bluuebunny/crossref_metadata_2025 huggingface dataset:
P-920. Free-living Ameba Infections Diagnosed by Cell-free DNA Blood Testing – United States, 2018-2023
Authors: Haston Julia C , Imada Erin , Roy Shantanu , Davlantes Elizabeth , Freeland Amy , Ali Ibne
Published: January 2025

Background

Free-living amebae (FLA) including Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri live in soil and water worldwide and cause severe infections in humans. Approximately 15 people in the United States are infected by FLA each year; most do not survive. Early diagnosis and treatment improve outcomes. Targeted testing options for FLA require tissue or cerebrospinal fluid (CSF) and are offered at < 5 laboratories in the U.S., making it challenging to diagnose infections quickly and non-invasively. Detection of FLA infections via cell-free DNA testing of blood (Karius Test®) has increased in recent years.

Methods

The Centers for Disease Control and Prevention (CDC) maintains a database of confirmed FLA cases reported through the CDC FLA Clinical Consultation Service or national surveillance efforts. This database was used to identify and describe cases in which a Karius Test® first detected an FLA infection.

Results

In 2018-2023, 9 U.S. FLA infections were diagnosed with Karius Test® and reported to CDC, including 4 Acanthamoeba, 4 Balamuthia, and 1 Naegleria case. These represent 10% of FLA cases reported to CDC in this timeframe (9/93). Four of these cases were reported in 2023 (22% of FLA cases in 2023), an increase over previous years. FLA had not been suspected in 8/9 cases before receiving results. Eight patients presented with meningitis or encephalitis; 1 had only skin findings. FLA diagnoses were subsequently confirmed by other methods in 7/7 cases for which tissue or CSF was available. Duration from hospitalization or symptom onset to Karius Test® result was 5-14 days. One patient was diagnosed postmortem; the others were initiated on anti-amebic therapy. No patients ultimately survived, though 3 patients were treated for several weeks.

Conclusion

Cell-free DNA testing (Karius Test®) of blood is increasingly being used to diagnose FLA infections. Nearly all patients described were diagnosed by Karius Tests® before FLA infections had been suspected. Early diagnosis can allow early treatment, inform clinical decision-making, and contribute to the further understanding of FLA infections through surveillance. In patients with suspected FLA infections or encephalitis of unknown etiology, Karius Test® may be useful, particularly when tissue or CSF is not available.

Disclosures

All Authors: No reported disclosures
P-923. Characterization of the use of the FilmArray Molecular panel for the diagnosis of central nervous system infection
Authors: zapata Silvana , Roldan Daniel Montoya , Villa franco Pablo , patricia isaza Sandra , Atehortua Santiago , Zapata Carolina , Lopez estrada Carolina , Trompa Iván
Published: January 2025

Background

The Biofire FilmArray® Meningitis/Encephalitis Panel (FAME) has proven to be a valuable tool for etiological diagnosis. Despite this, we know little about its clinical impact.This investigation aims to characterize the clinical, epidemiological, therapeutic variables and outcomes of adults with suspected meningitis and/or encephalitis (ME) who underwent FAME panel, in two 3rd level hospitals in Medellín-Colombia.

Central nervous system infection diagnosis

Definitive diagnosis based on clinical and microbiologic criteria

Methods

Retrospective cohort study in 257 patients over 16 years of age, with suspected central nervous system infection with less than 4 weeks of symptoms who underwent FAME panel. Comparisons were made between those with positive and negative FAME panel results, and a medical record evaluation committee determined whether central nervous system infection was present.

Identification of pathogens by Film Array meningitis encephalitis

Pathogens identified

Results

57.19% (147) of the patients presented central nervous system infection, with 70 patients (26.07%) with a positive FAME panel result; the most frequent involvement being bacterial meningitis 37 (52.9%), and among those with negative FAME panel it was aseptic meningitis 23 (15.64%) followed by meningeal tuberculosis 15 (10.2%). Altered consciousness (74.3%), fever (63.4%) and headache (63.4%) predominated in the FAME-positive group, as did higher cerebrospinal fluid (CSF) leukocyte count, glucose consumption and hyperproteinorrachia (p =0.0001). A positive FAME panel result was associated with greater modification of empirical to definitive antibiotic therapy and discontinuation of unnecessary antibiotics, while negative results were associated with shorter hospital stays, fewer neurological sequelae, and lower antibiotic consumption.

Of the total number of patients with positive FAME, 9 had a CSF leukocytes of less than 5 cells/mm3. Additionally, of the total, eight (8) had pharmacological or disease-related immunosuppression, and only one case had a positive FAME for Varicella zoster without medical or pharmacological immunosuppression with normal CSF.

Conclusion

FAME panel in the appropriate context can provide valuable information for decision-making in patients with suspected central nervous system infection; a rational use and restrictive criteria in prescription could improve the benefits without incurring in excessive costs.

Disclosures

All Authors: No reported disclosures
P-934. Emerging Trends and Challenges in Pediatric Infective Endocarditis: Insights from a Single-Center Observational Study
Authors: Naguthevar Santhanam , Tak Vibhor , Khera Daisy , Didel Siyaram , Abhishek Kumar S
Published: January 2025

Background

Infective endocarditis (IE) in children is rare but challenging, with an incidence of 0.43–0.69 cases per 100,000 children–year. Risk factors include congenital and acquired heart diseases, as well as healthcare-associated acquisition via prosthetic devices

Methods

A prospective study was conducted at AIIMS Jodhpur's Department of Medicine from January 2021 to 2024. It included pediatric patients with suspected infective endocarditis (IE).

Results

In this study, the most common age for pediatric endocarditis was 16-20 years, representing 50% of the patients. Following that, the 11-15 years age group accounted for 20% of cases. Both the 0-5 years and 6-10 years age groups each constituted 15% of the patients.

In the study, 65% of pediatric endocarditis cases were male, and 35% were female. Additionally, 60% of patients had a previous heart disease, while 35% did not. For endocarditis type, 15% were prosthetic IE, and 85% were native valve cases.

In the study, the mitral valve was most commonly affected, accounting for 65% of pediatric endocarditis cases. The aortic valve was involved in 20% of cases, while the tricuspid valve was affected in 10%. A combination of aortic and pulmonary involvement was observed in 5% of the cases.

In the study, culture-negative cases were the most common, accounting for 40% of pediatric endocarditis cases. Following that, both Streptococcus and Burkholderia each represented 15% of the infections. Staph aureus and Libmansack IE were each responsible for 10%, while Acinetobacter baumannii and Bartonella comprised 5% of the cases.

In the study, 80% of pediatric endocarditis patients showed improvement, while 20% unfortunately expired.

Conclusion

This study emphasizes the diagnostic challenges of pediatric IE, with many cases culture-negative and caused by diverse organisms. Predominantly affecting adolescents and those with pre-existing heart conditions, IE in children presents multifaceted complexities, underscoring the need for improved diagnostic and treatment strategies to achieve successful outcomes.

Disclosures

All Authors: No reported disclosures
P-935. Treatment and outcome characteristics in patients with Staphylococcus aureus Infective Endocarditis: A prospective observational study
Authors: Bohra Gopal Krishana , Kumar Deepak , Kaur Navneet , Deora Surender , Choudhary Rahul , Midha Naresh Kumar , Meena Durga Shankar , Khatod Yash , T R Neetha , kanagiri Tejasvi , Tak Vibhor
Published: January 2025

Background

Infective endocarditis (IE) is one of the most serious complication of Staphylococcus aureus bacteremia (SAB) and its incidence is on rise ranging from 10% to 46%.1 When present, it is linked to poor prognosis, with in-hospital mortality ranging from 20% to 30% highlighting to some extent the challenge in clinically diagnosing and treating the disease. 2There is lack of data focusing on the management of such cases in developing countries like India.

The present observational study was carried out to determine the treatment and outcome characteristics in patients with IE due to SAB.

Methods

This was a prospective observational study carried in Division of Infectious diseases, Department of General Medicine, All India Institute of Medical Sciences, Jodhpur between January 2023 to October 2023. All consecutive cases diagnosed in-hospital with SAB related IE using modified Duke’s criteria were enrolled in the study. The demographic and clinical details of each patient, the diagnostic evaluation, treatment given and outcomes were recorded. All these patients were followed at 1 month, 3 and 6 months after discharge.

Results

A total of eight cases of SAB related definite IE were included. The most common presenting symptom was fever, present in all cases. Peripheral signs of IE were observed in only three cases having splinter haemorrhages, Osler’s nodes, and Roth spots. IV drug use, congenital heart disease and hemodialysis dependency were found to be risk factors. All the eight patients received only medical management with 5 of them receiving antibiotic monotherapy and 3 of them receiving combination therapy. The reason for combination therapy was persistent bacteremia, lack of fever defervescence. The duration of therapy varied between 6-8 weeks. Five cases underwent repeat follow – up TEE/TTE revealing no vegetation in 4 cases and reduction of vegetation size in one case. There was no in-hospital mortality seen. At 6 months of follow-up one patient expired which was not attributable to SAB IE. Table 1 summarises the clinical, diagnostic and treatment characteristics of cases.

Figure 1 depicts detailed management of SAB related IE cases

Conclusion

This study underscores multifaceted nature of this disease and the use of systematic approach for its management can improve the patient outcomes.

Disclosures

All Authors: No reported disclosures
P-952. A Proposed National Quality Improvement Curriculum for Pediatric Infectious Diseases Trainees
Authors: Li Caitlin , Alkema Hannah
Published: January 2025

Background

Quality improvement is a required competency for all pediatric fellowships, and this skill set is particularly important for infectious diseases (ID) clinicians. However, almost half of pediatric ID program directors report that they do not have a formal QI curriculum for their fellows.

Proposed Quality Improvement and Patient Safety Framework

Methods

A pediatric infectious diseases attending with fellowship and Master’s level training in QI collaborated with the director of improvement science at a large, standalone pediatric hospital to adapt a successful local QI workshop curriculum to align with the needs of pediatric ID fellows. Pediatric ID programs of varied sizes and geographic locations were identified as test sites so the program could be iteratively improved prior to scaling to the national level.

Results

In current state, the designed curriculum has three sections: Patient Safety, Quality Improvement – Background and Tools, and Quality Improvement – Data and Measurement. Each section is designed to be available as a recorded lecture that can be viewed asynchronously or a set of slides with lecture notes that can be reviewed by the participant at their preferred pace. The curriculum will be presented to pediatric fellows at identified programs and iterated based on their feedback prior to widespread distribution.

Conclusion

A national QI curriculum for pediatric ID fellows fills a current gap in resources available for training the next generation of pediatric ID physicians and will equip them with tools that are critical for many facets of a career in ID.

Disclosures

All Authors: No reported disclosures
P-957. Introducing PrEP to Primary Care: A Resident-Focused Initiative
Authors: Moise Hope Oddo , Bell Maren , Gilbert Danielle , Holmes Daniel , Matrana Dexter , Clement Meredith E
Published: January 2025

Background

Despite studies showing that HIV pre-exposure prophylaxis (PrEP) dramatically decreases risk of HIV acquisition, it is only currently prescribed to 30% of those who could benefit. The buy in of primary care providers (PCPs), who have an essential role as preventionists, is critical for the most successful reach; however, studies have shown that PCPs often do not feel knowledgeable about PrEP or may be uncomfortable discussing sexual activity or HIV. We hypothesized that dedicated PrEP training for PCPs in a resident clinic would increase prescribing habits.

Methods

At an Internal Medicine residency clinic with 73 trainees in New Orleans, LA, a pre-intervention survey was distributed to gauge baseline PrEP knowledge and comfort in discussing sexual practices, HIV status and risk factors. Following the training, residents attended a one-hour PrEP training. A post-training survey then assessed interest and intent to prescribe PrEP. We abstracted primary care clinic records to evaluate PrEP prescribing outcomes post-training, from October 2023 to April 2024.

Results

Forty-four residents completed the pre-training assessment. Most indicated non-routine discussions regarding sexual practices (37/44, 84.1%) and HIV risk assessments (41/44, 93.2%). Many trainees reported being not at all familiar with PrEP indications (40.9%), medications (45.5%), or monitoring (81.8%). Most (61.4%) had never discussed PrEP with clients. 53/73 (72.6%) residents attended the educational session, and 26/73 (35.6%) completed the post-training survey. All of the residents who completed both indicated that the training was informative, and 20/21 (95.2%) reported willingness to prescribe PrEP. In the six months post-training, we found that 11 clients were successfully initiated on PrEP. One client was diagnosed with HIV on intake labs, and 3 clients were found to have sexually transmitted infections, all of whom were treated or referred for treatment.

Conclusion

The results of this initiative’s pre-training surveys highlight a lack of routine sexual health and HIV risk assessments in a resident primary care clinic, as well as deficiencies in education regarding HIV PrEP. Following training, residents began prescribing PrEP, demonstrating promise for scaling such educational programs.

PrEP Primary Care Pocket Card

A pocket card adapted from the CDC PrEP TRAIN module was provided to trainees in the resident clinic. Contains information regarding medications available, contraindications, side effects, laboratory monitoring (on back side), ICD-10 code, etc.

Disclosures

Meredith E. Clement, MD, Gilead Sciences: Grant/Research Support|Viiv Pharmaceuticals: Advisor/Consultant
P-965. Using Simulated Corrective Mentoring to Improve Clinical Decision-Making for Patients with HIV and Identify Drivers for Treatment Choices
Authors: Robinson Katie , Frederick Jennifer , Esgro Robert A , Hegde Bharati , Surich Jennifer
Published: January 2025

Background

Due to the vast number of treatment options for the management of patients with HIV, providers are challenged to optimally individualize treatment based on comorbidities, viral resistance, and patient preferences. The use of corrective mentoring in continuing education (CE), is a proven method to improve clinical decision-making while identifying persisting practice challenges.

Methods

Vindico Medical Education and Syandus developed four virtual clinical scenarios designed to encourage optimal decision-making for patients with HIV by providing immediate feedback via simulated corrective mentoring.

Results

As of April 2024, 220 physicians or advanced practice providers involved in the management of patients with HIV had participated in the simulations. Across simulations, only 27% of initial decisions were optimal. At baseline, the most challenging topics regarding medication management were related to management during pregnancy (33% optimal), initial ART selection (49% optimal), and identifying candidates for injectable therapy (44% optimal). However, after corrective mentoring, there was over a 300% increase in optimal decisions made. Of optimal decisions, 48% of clinicians preferred BIC/FTC/TAF as initial treatment selection for a young male with no comorbidities and 47% preferred this regimen for an older patient with early-stage chronic kidney disease (CKD) and various other cardiovascular comorbidities. However, for a patient who is pregnant, BIC/FTC/TAF was also the preferred regimen, even though at the time of the simulation development there was insufficient data to recommend its use. These findings suggest that comfortability with certain regimens may be a driving force for clinical decision-making, even when those decisions may not be ideal. Drivers of choosing alternatives such as CAB/RPV or DTC/3TC include avoidance of weight gain, reduced pill burden, and later stage CKD.

Conclusion

The use of corrective mentoring in simulation-based CE is an impactful way to encourage clinical decision-making aligned with the latest evidence. Moreover, these data highlight the need to educate clinicians who manage patients with HIV on the importance of individualizing treatment based on patient characteristics.

Disclosures

All Authors: No reported disclosures
P-966. Infectious Disease Enrichment Program: Medical Student Accuracy in Pathogen Identification
Authors: Bernard Lauren , Brown Vincent T , Achufusi Thelma M , Le Nhu , Sherchan Juliana , Widjaja Astrid , Beher Richa , Patel Devang M
Published: January 2025

Background

There has been increased interest in identifying learning strategies that promote long-term retention of medical school content. In 2022, an extracurricular clinical microbiology project called “Pokébug'' was created by the Infectious Disease Interest Group (IDIG) to encourage such retention among preclinical students at the University of Maryland School of Medicine (UMSOM). Students are given “pseudo-case presentations” including five clues such as pathogen route of entry, clinical symptoms, and treatment. At the end of the year, the student with the highest total correct points in each class receives a gift card.Table 1.Medical Student Accuracy in the Pokébug Program

Methods

Here, we studied students’ accuracy as a measure of their long-term retention of clinical microbiology material. Primary aims were to study accuracy: a) overall b) across different pathogen types c) among pathogens that had been learned in class versus not d) temporal variation.

Results

A total of 194 medical students from 3 classes participated in at least one of the 52 weekly quizzes. Students demonstrated marginally higher accuracy among pathogens that had been previously taught in class (87%) versus those they had not (82%). The highest accuracy was observed for parasitic pathogens (95%), while the lowest accuracy was observed for gram positive bacteria (78%). Student accuracy improves over time, which may be due to the project’s incentive structure.

Conclusion

These findings support the conclusion that Pokébug reflects long-term retention of course material and can guide curricula improvements (e.g., additional time could be given to gram-positive bacteria, employ similar active learning strategies in other content areas to strengthen students’ long-term retention). Additionally, IDIG may want to reevaluate the incentive structure to maximize longitudinal student participation.

Disclosures

All Authors: No reported disclosures
P-969. Antibiotic Prescribing Patterns for Surgical Prophylaxis Before and After an Educational Campaign about Penicillin Allergies
Authors: Backus Megan , Romanos Marianne , Wasielewski Anthony , Paz Natalie , Gauthier Timothy
Published: January 2025

Background

Patients with a documented penicillin allergy often do not receive first-line antibiotics for surgical prophylaxis due to the concern for allergic cross-reactivity between cefazolin and penicillins. Receiving suboptimal antibiotics unnecessarily may contribute to increased risk of adverse drug reactions and undesirable clinical outcomes. This study evaluated the rate of first-line antibiotic regimen utilization for surgical prophylaxis in penicillin allergy-labeled patients before and after a prescriber-facing educational campaign about penicillin allergies.Figure 1.WINK Educational Document

Methods

This was a single-center retrospective cohort study conducted at a tertiary care community hospital. Education was provided over one month in-person by infectious diseases and surgical services pharmacists to surgeons and anesthesiologists, including review of an educational handout detailing current penicillin allergy label literature, cefazolin side-chain dissimilarity, and when cefazolin should be considered or avoided (Figure 1). This content was also provided to pharmacists and posted to the system intranet. Patients were included if they had a documented penicillin allergy and received an antibiotic during admission for procedural prophylaxis. Patients receiving systemic antibiotics or with an infection within three days of procedure were excluded. The primary outcome was rate of first-line pre-operative antibiotic regimen utilization for surgical prophylaxis pre-education versus post-education. Secondary outcomes included all-cause hospital readmission within 90 days, acute care length of stay, surgical site infection rate, and safety outcomes. This study was approved by the local Institutional Review Board.Table 1.Baseline Patient Characteristics

Results

340 patients were included in the study, evenly split into the pre- and post-groups. Patient demographics are shown in Table 1. First-line pre-operative antibiotic regimen utilization occurred in 89 patients in the pre-education group (52.4%), and in 113 patients in the post-education group (66.5%) (P = 0.011). Secondary outcomes are listed in Table 2.Table 2.Results for Secondary Outcomes

Conclusion

An educational campaign focusing on reasonable use of cefazolin in the setting of a penicillin allergy label may improve use of first-line antibiotics, which may positively influence clinical outcomes.

Disclosures

Timothy Gauthier, PharmD, BCPS, BCIDP, AbbVie Pharma: Advisor/Consultant|Antimicrobial Therapy, Inc: Advisor/Consultant|Ferring Pharma: Advisor/Consultant|Firstline Mobile Health: Advisor/Consultant|Gilead Pharma: Advisor/Consultant|GoodRx: Advisor/Consultant|GSK Pharma: Advisor/Consultant|Melinta Pharma: Advisor/Consultant|Pattern Biosciences: Advisor/Consultant|Pfizer Pharma: Advisor/Consultant|ProCE: Honoraria|WWW.LearnAntibiotics.com: Ownership Interest
P-979. Clinician Willingness to Consider Long-Acting Therapies and Culturally Supportive Strategies in Caring for Heavily Treatment-Experienced Black, Indigenous, or People of Color (BIPOC) with HIV
Authors: Ackbarali Sumera , Fields Sheldon D , Jain Mamta K , Ogbuagu Onyema
Published: January 2025

Background

Black, Indigenous, or People of Color (BIPOC) are overrepresented among heavily treatment-experienced (HTE) people with HIV (PWH). They face complex treatment challenges, exacerbated by socioeconomic disadvantages, and cultural insensitivities in healthcare settings that lead to suboptimal care and outcomes. To improve clinician competence in integrating long-acting agents into practice and providing culturally supportive care, an educational web-based initiative was designed in collaboration with the Association of Nurses in AIDS Care (ANAC).

Methods

A 60-minute CME activity, led by a multidisciplinary expert panel, was broadcast live on ClinicalSeriesLive and IDCareLive in August 2023 (on-demand until August 2024). Two vignettes of the treatment journey of HTE patients from BIPOC communities (Hispanic & African-American) were utilized to elevate awareness of unique challenges with care. Changes on knowledge/competence pre-/post-test questions and clinician perspectives and challenges (5-point Likert scale) were assessed.

Results

As of April 30th, 2024, 1,728 clinicians participated in these activities (92% were physicians, advanced practitioners, and nurses). Prior to the activity, only 38% of learners had prescribed or administered a long-acting antiviral agent for HTE patients. Patients’ ability to access long-acting antiretroviral (ARV) therapy was the most frequently cited barrier by clinicians when considering this option (43%). Regarding culturally supportive care pre-activity, 12% of learners sought to understand stigma faced by patients within their communities and 11% spoke patients’ languages or referred them to translation services. Post-activity, learners demonstrated increased confidence in selecting a long-acting therapy (59%), discussing options with HTE patients (64%), and developing strategies to deliver more culturally supportive care (73%). Improvements in pre/post paired responses to CME questions are shown in Table 1.

Conclusion

Web-based education on strategies to incorporate long-acting ARV therapies and culturally supportive care can improve clinician knowledge, uncover barriers, and stimulate practice change that improves care of HTE PWH from BIPOC communities.

Disclosures

Mamta K. Jain, MD, MPH, Abbvie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Laurent: Grant/Research Support Onyema Ogbuagu, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Honoraria|GSK/ViiV: Advisor/Consultant|GSK/ViiV: Honoraria|Janssen: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Honoraria
P-993. Increased Reporting of RPR Seronegative Infants with Congenital Syphilis to the Chicago Department of Public Health, A Quality Improvement Project
Authors: Flores John , Ahn Yeo Won , Kasal Nikki , Osayande Osasu , Betz Amy , Bartlett Allison H
Published: January 2025

Background

We are in the midst of an epidemic of congenital syphilis (CS). Nationwide CS diagnosis and treatment recommendations provided by the Centers for Disease Control are dependent on the timing of maternal treatment, and laboratory and procedural results of the mother and infants. There are specific circumstances where infants with a non-reactive rapid plasma reagin (RPR-) should receive a 10-day course of treatment in the context of inadequate maternal treatment. Depending on the institutional reporting practices of CS to departments of public health, there may be scenarios where RPR-based reporting protocols will leave out this specific cohort.

Methods

Baseline data of Infants stratified by RPR status was collected through electronic medical record (EMR) review for those born at the University of Chicago Comer Children’s Hospital in Chicago, IL between January 2011 and December 2022, using billing codes & penicillin administration data. From September 1st, 2023, through March 31st, 2024, a quality improvement intervention was implemented that involved communicating with the hospital’s Pediatric Infectious Diseases specialists, Pediatric & Newborn Hospitalists, Neonatologists, Infection Prevention & Control, and Chicago Department of Public Health (CDPH). The intervention components included 1) formalize expectation to page Pediatric ID on-call team all infants with concern for maternal syphilis exposure, 2) create an Epic Smart Phrase to standardize data presentation for clinical and reporting purposes, 3) standardize ICD-10 diagnosis coding practices, and 4)email reminders monthly to teams involved.

Results

154 infants were identified who had a CDC case definition of CS and received penicillin administration therapy. Infants with CS from 2011-2022 showed 107/154 (69.4%) were RPR- and 41/154 (26.6%) were RPR- and received > 1 day of penicillin. At the end of the first PDSA cycle, a total of 22 infants were reported to CDPH with 36% (n=8) being RPR-.

Conclusion

Our Quality Improvement project identified a large percentage of infants diagnosed and treated with CS who were not reported to the CDPH with our previous RPR-positive – based reporting strategy. We implemented an intervention that successfully improved reporting of this specific type of patient.

Disclosures

Allison H. Bartlett, MD, MS, CVS/Caremark: Advisor/Consultant
P-1000. The Impact of Re-Initiation of Universal Antenatal Screening on the Incidence of Group B Streptococcus (GBS) Infection
Authors: Alruqaie Nourah Ibrahim , Alharbi Musaed , Alqarni Hailah , Alshaalan Mohammed
Published: January 2025

Background

Group B streptococcus (GBS) is a leading cause of neonatal bacterial sepsis and meningitis globally. Despite the similar incidence rate of neonatal GBS infection in Saudi Arabia as compared to other countries, there has been a notable increase in Early Onset Disease (EOD) following the discontinuation of universal antenatal screening. Addressing this issue, we evaluated the incidence of EOD after the re-initiation of universal antenatal screening.

Association of gestational age, diagnosis, and mortality with the onset of GBS

EOD: Early-onset disease

LOD: Late-onset disease

Methods

This study was conducted in a tertiary children's hospital in Riyadh, Saudi Arabia, using a retrospective cohort chart review, which included all cases of neonatal GBS disease identified through microbiology records within the first 90 days of life from January 2017 to December 2023. A standardized form was used to collect maternal and neonatal characteristics by reviewing the charts

Results

Over seven years, of 61,049 live births, 47 cases of GBS disease were identified (overall incidence, 0.77/1000 live births), and 70% (n = 34) of those had early onset disease (EOD). The annual incidence from 2017 to 2020 showed no significant difference compared to the years when the universal screen was discontinued (2015 and 2016). However, a significant drop was noted in the years after (2021 to 2023), in which the incidence rate was 0.23/1000 live births. We found that 64% (n=30) of mothers who had neonates with GBS disease were either not screened antenatally or were un-booked. Additionally, 49% (n=23) of mothers had a positive GBS screen; however, none of them received appropriate antibiotic prophylaxis. Sepsis was the most common manifestation (76.6%, n = 36), followed by meningitis and Urinary tract infection , 15% and 10.6% respectively. Mortality rate was 8.5% (n = 4)

Conclusion

After three years of re-initiation of universal screening, the incidence of neonatal GBS infection has declined and returned to its previous baseline rate, and similar to worldwide incidence

Disclosures

All Authors: No reported disclosures
P-1021. Comparative Clinical profile, Anti-Fungal resistance rates and in-hospital mortality in hospitalized patients with Candidaemia caused by Candida Auris versus Non-Auris Candida in a tertiary-care centre
Authors: Nagvekar Vasant , Bubna Anusha , shivaprakash Shashikala , Shukala Akash , Mohanka Ravi , rao prashtana , Patel Neha , Vaity Charudatt , Malakavalpil Bindu , Pandit Rahul , Pillai Preeti , Borde Omkar , Mundra Neetu
Published: January 2025

Background

Candidemia, a severest manifestation of invasive candidiasis, often encountered in intensive care units (ICUs) is predisposed by prolonged ICU-stay, immunosuppression or mechanical ventilation. In India, while various species of Candida (C. tropicalis, C. albicans, C. auris and others) are involved in candidemia, C. auris is particularly known for displaying higher anti-fungal resistance. We investigated, whether there was a difference in the clinical pattern of candidemia caused by C. auris vs non-auris Candida in our tertiary-care centre.Figure 1.Comorbidities among patients with candidaemia: C. auris group versus non-auris candida group

CANDIDA AURIS VS NON-AURIS CLINICAL RISK FACTORS

Methods

The analysis involved 65 unique episodes (one patient per episode) of documented candidemia in our tertiary-care centre during January 2022 to April 2024. The clinical data was retrieved from the blinded hospital records. The day of admission of patients in to ICU was considered as hospital day-1.

Results

Among 65 episodes, 17 (26.2%) and 48 (73.8%) were that of C. auris and non-auris candida, respectively. The time to blood culture positivity was longer with C. auris cohort compared to non-auris candida cohort (median hospital days 27 vs 19). Total hospitalization days (median) were 49 and 15.5, P value 0.002 respectively. In-hospital mortality was 58% in C. auris group and 62.5% in non-auris candida group. There was more proportion of cancer patients in non-auris candida cohort while use of immunosuppressive drugs was more frequent in C. auris cohort (Figure 1). Resistance rates to fluconazole, amphotericin, and echinocandins were higher in C. auris group (94.5% vs 25%; 70.5% vs 6.3%; 11% vs 2.1%, respectively)..Total Parenteral Nutrition > 5 days (26.2% vs 73.9%) P value 0.38, Transplant Patients (47.05% vs 14.58%) , immunosuppressive drugs (64.7% vs 39.6% ) P value 0.07 and Mechanical Ventilation (88.2% vs 52.1%) P value 0.008 respectively.

Conclusion

C. Auris has emerged as a notorious Non Albicans Candida species with substantial morbidity and mortality suggesting change in the epidemiology of candidaemia. Patients with Candida auris had longer hospital stay and blood to positivity than others. Fluconazole resistance remains highest in candida auris than other species of candida and majority of isolates of C.auris had high MICs for amphotericin B.

Disclosures

All Authors: No reported disclosures
P-1043. Risk Factors for Breakthrough Invasive Mold Infections in Patients with Hematologic Malignancies
Authors: Nair Vaisak O , Gupta Aanchal , Ranganath Nischal , Mendoza Maria A , Nadarevic Ella , Wengenack Nancy , Vergidis Paschalis
Published: January 2025

Background

Invasive mold infections (IMI) lead to significant morbidity and mortality in patients with hematologic malignancies. We provide patients deemed at higher risk mold active prophylaxis but still observe breakthrough IMIs. The purpose of this study was to evaluate risk factors associated with these breakthrough infections.

Methods

We conducted a retrospective cohort study of adult hematologic patients at 3 tertiary care medical centers from November 19, 2011 - August 6, 2021. Only IMI cases defined as proven or probable per EORTC/MSG criteria were included. Patients with IMIs who received a minimum of 7 days of mold active prophylaxis were classified as breakthrough infection. We performed logistical regression analysis to identify risk factors associated with breakthrough IMI.

Results

Majority of cases were probable IMIs, with 16 (28.6%) and 25 (15.7%) proven cases amongst breakthrough and non-breakthrough IMIs, respectively. Many variables indicative of weakened host immune system, including neutropenia and hypogammaglobulinemia, were associated with breakthrough IMIs, albeit not statistically significant (Table 1). Multivariate analysis revealed history of AML (OR 4.20, 95% CI 2.03-8.88; p < 0.001) and receipt of HCT (OR 3.37, 95% CI 1.46-8.11; p = 0.003) to be independent host risk factors for breakthrough IMI. Of all the pathogens, Fusarium (OR 4.38, 95% CI 1.56-12.56; p = 0.005) and Mucorales (OR 5.59, 95% CI 2.11-15.61; p < 0.001) were significantly likely to lead to breakthrough IMIs. 26 (47.3%) of the breakthrough IMIs were on appropriately dosed prophylaxis at the time of infection, with only 9 (16.4%) found to be subtherapeutic (Table 2). Overall, mortality was slightly higher amongst the breakthrough IMIs (51.8% vs 45.9%) but not significantly different (Figure 1).

Conclusion

In our cohort of probable/proven IMIs, we did not observe any significant difference in mortality between patients with breakthrough IMIs and those not on mold active prophylaxis. Even with appropriate prophylactic dosing, breakthrough infections occurred, irrespective of agent. Our study demonstrates that host risk factors and the causative pathogen are clinically more pertinent than the prophylaxis regimen in breakthrough IMIs.

Disclosures

Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support
P-1055. Anti-Toxin B Neutralizing Monoclonal Antibody AZD5148 Provides Protection in a Clostridioides difficile Gnotobiotic Piglet Model
Authors: Tkaczyk Christine , Dayao Denise , Girouard Donald , Godfrey Victoria , Gamson Adam , Stanley Ann Marie , Stepanov Oleg , DiGiandomenico Antonio , Sellman Bret R , Tzipori Saul
Published: January 2025

Background

Clostridioides difficile infection (CDI) cause mild to severe diarrhea and can be life threatening. Because toxin B is a clinically validated target for CDI, we have generated an anti-toxin B neutralizing monoclonal antibody (mAb) AZD5148. We previously demonstrated that AZD5148 administered at 10, 1 and 0.5 mg/kg prevents severe disease development in a gnotobiotic piglet model, which recapitulates the clinical signs and gross pathology observed in human CDI, we compared the protective efficacy of AZD5148 with the clinically approved anti-toxin B mAb bezlotoxumab.

Methods

Piglets were born by C-section and placed in an individual sterile isolator. Animals were first injected intraperitoneally with 0.5 mg/kg of Clostridioides difficile (C. difficile) mAbs or control IgG (c-IgG) and infected orally 24 hours later with C.difficile spores of NAP1/027/BI strain UK6. Weight and stool scores were recorded daily. Non-infected animals were used as comparators. Necropsy was performed after 7 days for colon gross pathology scoring and tissue histopathology analysis. Anti-toxin B pharmacokinetics were measured in sera by ELISA at days 0, 3 and 7.

Results

Infection with C. difficile reduced weight gain compared to noninfected littermates. All infected animals developed mild to moderate diarrhea after 3 days. Piglets treated with c-IgG or bezlotoxumab exhibited signs of severe disease as measured by diarrhea color and texture. Gross pathological examination of colons at necropsy for c-IgG treated-pigs suggested that animals developed similar pathology to that observed during human CDI with mild to severe hemorrhage of the spiral colon, mesocolonic edema and pseudomembrane formation on the descending colon at day 7, along with rectal prolapse in some cases. No significant difference was observed between the c-IgG and bezlotoxumab groups. In contrast, AZD5148 reduced signs of disease severity as measured by diarrhea scores, gross pathology scoring of descending and spiral colons and damage to the gut epithelium along with inflammation.

Conclusion

These data suggest that AZD5148 may offer some therapeutic benefit in preventing CDI in humans.

Disclosures

Christine Tkaczyk, PhD, Astra Zeneca: stocks as employee Victoria Godfrey, MS, Astra Zeneca: stocks as employee Adam Gamson, MS, Astra Zeneca: stocks as employee Ann Marie Stanley, PhD, Astra Zeneca: stocks as employee Oleg Stepanov, MS, Astra Zeneca: stocks as employee Antonio DiGiandomenico, PhD, Astra Zeneca: stocks as employee Bret R. Sellman, PhD, Astra Zeneca: stocks as employee
P-1061. In vitro Activity of Gepotidacin against Klebsiella pneumoniae, Including Molecularly Characterized Fluoroquinolone not Susceptible Subsets Causing Urinary Tract Infections in the United States (2019-2022)
Authors: Mendes Rodrigo E , Beekman Danielle , Hubler Cory , Kimbrough Hank , Kapoor Renuka , Torumkuney Didem , Ryan Arends S J
Published: January 2025

Background

Gepotidacin (GEP) is a novel, bactericidal, first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a unique mechanism of action, distinct binding site and provides well-balanced inhibition (for most uUTI uropathogens) of two different type II topoisomerase enzymes. This study reports the activity of GEP and other oral antibiotics against K. pneumoniae, including molecularly characterized fluoroquinolone (FQ) not susceptible (NS) isolates collected from urinary tract infection (UTI) patients in the US.

Methods

A total of 2,001 K. pneumoniae were collected from 73 sites. CLSI methods were used for both susceptibility (S) testing and MIC interpretation. Isolates with MIC≥0.5 mg/L for ciprofloxacin (NS) and/or ≥1 mg/L for levofloxacin (NS) were screened for FQ-resistance (R) mechanisms (plasmid-mediated quinolone resistance [PMQR]), QRDR mutations, and expression of acrAB and oqxAB by qRT-PCR.

Results

GEP inhibited 94.9% of all these isolates at ≤16 mg/L (MIC50/90 = 4/16mg/L). GEP MIC50/90 against FQ-S isolates was 4/8 mg/L, and other agents showed activity against ≥90% of isolates, except nitrofurantoin (37.4%S). 14.5% (291/2,001) of isolates were screened for FQ-R mechanisms. GEP MIC50/90 against FQ-NS strains was 16/32 mg/L, whereas other agents had S of 5.8–48.5%. GEP had generally similar activity (MIC50/90, 16-32/32-64 mg/L) against isolates with wildtype QRDR and with or without PMQR genes. Most of the isolates (95.2%) without PMQR genes overexpressed oqxAB and/or acrAB, against which amoxicillin-clavulanate and cefazolin (90.3–95.2%S) were active. GEP had consistent MIC90 of 16 mg/L against isolates with distinct QRDR mutations and absence of PMQR genes, whereas other agents had S of ≤68%.

Conclusion

GEP showed activity against FQ-S and FQ-NS K. pneumoniae UTI isolates from the US, in particular against FQ-NS isolates carrying QRDR mutations, where standard oral antibiotics showed limited activity. GEP MICs were not substantially affected by QRDR mutations. Highest MICs were seen against FQ-NS isolates with wildtype QRDR and PMQR genes and/or overexpression of efflux-pump genes. These data support the development of GEP for the treatment of uUTI caused by K. pneumoniae.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Renuka Kapoor, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Didem Torumkuney, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company)
P-1115. COT-832, a Novel Polyene Macrolide Antifungal (II): In Vivo Fungicidal Efficacy against Aspergillus fumigatus and Candida albicans in Mice and Rats Infection Models
Authors: Nishiyama Yuri , Maki Hideki , Yoshida Osamu , Hasegawa Yasushi , Ukai Yuuta , Fukushima Tamio
Published: January 2025

Background

A novel antifungal compound, COT-832 was created by SHIONOGI through modifying Amphotericin B (AmB). Marketed AmB formulations are often discontinued in clinical use due to nephrotoxicity. In this study, we investigated in vivo efficacy of COT-832 against Aspergillus fumigatus (A. fumigatus) and Candida albicans (C. albicans) in mice and rats infection models in comparison with those of Fungizone (FGZ) and AmBisome (L-AMB) at each human clinically equivalent dose (CED) in AUC.

Methods

CED;

Mice (male ICR mice): FGZ;2.2 mg/kg, L-AMB; 7 mg/kg,

Rats (Crl:CD(SD)): L-AMB; 8 mg/kg,

cf. COT-832; 4 mg/kg showed the safety level similar to L-AMB at CED in a rat 2-week toxicology study.

Systemic candidiasis in mice and rats: Conidia of C. albicans were intravenously administered (iv) in immunosuppressed mice. At 2, 24, and 48 hours (h) in mice, 48h in rats post-infection, each compound was administered (iv). Fungal burden in kidney was quantified at 24h post-treatment.

Invasive pulmonary aspergillosis in rats: 104 conidia of A. fumigatus were inoculated intranasally in immunosuppressed rats. At 24h post-infection, each compound was administered (iv). A. fumigatus 18S rRNA in lung was quantified at 24h post-treatment.

Results

Systemic candidiasis in mice: FGZ at CED; immediate death when treatment was initiated at 24 and 48h post-infection. L-AMB at CED; fungistatic when initiated at 24h post-infection. COT-832; fungicidal at 3 mg/kg when initiated at 24h post-infection.

Systemic candidiasis in rats: COT-832 at 2 mg/kg showed fungistatic efficacy comparable to L-AMB at CED, and COT-832 at 4 mg/kg showed 1-log down fungicidal efficacy from initial.

Invasive pulmonary aspergillosis in rats: COT-832 at 2 mg/kg showed comparable efficacy to L-AMB at CED, and COT-832 at 4 mg/kg showed further 1-log down fungicidal efficacy.

Conclusion

In our rodent infection models, COT-832 showed more potent fungicidal effects in systemic candidiasis and invasive pulmonary aspergillosis at a dose with similar safety level to that of L-AMB at a clinically equivalent dose. These results suggest that COT-832 can be a novel antifungal active pharmaceutical ingredient to exhibit potent in vivo efficacy with less safety concerns than L-AMB.

Disclosures

Yuri Nishiyama, MS, Shionogi & Co., Ltd.: employee Hideki Maki, PhD, Shionogi & Co., Ltd.: employee|Shionogi & Co., Ltd.: employee Osamu Yoshida, n/a, Shionogi & Co., Ltd.: employee Yasushi Hasegawa, n/a, Shionogi & Co., Ltd.: employee Yuuta Ukai, MSc, Shionogi & Co., Ltd.: employee Tamio Fukushima, n/a, Shionogi & Co., Ltd.: employee
P-1116. Distribution of Rifaquizinone in Bone, Synovial Fluid and Plasma: A Phase 1 Trial in Patients Undergoing Total Hip or Knee Arthroplasty
Authors: Parvizi Javad , Krueger Chad A , Chen Jing , Wang Huan , Ai Changlin , Geng Guozhu , Ma Zhenkun
Published: January 2025

Background

Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of prosthetic joint infections (PJIs). RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. This study was to evaluate RFQ concentrations in joint synovial fluids and bone tissues, plasma pharmacokinetics (PK), safety, and tolerability of RFQ for injection in adult patients undergoing total hip or knee arthroplasty (THA/TKA).

Methods

This was a single-center, phase 1, open-label study (NCT04294862) conducted in the USA. Eligible patients received a single IV infusion of RFQ 300 mg 2 hours before anesthesia. Bone and synovial samples were collected during the arthroplasty surgery and analyzed for RFQ concentrations.

Results

Between 1 Mar 2021 and 16 Dec 2021, 13 (9 THA and 4 TKA) patients were enrolled in the study. One subject did not receive a full dose of RFQ and was excluded from PK analysis. The mean bone RFQ concentrations were 2650, 1180, 362 and 410 ng/g in acetabulum, femoral head (THA patients), distal femur and tibia (TKA patients), respectively. The mean synovial fluid concentrations of RFQ were 6840 and 1090 ng/mL in THA and TKA patients, respectively. The mean plasma concentration-time profiles were comparable between THA and TKA patients and consistent with the PK profiles in previous studies. Four (30.8%) patients experienced at least one drug-related treatment-emergent adverse event (TEAE). There were no severe TEAEs or TEAEs leading to discontinuation of study drug.

Conclusion

RFQ was safe and well tolerated in THA and TKA patients. The mean bone and synovial fluid concentrations of RFQ at about 2 hours after a single 300 mg infusion were all reached above the MBBC90 (250 ng/mL) level for S. epidermidis. The acetabulum and synovial fluid concentrations in THA patients also exceeded the MBBC90 (2000 ng/mL) level for S. aureus. The local concentrations of RFQ are expected to rise further and exceed the MBBC90 when patients are treated with multiple doses of RFQ.

Disclosures

Javad Parvizi, MD, FRCS, TenNor Therapeutics (Suzhou) Ltd: Investigator Chad A Krueger, MD, TenNor Therapeutics (Suzhou) Ltd: Investigator Jing Chen, Master of Science, TenNor Therapeutics (Suzhou) Ltd: Employee Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Changlin Ai, Master of Medicine, TenNor Therapeutics (Suzhou) Ltd: Employee Guozhu Geng, MD, TenNor Therapeutics (Suzhou) Ltd: Employee Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee