored for 90 days post-treatment.

Table 1 (continued)

Results

A total of 210 patients were enrolled. Demographics, comorbidities, and specific therapy details are outlined in Table 1. Overall, 71% of patients experienced fever at a median of 2 days (IQR 1-3) after CAR T-cell infusion. Antibiotics were administered to 79.3% of patients for a median duration of 7 days (IQR 4-11) with meropenem (57.6%) and piperacillin-tazobactam (40.5%) being the most frequently used. Bacteremia was evidenced in 17 (8.1%) patients, with 6 (2.9%) patients experiencing multiple episodes. The median onset of first bacteremia was 27 days (IQR 16.5-36), with 14/17 (82.3%) episodes occurring over 2 weeks after CAR T-cell infusion. Predominant pathogens were P. aeruginosa (5, 2.4%), coagulase-negative staphylococci (5, 2.4%), and E. coli (4, 1.9%). Clostridioides difficile infection occurred in 7 (3.3%) patients. Viral infections were reported in 37 (17.6%) patients, primarily due to SARS-CoV-2 (22, 10.5%) and Influenza (6, 2.9%), while fungal infections were noted in 10 (4.8%) patients (4 aspergillosis, 3 candidemia, 1 mucormycosis, 1 other mold, and 1 possible fungal infection). ICU admission was required for 38 (18.1%) patients, with infections prompting 6 of these cases. The 90-day mortality rate stood at 6.2%, with 61.5% of these deaths attributed to infections. Patients suffering any infection (bacterial, viral, or fungal) had significantly higher 90-day mortality (17.2% vs 2.0%, p < 0.001). Table 2 shows the different 90-day mortality rates regarding the type of infection.

Conclusion

Antibiotic use is prevalent immediately following CAR T-cell infusion, despite a low initial bacterial infection rate. Nonetheless, infections within the first 90 days post-CAR-T infusion are common and correlate with worse outcomes.

Disclosures

All Authors: No reported disclosures
P-2294. Listeriosis in cancer patients: Uncommon and protean
Authors: Snellings Robin , Matsuo Takahiro , Wurster Sebastian , Jiang Ying , Tarrand Jeffery , Cho Sung-Yeon , Kontoyiannis Dimitrios P
Published: January 2025

Background

Historically cancer patients (pts) are considered to be at an increased risk of Listeria monocytogenes infection (listeriosis, LT), especially those with ongoing chemotherapy or receipt of glucocorticoids (GCs). However, the features of this uncommon infection have not been described in contemporary cohorts of cancer pts.

Methods

We performed a 12-year retrospective chart review of cancer pts with LT as confirmed by positive culture from blood or other sterile clinical samples at MD Anderson Cancer Center (2011-2023).

Results

We identified 20 cancer pts with LT. Twelve (60%) had an underlying hematologic malignancy (Figure 1). Lymphopenia < 1000/µL (17, 85%, severe < 200/µL in 20%) and monocytopenia < 1000/µL (18, 90%, severe < 200/µL in 35%) were common at diagnosis, as well as chemotherapy (13, 65%) and GC use (11, 55%) within 30 days prior to LT diagnosis. Most (15 pts) were < 65 years old. Fever was seen in 10 pts. Vomiting/diarrhea were common (50%), while 45% of pts had headache or altered mental status. LT most often presented with bacteremia (17, 85%) and gastroenteritis (9, 45%) (Figure 2). 7/9 pts with gastroenteritis were bacteremic. Central nervous system (CNS) manifestations (meningitis, brain abscess) were documented in 2 pts who had a lumbar puncture. Focal non-CNS infections were seen in 30% of pts in unusual sites: cellulitis, abscess, endocarditis, cholangitis, urinary tract infection, and peritonitis. Of interest, 11pts (55%) had low SOFA score at presentation and were given antibiotics only after blood cultures were positive for Listeria. In fact, most pts (17, 85%) either did not receive empiric (n=11) or had inappropriate empiric antibiotics (n=6) until LT diagnosis. The 30-day mortality from LT diagnosis was 25% and correlated with high SOFA score ≥ 5 (5/8 pts, P = 0.0005). Delayed appropriate antibiotics were not significantly associated with increased 30-day mortality in this small cohort (Table 1).

Conclusion

Although uncommon, LT in cancer pts has pleotropic manifestations and variable morbidity, from non-bacteremic gastroenteritis to septicemia, CNS and non-CNS focal infections. Consider LT in ill cancer pts with lymphopenia/monocytopenia and recent chemotherapy or GCs, especially if they have GI symptoms, even in the absence of fever or CNS involvement.

Disclosures

Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant