bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1023. Prevalence and distribution of fungal microorganisms among cutaneous specimens submitted to community microbiology laboratories
Authors: Yeung Eugene
Published: January 2025

Background

Not much is known about the local prevalence of cutaneous fungal infections in Canada because these data are not readily available. Knowing the distribution of microorganisms in local settings may help developing guidance for empiric therapy, especially for immunocompromised patients whose cutaneous fungal infections could turn into systemic infections. The current retrospective study aimed to establish the prevalence and distribution of fungal microorganisms among patients who had specimens submitted to community microbiology laboratory for cutaneous fungal culture workups.

Methods

LifeLabs regional microbiology laboratories, connected with 129 collection centers in urban and rural communities in British Columbia, provided reports of isolated fungus from hair, nail, and skin scraping specimens from 1 January 2022 to 31 December 2022. Culture followed by microscopy and/or MALDI-TOF mass spectrometry was routinely used to isolate and identity microorganisms, but nucleic-acid testing was added to help identification if needed.

Results

Among the 20652 cutaneous specimens submitted in a year, 3665 of them were reported to have microorganism growth. The most reported microorganism was Trichophyton species (43.8%), followed by Penicillium species (5.8%), Candida albicans (4.2%), Aspergillus species (3.6%), and Fusarium species (2.8%). Of note, other than Trichophyton species, the other two main dermatophytes Microsporum species and Epidermophyton species accounted for only 0.2% and 0.1% of the positive specimens, respectively. Pseudomonas aeruginosa was incidentally identified in 2.9% of the positive specimens in the fungal culture workups.

Conclusion

Trichophyton species was the most reported microorganism among the hair, nail, and skin scrapping specimens submitted for cutaneous fungal culture workups from communities in British Columbia. Pseudomonas infections, which could present as chloronychia, folliculitis, ecthyma gangrenosum, could be considered in the differential diagnoses of cutaneous fungal infections. The current data will help clinicians to determine the empiric therapy needed based on each patient’s clinical situation.

Disclosures

All Authors: No reported disclosures
P-1024. Fungal Pneumonia and Severe Neutropenia: Risk Factors for Increased 90 Day Mortality
Authors: Handley Guy , Greene John , Cannella Anthony P , Velez Ana , Shah Shivan , Katzman Ju Hee , Pasikhova Yanina
Published: January 2025

Background

Invasive fungal infections (IFI) carry a high mortality risk in hematologic malignancy; the majority being pulmonary infections. Diagnosis is based on consensus definitions of host factors, clinical features and mycologic evidence. In previous studies, increased mortality is associated with delays in therapy and failure of neutrophil recovery; however, use of salvage posaconazole may have improved outcomes. We sought to identify risk factors associated with higher 90-day mortality in these patients.

Methods

Patients at an NCI designated comprehensive cancer center from 06/2021 – 07/2023 with hematologic malignancy, severe neutropenia and a diagnosis of IFI and receiving posaconazole for treatment with verified therapeutic drug monitoring were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors for increased mortality within 90 days of diagnosis of pulmonary IFI. The diagnosis was based on international consensus definitions.

Results

A total of 39 patients were identified. 18 (46.2%) were diagnosed with acute myeloid leukemia and 13 (33.3%) had undergone bone marrow transplantation. Median time from diagnosis to treatment initiation was 2 days and 17 (43.6%) patients received combination therapy with multiple antifungal agents. Bronchoscopy with bronchoalveolar lavage was performed in 34 (87.2%) and of those a microbiologic diagnosis found in 5 (14.7%). Day 90 mortality was 56.0% (n=14). Survivors were more likely to have initiation of antifungal therapy within 7 days (96.0% vs 64.3%, p=0.016) and received liposomal amphotericin B as part of their initial therapy (72.0% vs 42.9%, p=0.009). Patients receiving corticosteroids or who failed to have neutrophil recovery tended to have higher mortality, but this did not achieve statistical significance. Combination therapy and receipt of granulocyte or granulocyte-macrophage colony-stimulating factors were not associated with improved day 90 mortality.

Conclusion

Early recognition and initiation of antifungal therapy in high-risk neutropenic patients with hematologic malignancy with IFI and initial therapeutic regimens including liposomal amphotericin B may be associated with improved outcomes.

Disclosures

All Authors: No reported disclosures
P-1046. Isavuconazonium Utilization in Pediatric Patients at a Free-Standing Children’s Hospital
Authors: Orbach Regina , Bee Jessica , Legaspi Jamie
Published: January 2025

Background

Isavuconazonium sulfate is a newer triazole antifungal used for the treatment of invasive aspergillosis and mucormycosis. In December 2023, the FDA expanded approval for isavuconazonium sulfate (Cresemba) to include pediatric patients 1 year and older. The most common adverse effect requiring monitoring is hepatotoxicity. Routine therapeutic drug monitoring is not recommended for most patients but may be considered if there is a concern for toxicity, therapeutic failure, or impaired drug absorption. With limited published data in pediatric patients, our aim is to evaluate the use of isavuconazonium at Children's Hospital Los Angeles (CHLA) and assess safety and tolerability in our patient population.

Methods

A retrospective chart review was performed to evaluate utilization of isavuconazonium from 01/01/2023 – 12/31/2023 at CHLA. Demographic data, Infectious Diseases consultation, indication for therapy, liver function before and during treatment, and serum drug level results were collected and analyzed.

Results

A total of 54 patient encounters included an isavuconazonium order during the review period. All study patients had a primary diagnosis of leukemia or stem cell transplant (SCT), the most common (45%) being Acute Lymphoblastic Leukemia (ALL). 3 patients had mildly elevated liver function tests (LFTs) at baseline, and 6 total patients developed grade 3 or 4 liver toxicity during therapy. The most common indication for treatment was empiric or definitive treatment of invasive fungal infection, with 15 (28%) and 20 (37%) patients, respectively. 19 patients (35%) received off-label prophylaxis for invasive fungal infection due to contraindications to alternative antifungal agents. 33 of 54 patients had at least one serum trough level measured at steady state. Although a therapeutic target range is not well established, 26 patients (79%) achieved levels within typical expected range of 1-5 mg/L. Of 3 patients with trough level < 1 mg/L, 2 were determined to be due to non-adherent to outpatient therapy.

Conclusion

Based on serum drug levels and LFT results collected for routine therapeutic monitoring, isavuconazonium appears well-tolerated for treatment or prophylaxis of invasive fungal infection in our immunocompromised pediatric population.

Disclosures

All Authors: No reported disclosures
P-1047. The Epidemiology of Sporotrichosis: Clinical Features, Risks Factors and Associated Mortality, a Global Research Network Analysis
Authors: Schapiro Samantha , Pulciano Nicholas , Galindo Julian , Martínez Andrés F Henao , Thompson George R , Chastain Daniel B
Published: January 2025

Background

Sporotrichosis is a fungal infection affecting thousands in South America, yet is uncommon globally, where it is not a reportable disease. This leads to a limited understanding of its epidemiology and clinical features.

The study aimed to identify and characterize the clinical features, geographic distribution, risk factors, and outcomes of sporotrichosis across a multicenter United States (US)-based network to improve diagnostic and treatment strategies.

Methods

The study used the TriNetX global research network database to identify patients with sporotrichosis defined by ICD-10-CM code B42. A manual chart review was conducted to verify the reliability of the code in 60 patients. Data collected included demographics, comorbidities, lab results, and outcomes. The primary outcome was mortality and hospitalization. Bivariate analysis was performed to compare survivors with non-survivors in one year.

Results

The study included 2,124 patients with sporotrichosis, with a manual chart diagnosis validation rate of 95%. The average age was 52, with 56% women and 40% Caucasian. Common comorbidities were neoplasms, diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Most cases were unspecified, but among those with a specified subtype, lymphatic was the most common (9.4%), followed by disseminated (1.1%). Itraconazole was the most common first-line treatment. The one-year mortality was 17% (Table 1). The Southeast had the most frequent cases in the US (Figure 1). Age, unmarried marital status, and location in south or international regions were significantly associated with mortality. Higher ferritin levels, lower hematocrit, and higher leukocyte count also indicated increased mortality (Table 2). There were 17 patients with both sporotrichosis and HIV; 82% were men with an average age of 56. The average CD4 count was 65.5, with a one-year mortality of 17.6% (Table 3).

Conclusion

Patients with sporotrichosis had low rates of extracutaneous disease. Age, unmarried marital status, geographic location, and specific comorbidities such as neoplasms, DM, and COPD are significant factors affecting sporotrichosis survival. Despite their compromised immune status, patients with HIV did not have worse outcomes than the general sporotrichosis population.

Disclosures

George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant
389. Trends in HIV-Related Mortality Among Reproductive-Aged Women in the United States
Authors: Ali Shah M Danial , Aslam Sadaf , Rybolt Lauren E , Fatima Abeer , Sherbuk Jacqueline E , Somboonwit Charurut
Published: January 2025

Background

Despite advancements in HIV treatment, there remains a significant gap in understanding mortality rates among reproductive-aged women with HIV in the United States. To enhance evidence-based interventions, this study aims to delineate mortality trends from 1999-2020, focusing on demographic characteristics such as age, race, and geographic regions.

HIV-related AAMRs per 100,000 individuals stratified by race in women aged 15-44 in the United States, 1999 to 2020.

Methods

This study involved a retrospective analysis using the CDC WONDER database, extracting data via ICD-10 codes B20-B24 to identify HIV-related deaths among women aged 15-44 from 1999 to 2020. We analyzed demographic disparities in HIV mortality rates over time based on age, ethnicity, and geographic regions using systematic database analysis. Results are presented as age-adjusted mortality rate (AAMR) and 95% confidence interval (CI). These were calculated by standardizing HIV-related deaths in the United States in 2000.

HIV-related AAMRs per 100,000 individuals stratified by state in in the United States among women aged 15-44 from 1999 to 2020.

Results

Between 1999 and 2020, a total of 29,358 women aged 15-44 died from HIV in the US (AAMR = 2.2 per 100,000; 95%CI: 2.2-2.2). The crude mortality rate declined from 4.2 in 1999 to 2.1 in 2020. The overall decline in mortality rates masked disparities: Non-Hispanic Black women experienced the highest AAMR (11.3), while Hispanics, though initially higher, saw the most substantial decrease in mortality rates (1.4). Geographical analysis revealed the South as the most affected region (3.5), accounting for 58.3% of deaths, with urban areas presenting higher mortality rates than rural ones (2.4 and 1.4). Notably, older age groups (35-44) accounted for the majority of deaths (67.1%)

HIV-related AAMRs per 100,000 individuals among women aged 15-44 from 1999 to 2020 in the United States census regions. *=significant at p < 0.05; confidence interval does not include zero

Conclusion

HIV-related mortality among reproductive-aged women decreased nationally from 1999 to 2020, yet disparities persist. Our analysis emphasizes the disproportionate impact of HIV-related deaths on non-Hispanic Black women and those residing in the Southern United States, suggesting the need for region and population-specific public health interventions. This highlights the need to improve access to care, particularly in urban areas, and target age-specific prevention programs to further reduce mortality rates. Improving timely diagnosis and addressing the stigma surrounding HIV among women is vital to reduce mortality in this demographic.

HIV-related crude mortality percentage stratified by different variables in women aged 15-44 in the United States, 1999 to 2020

Disclosures

All Authors: No reported disclosures
P-1057. Leveraging A Global-Scale Atlas of Phage Host Interactions to Discover Novel Precision Antimicrobials
Authors: Bryson Sam , Auch Benjamin , Grove Jonas , Nelson Bradley J , Glidden Demi , Reister Emily , Liachko Ivan
Published: January 2025

Background

A growing global antimicrobial resistance (AMR) crisis fueled by the overuse of traditional antibiotics has created an urgent need not only for new antimicrobials, but entirely new approaches for sustained therapeutic development against existing and emerging pathogens. Endolysins (lysins) have demonstrated both efficacy and safety as precision antimicrobials that overcome the resistance problem posed by most other antibiotic modalities. However, due to the difficulty of identifying new sources of lysins, development has been slow.

Methods

We have adapted a unique genomic technology, proximity ligation sequencing, to harness the vast genetic diversity of microbial viruses (phages) to discover large-numbers of protein-based interventions against microbes. Proximity-guided metagenomics allows us to pinpoint the microbial targets of phages in situ, recovering the genomes of both microbe and phage without culturing or isolation of either party. Inherently, each lytic phage genome encodes one or more more proteins (endolysins) which can lyse their host cell. Each of these proteins represents a powerful tool in the targeted destruction of a selected organism, and because we know which species of microbe each phage infects, we can identify candidate lysins from proximity-guided metagenomic data alone.

Results

As part of our global-scale metagenomics project, we used our ProxiMeta platform to recover the target-resolved genomes of hundreds of thousands of phages across the tree of life. We will share published and unpublished work describing our discovery and evaluation of these lysins, and their applications in selectively killing microbes involved in human disease.

Conclusion

Phage genomes from metagenomic databases are a rich source of antimicrobial proteins that can be developed into novel antimicrobial agents.

Disclosures

All Authors: No reported disclosures
P-1073. Developing Vaccines and Antibodies Targeting Conserved Peptidoglycan, Lipoteichoic Acid, and Lipopolysaccharide Epitopes to Combat Antimicrobial Resistance
Authors: Sei Clara J , Rikhi Nimisha , Kroscher Kellie , Schuman Richard F , Muema Kevin , Assiaw-Dufu Aba , Fischer Gerald W
Published: January 2025

Background

Antimicrobial resistance (AMR) poses a significant global health threat, driving the urgent need for non-antibiotic therapies such as vaccines and monoclonal antibodies (mAbs). Targeting conserved epitopes on gram-positive and gram-negative bacteria, including mycobacteria will be important for developing strategies against AMR. Key epitopes, including Peptidoglycan (PGN), Lipoteichoic acid (LTA), and Lipopolysaccharide (LPS) are crucial in this context. In this study, we illustrate the efficacy of a mAb directed against ultrapure PGN from Staphylococcus aureus (SA), alongside the capabilities of polyclonal serum antibodies induced by a multi-epitope composite peptide vaccine comprised of PGN, LTA, and LPS epitopes.

Methods

MAb MD11 was produced from a mouse immunized subcutaneously with ultrapure PGN from SA and the mAb specificity identified using ultrapure PGN and a synthetic PGN peptide in a competitive inhibition assay. Additionally, polyclonal serum antibodies were derived from ICR mice immunized subcutaneously on days 0, 21, and 35 with 20 µg of multi-epitope composite peptide vaccine LPS.PGN.LTA05, formulated with AddaVax™ adjuvant. IgG1 titers to the immunogens and whole bacteria: SA, Staphylococcus epidermidis, Mycobacterium smegmatis, Escherichia coli, B. subtilis, Grp. B Streptococcus and killed Mycobacterium tuberculosis (MTB) were analyzed by ELISA.

Results

MAb MD11 recognized and opsonized various gram-positive bacteria, including mycobacteria. PGN peptide competitively inhibited binding of MD11 to Ultrapure PGN, indicating specificity of MD11 to PGN epitope. Robust and broad polyclonal serum IgG1 antibodies recognizing both gram-positive and gram-negative bacteria, including mycobacteria were generated by the multi-epitope composite peptide vaccine.

Conclusion

Anti-PGN mAb MD11 was broadly reactive to gram-positive bacteria. Polyclonal serum antibodies showed broad reactivity across both gram-positive and gram-negative bacteria, including mycobacteria. Developing vaccines and antibodies that target conserved bacterial epitopes may provide important strategies for prevention and treatment of bacterial infections, particularly for immunocompromised individuals, and could offer a useful approach to combat AMR.

Disclosures

All Authors: No reported disclosures
P-1077. Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam (C/T) Real-world Analysis (SPECTRA): Clinical Outcomes and Treatment Patterns from Mexico
Authors: Saldivar Ines , Ayala Pedro Martínez , Ortiz Adrian Camacho , Castañeda-Méndez Paulo , Morfin-Otero Rayo , Zhou Yanbing , Polis Thales , Yucel Emre
Published: January 2025

Background

Reported are results of SPECTRA data from Mexico

Methods

SPECTRA (n=617) is a 7-country multicentre retrospective observational study, including hospitalized adult patients (≥18 years) treated with C/T for ≥48 hours. Medical records were reviewed for 30 days after the last dose of C/T or until death. Reported are clinical outcomes and treatment patterns in Mexico.Table 2.All-cause in-hospital mortality (ACHM) in the Mexico cohort

Results

Mean age of patients (n=59) is 55.2 years, and 47.5% were female. Common comorbidities were diabetes mellitus (DM) uncomplicated (18.6%) and DM with end organ damage (3.4%), transplantation (16.9%), heart disease (16.9%), chronic kidney disease (11.9%), chronic pulmonary disease (10.2%), acute kidney injury (10.2%), and end-stage renal disease (3.4%). From positive cultures (n=32) were found 21 multi-drug resistant (MDR) Pseudomonas aeruginosa (PsA) (65.6%) and 4 MDR Enterbacterecea (12.5%). C/T was used to treat pneumonia (30/59, 50.8%), complicated intra-abdominal infection (9/59,15.3%), complicated urinary tract infection (8/59, 13.6%), bone and joint infection (8/59, 13.6%), and sepsis (8/59, 13.6%). Mean time from the index hospitalization admission to C/T initiation is 16.0 days. Mean time from the first microbiology (MB) sample for the index infection to C/T initiation is 1.9 days. C/T treatment duration was median 8.0 days (Q1:Q3; 5, 11). Doses included 54.2% 1.5g/Q8h; 39.0% 3g/Q8h; 5.1% 750mg/Q8h; 1.7% 1g/Q8h. C/T rank of initiations: first-line (49.2%), second-line (42.4%), third-line (6.8%), fourth-line (0), fifth-line (1.7%), sixth+line (0). Of all the cases, empiric therapy accounted for (37/59) 62.7%, definitive therapy in (17/59) 28.8%, and undetermined (5/59) (8.5%).

Clinical success rate for treating the index infection with C/T is 79.7% of patients (Table 1). All-Cause-Hospital-Mortality (ACHM) is 16.9%. Median time from index date to death is 12.0 days (Table 2). ICU admission is reported in 42.4% of cases, with a median ICU length of stay at 20.0 days (Table 3).Table 3.ICU admission and LOS during the index hospitalisation from the Mexico† ICU LOS if ICU admission was related to index infection.CI, confidence interval; ICU, intensive care unit; LOS, length of stay; SD, standard deviation.

Conclusion

Results show real-world effectiveness of C/T in Mexico, more research is warranted.

Disclosures

Yanbing Zhou, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company) Thales Polis, MD, MSD: Stocks/Bonds (Public Company) Emre Yucel, PhD, Merck: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|Merck: Stocks/Bonds (Public Company)
P-1086. COT-832, a Novel Polyene Macrolide Antifungal (I): In Vitro Antifungal Activity against Candida, Aspergillus, and Mucor, etc., Hemolytic Activity, and Cytotoxicity
Authors: Maki Hideki , Nishiyama Yuri , Ohara Takafumi , Sugimoto Hideki
Published: January 2025

Background

A novel polyene macrolide antifungal, COT-832 was created by SHIONOGI through structurally modifying Amphotericin B(AmB). Invasive fungal infections are commonly treated with antifungal drugs such as azoles, polyenes, and echinocandins; however, their efficacy is limited and mortality rates remain high. Therefore, the development of more effective and safer antifungal drugs is needed. AmB is available in formulations such as Fungizone (FGZ), which utilizes a deoxycholic acid formulation, and AmBisome (L-AMB), which employs a liposome formulation. While these polyene antifungals exhibit activity against a wide range of fungal species, their usage is often discontinued due to the nephrotoxicity associated with AmB itself. This study aimed to evaluate the antifungal activity, hemolytic activity, and cytotoxicity of COT-832 in vitro.

Methods

Antifungal activity was assessed using the CLSI method on clinical isolates from Japan (2012-2016). Hemolysis activity was measured after applying compounds to 4% sheep red blood cells for 24 hours. Cytotoxicity was evaluated by applying compounds to HepG2 cells for 2 hours and measuring lactate dehydrogenase (LDH) levels in the supernatant with Cytotox96 assay for calculating cell survival rate.

Results

Antifungal activity: COT-832 exhibited MIC90 of 0.5-2 µg/mL against Aspergillus and Candida, matching AmB's MIC. It also showed efficacy against azole-resistant A. fumigatus and echinocandin-resistant C. glabrata. COT-832's MIC90 for Cryptococcus was 0.5 µg/mL, surpassing AmB. Similar MICs were observed for rare molds.

Hemolytic activity: AmB caused hemolysis from 0.625 µg/mL, reaching 80% at 2.5 µg/mL. COT-832 displayed an 8% hemolysis rate at 2.5 µg/mL.

Cytotoxicity: AmB reduced cell count from 2 µg/mL, while no noticeable decrease occurred with COT-832 up to 72 µg/mL.

Conclusion

COT-832 exhibits comparable antifungal activity to AmB while demonstrating reduced toxicity against various cells, up to a tenfold decrease compared to AmB. These findings suggest that COT-832 has potential for development as a safer polyene macrolide antifungal drug, offering potent antifungal activity across a wide range of fungal species.

Disclosures

Hideki Maki, PhD, Shionogi & Co., Ltd.: employee|Shionogi & Co., Ltd.: employee Yuri Nishiyama, MS, Shionogi & Co., Ltd.: employee Takafumi Ohara, n/a, Shionogi & Co., Ltd.: employee Hideki Sugimoto, n/a, Shionogi & Co., Ltd.: employee
P-1089. Pharmacokinetics of Rifaquizinone in Rats and Dogs Following Intra-Articular Administration
Authors: Wang Huan , Cheng Qin , Xiong Haiwei , 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. The current studies investigate the pharmacokinetics (PK) of RFQ following intra-articular (IA) administration to rats and dogs.

Methods

In the first study, 18 male rats were assigned into Group 1-3 and received a single dose of 10 mg/kg RFQ formulated in 5% (w/v) glucose, saline, or 4% (w/v) Solutol HS15 in 5% (w/v) glucose, respectively. In the second study, six (3/sex) beagle dogs received a single dose of 3 mg/kg RFQ in 5% (w/v) glucose on the left leg and an equal volume of vehicle on the right leg. Blood and synovial fluid samples were collected and concentrations of RFQ were determined by liquid chromatography tandem mass spectrometry.

Results

Following a single dose of IA administration of 10 mg/kg RFQ in rats, the maximum plasma concentrations (Cmax) were 289, 130 and 139 ng/mL in Group 1, Group 2 and Group 3, respectively. The mean synovial fluid concentrations of RFQ reached 76,844, 371,887 and 367,912 ng/mL at 24 hour after dosing for Group 1, Group 2, and Group 3, respectively. Following a single dose of IA administration of 3 mg/kg of RFQ in dogs, the Cmax in plasma was 736 ng/mL, while the mean synovial fluids concentrations at 12 and 36 hours post dosing were 77,300 and 2,240 ng/mL, respectively. The synovial fluid concentration were 38.7 and 1.12 fold higher than the minimum biofilm bactericidal concentration inhibit 90% bacterial growth (MBBC90) for S. aureus (MBBC90 = 2,000 ng/mL) and 309 and 8.96 fold higher than the MBBC90 for S. epidermidis (MBBC90 = 250 ng/mL).

Conclusion

The 5% (w/v) glucose appeared to be the best vehicle for IA administration of RFQ based on the tolerability and elimination profile. RFQ reached a high local synovial fluid concentration significantly higher than the MBBC90 for S. aureus and S. epidermidis for a prolonged period of time, while maintaining a low systemic exposure. The current studies supporting further evaluation of RFQ for the treatment of PJI via IA administration.

Disclosures

Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Qin Cheng, Master, TenNor Therapeutics (Suzhou) Ltd: Employee Haiwei Xiong, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee
P-1097. Efficacy of Rifaquizinone in a Murine Model of Prosthetic Joint Infection (PJI) with Fluoroquinolone-Sensitive and -Resistant Staphylococcus aureus
Authors: Pulse Mark E , Nguyen Phung , Valtierra David , Peterson Kelly , Ma Zhenkun , Wang Huan , Weiss William J
Published: January 2025

Background

Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or acquired resistance to commonly used antibiotics and those associated with medical devices. RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. Current studies sought to evaluate the therapeutic efficacy of RFQ following intraperitoneal (IP) administration for 7- to14-day treatment in a murine model of S. aureus prosthetic joint infection (PJI).

Methods

K-wire was implanted in right hindlimb femurs of C57/BL6 mice followed by infection with 6.5-6.9 log10 CFU of a fluoroquinolone-sensitive (UNT005-4) or -resistant (UNT002-3) S. aureus strain. Doses of RFQ, ciprofloxacin, vancomycin, and vehicle were IP administered BID for 7 or 14 consecutive days starting 7 or 21 days after infection. Infected wires and femurs were collected and processed for CFU counts from untreated groups at the start of treatment and treated/vehicle groups within 18 hours of the final administered dose.

Results

In the 7 day UNT005-4 infection study, mean wire and femur counts for the infection group were 4.77 log10 CFU and 7.89 log10 CFU on Day 7 and for vehicle treatment were 5.02 log10 CFU and 6.83 log10 CFU on Day 14. Comparatively, RFQ at doses of 10, 25, and 62.5 mg/kg for 7 days treatment significantly reduced mean wire and femur counts by > 2.40 and > 1.60 log10 CFU. In the 21 day UNT005-4 infection study, compared to the infection and vehicle treatment, the same doses of RFQ administered for 14 days significantly reduced mean counts by >1.02 log10 CFU for wires and > 0.88 log10 CFU for femurs. In the 21 day UNT002-3 infection study, RFQ administered for 14 days significantly reduced mean counts by > 1.50 log10 CFU for wire and > 0.9 log10 CFU for femur. As expected, reduction in mean counts following 7 or 14 days of ciprofloxacin and vancomycin treatments were less than RFQ.

Conclusion

RFQ IP administered doses significantly reduced wire- and femur-associated counts for both S. aureus strains, and despite UNT002-3 resistant to ciprofloxacin treatment, the RFQ remained efficacious in the murine PJI model.

Disclosures

Mark E Pulse, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Phung Nguyen, BS, TenNor Therapeutics (Suzhou) Ltd: Investigator David Valtierra, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Kelly Peterson, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee William J Weiss, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator
P-1109. A phase 2, randomized, double-blind study of ibezapolstat compared with vancomycin for the treatment of Clostridioides difficile infection: clinical and microbiome evaluation
Authors: Eubank Taryn A , Jahangir Alam M , Begum Khurshida , McPherson Jacob , Jo Jinhee , Silverman Michael , Garey Kevin W
Published: January 2025

Background

Ibezapolstat (IBZ) is Gram-positive selective spectrum antibiotic that inhibits the bacterial DNA polymerase IIIC currently in clinical trial development for the treatment of C. difficile infection (CDI) in adults. In the open-label, non-comparative, phase 2a study, 10 of 10 IBZ-treated CDI patients experienced clinical cure. The purpose of the phase 2b CDI study was to assess the safety, efficacy, and microbiome change of IBZ versus vancomycin (VAN).

Methods

Phase 2b (ClinicalTrials.gov, number NCT04247542) was a randomized, double-blind, active-comparator study. Participants with signs and symptoms of CDI and a positive enzyme immunoassay toxin test result were recruited from 12 centers in the USA and randomly assigned (1:1) to receive oral IBZ 450 mg every 12 h or oral VAN 125 mg every 6 h for 10 days. Stool was collected daily for microbiome evaluations. The primary endpoints were clinical cure at the end of therapy visit and safety. Secondary endpoints included microbiologic and microbiome evaluations.

Results

Thirty patients were recruited and were assessed in the per protocol analysis. (IBZ: n=16; VAN n=14). Fifteen of 16 (93.8%) patients given IBZ had a clinical cure versus 14 of 14 (100%) patients given VAN. IBZ and VAN were well tolerated with no serious drug-related events. C. difficile was eradicated from all stool samples after day 3 of treatment for IBZ-treated patients while three VAN-treated patients had C. difficile growth after day 3. IBZ demonstrated consistent preservation of key Bacillota species while significant decreases were observed in VAN-treated patients. CDI recurrence occurred in two patients given VAN and no patients given IBZ.

Conclusion

In the phase 2b study, IBZ had a clinically comparable cure rate and safety profile to oral vancomycin. Favorable microbiologic and microbiome findings were observed with IBZ-treated patients along with a lower rate of CDI recurrence. These results warrant further development in phase 3 trials.

Disclosures

Michael Silverman, MD, Acurx: Advisor/Consultant Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support
P-1121. Unconventional Selection Pressures for Resistance in Immunocompromised Gut Resistomes: A Multicenter Observational Study of Pediatric Hematopoietic Stem Cell Transplant Recipients
Authors: Duggar Marygrace , Jia Qidong , Sun Yilun , Tang Li , Margolis Ellie
Published: January 2025

Background

Increased antibiotic exposure contributes to antibiotic resistance in immunocompromised hosts. Studying how antibiotic courses alter resistance development in their gut community, a common source of bloodstream infections, helps identify treatments posing risk for colonization with Multidrug Resistant Organisms (MDROs).

Methods

Stool samples were collected from 163 children pre, day +30, and post-neutrophil engraftment during HSCT, approved by IRBs at St. Jude Children’s Research Hospital and University of Bologna. DNA extracted from these samples underwent Illumina metagenome sequencing, yielding 25 million reads/sample. Antibiotic resistance genes (ARGs) were identified using MEGARes (v 3.0). The children, with median age 8.4, mainly underwent HSCT for Acute Myeloid Leukemia (60%), with majority receiving reduced intensity conditioning (66%). They received multiple antibiotic doses (median 42 daily doses) for fever and neutropenia, infection treatment, and prophylaxis (trimethoprim-sulfamethoxazole at all institutions; fluoroquinolones exclusively at St Jude). ARG abundance was adjusted for sequencing depth and gene length, and changes over time were compared based on antibiotic exposure using linear mixed models.

Results

In pediatric HSCT recipients, the resistome, collection of antibiotic resistance genes in the stool microbial community, differed from healthy children and those with leukemia (fig 1). Surprisingly, levels of antibiotic resistance genes for commonly used antibiotics like Glycopeptides, Pseudomonal Cephalosporins, Aminoglycosides and Fluoroquinolones didn’t increase in children treated with those specific antibiotics. Increases in MDRO related genes (e.g. multidrug efflux pumps, ESBL, vanA) were linked to exposure to antibiotics with anaerobic activity.

Conclusion

Commonly used antibiotics may minimally affect pediatric HSCT patient’s resistomes due to limited gut penetration or prior exposures saturating selection. Other factors like turnover, radiation, inflammation, or conditioning may drive ARG selection. Antibiotics with anaerobic activity link to MDRO related genes suggest colonization resistance may hinder MDRO colonization, warranting increased stewardship.

Disclosures

Ellie Margolis, MD PhD, ICLR: Stocks/Bonds (Private Company)
P-1125. Impact of a Persuasive Antimicrobial Stewardship Program on Antibiotic Consumption and Mortality in a Neonatal Unit: A Before-and-After Study
Authors: Londono-Ruiz Juan Pablo , Betancourt Santiago Loaiza , Rodriguez-Acosta Diana Lucia , Rodriguez Viviana
Published: January 2025

Background

Antimicrobial Stewardship Programs (ASPs) have established themselves as the most effective strategy for reducing the consumption of unnecessary antibiotics, and thereby minimizing the emergence of antimicrobial resistance and adverse effects. However, implementing ASPs in neonatal units presents unique challenges due to their high use of antibiotics and the limited clinical tools available to diagnose infections. The aim of this study is to present the results of a before-and-after study that evaluated the impact of implementing an ASP with persuasive strategies on antibiotic consumption in a neonatal unit.

Methods

The study was conducted in a neonatal unit of a general hospital that attends approximately 200-400 deliveries per month and has a high-risk obstetric program. The ASP was initiated with a weekly round of antibiotic control and an analysis and feedback strategy. Weekly education and training sessions were conducted for all staff, and the pediatric infectious diseases service was made available for permanent consultation. Local guidelines were developed and shared with all unit personnel, and the Days of Therapy (DOT) of the main antibiotics used was measured. Data analysis was performed using the R program.

DOT and Mortality in Pre-ASP and Post-ASP periods

Results

DOT measurements of ampicillin, gentamicin, amikacin, piperacillin-tazobactam, cefepime, and vancomycin were collected since 2021. In November 2022, a spot study was conducted to identify the microbiology of the neonatal unit, and the ASP was implemented. An analysis and feedback strategy were used, with additional support from a weekly round that included neonatologists, pediatricians, therapists, and nursing staff. The monthly DOT are shown in Figure 1. The average DDDs were compared between the period before the ASP and the period after, revealing a significant decrease in all antibiotics except for vancomycin (Table 1). A mortality rate of 2.08 per 100 live births was documented in the Pre-ASP period, which decreased to 1.2 per 100 live births in the post-ASP period.

Conclusion

Antibiotic stewardship programs that implement persuasive measures can be effective in reducing the consumption of most antibiotics in a neonatal unit. Mortality did not increase despite the reduced use of antibiotics.

Disclosures

All Authors: No reported disclosures
P-1130. Association Between Procalcitonin, CRP Values and Antibiotic Use in Children with Community-Acquired Pneumonia
Authors: Montenegro Liliana Arriola , Mulekar Madhuri S , Hassouneh Linda
Published: January 2025

Background

Procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers used to help identify bacterial etiologies of community-acquired pneumonia (CAP) as it is often challenging to differentiate between viral and bacterial causes. This study evaluated the association between PCT, CRP values, and antibiotic initiation in children with CAP.

Methods

This single-center, retrospective study evaluated patients aged 6 weeks to 19 years who presented with acute signs or symptoms of lower respiratory tract illness from December 1 2022 to December 31, 2023. Enrolled were patients with PCT and CRP values obtained within the first 24 hours of their hospital visit. The primary outcome was the initiation of antibiotics within the first 36 hours of the encounter. Patients with tracheostomy, prior antibiotic use, aspiration, or hospital-acquired pneumonia were excluded. PCT and CRP were categorized into 4 groups correlating to values suggesting very unlikely, unlikely, likely, and very likely bacterial infection. Bivariate and logistic regression analyses were conducted.

Patients outcomes (admission to PICU, pleural effusion and need for intubation) by Procalcitonin levels

No association was seen between patient outcomes and procalcitonin levels.

Results

The study included 193 patients, 83% of whom received antibiotics. Among these, 11% had a PCT < 0.1 ng/ml and 8% had a CRP < 0.3 mg/dl. Third-generation cephalosporins (3GC) were the most commonly used antibiotic (n=139, 72%). PCT and CRP values were strongly associated with initiation of antibiotics (p< 0.0001). CRP >10 mg/dl had a 14.8% increase in odds of receiving antibiotics (95% confidence interval [CI]: 2.8, 78.2), and PCT >0.5 ng/mL had a 6.9% increase in odds (95%CI: 2.3, 21.2) compared to the reference category (PCT < 0.3 ng/mL and CRP < 0.3 mg/dL respectively). A CRP of ≥10mg/dL and PCT of >0.5 ng/mL were associated with using 3GC and methicillin-resistant Staphylococcus aureus (MRSA) coverage. Days of hospitalization, pleural effusion, intubation, and PICU admission were not associated with PCT and CRP values.

Conclusion

Most subjects received antibiotics including those with normal PCT and CRP levels, suggesting a possible overuse of antibiotics. Higher levels of PCT and CRP were associated with antibiotic initiation and usage of broad-spectrum antibiotics, identifying opportunities for antibiotic stewardship.

Disclosures

All Authors: No reported disclosures
P-1144. Low prevalence of neonatal sepsis due to Streptococcus agalactiae in two large Mexican NICUs: multicenter retrospective study from 2021-2023
Authors: Ballesteros-Suarez Ana , Garza-Castro Abraham P , Concha-Mora Lindsay A , Prieto-Baca Ericka Paulina , Tamez-Rivera Oscar , Salazar-Alejo Misael
Published: January 2025

Background

Group B Streptococcus (GBS), or S. agalactiae, is reported as a leading cause of neonatal sepsis in several regions including the United States. Although in recent years its incidence has shown a steady decline, current treatment guidelines still consider it a predominant cause of neonatal sepsis. Its prevalence varies according to geographical and racial factors; however, information regarding the epidemiology and clinical presentation of neonatal GBS infection in Mexico is scarce.

Methods

Retrospective multicenter study conducted in the NICUs of the two pediatric reference hospitals in NL, Mexico. Data of all newborns ≤28 days (d) diagnosed with blood culture-proven GBS infection from 2021-2023 were collected. Maternal premature rupture of membranes (PROM) was defined as >12h. GBS infection was classified as early (< 7 d) and late-onset (≥7 d). LBWIs were defined as newborns < 2500 g and very LBWI (VLBWI) as < 1500 g at birth, respectively. Clinical scenarios were classified as sepsis, pneumonia and meningitis. Sepsis was classified as early (≤3 d) and late-onset ( >3 d). Descriptive statistical analyses were performed to determine frequencies.

Results

A total of 928 positive blood cultures were included. 28 blood cultures (3%) from 27 patients were positive for GBS. Maternal PROM was documented in 11.1%. Most patients were term infants (77%) and 92.6% of the cases were early-onset. The most common presentation was sepsis (92.6%). One patient (3.7%) had pneumonia and one (3.7%) had meningitis due to GBS. Low mortality was documented (3.7%). Table 1 shows clinical characteristics of patients with GBS infection. As expected, all isolates were susceptible to Ampicillin.

Conclusion

We report a low prevalence of culture-proven GBS infection (3%) in two large Mexican NICUs during the studied period. This is consistent with previous single-center reports from Mexico, which date back to more than two decades. Although the international epidemiology and treatment guidelines consider GBS a predominant cause of neonatal sepsis, its frequency in Mexico remains low. The vast majority of cases were early-onset infections, and the most common clinical presentation was sepsis, which is consistent with global epidemiology.

Disclosures

All Authors: No reported disclosures
P-1148. Invasive Infections by Carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa in Children
Authors: Cazes Claudia Inés I , Biondi Estefania , Lanfranchi Romina , Cancellara Aldo , Procopio Adriana , Ordoñez Carolina , Ezcurra Gustavo Cesar , Aró Carolina , Juarez Ximena S , Flores Ezequiel , Cames Valeria , Dondoglio Patricia , Pereda Rosana , Granchetti Hugo , Pezzaniti Antonella , Satragno Daniela , Vazquez Miryam , López Eduardo L
Published: January 2025

Background

Enterobacterales and Pseudomonas aeruginosa cause invasive infections and their spread of antimicrobial resistance is of great concern in the worldwide scientific community. Carbapenemases represent the main mechanism of resistance in Enterobacterales and can spread horizontally through mobile genetic elements. Clinical evidence suggests that mortality would be related to inadequate initial empirical treatment.

Methods

A prospective observational study was carried out in three tertiary care pediatric hospitals in Argentina, since 12/1/2021 to 11/30/2022, including children between 0 to 18 years of age with a positive culture for carbapenemase-producing Enterobacterales or P. aeruginosa isolated from a sterile site and/or tracheal aspirate with pulmonary radiological confirmation.

Results

We enrolled 29 patients, 62% male. Median age: 25 months (IQR 5-127). Median length of hospitalization: 44 days (IQR 17-91). Comorbidities: 93%, oncohematological disease: 40%; 62% (18/29) were admitted to Intensive Care Unit. The most frequent isolation was Klebsiella pneumoniae: 62% (18/29), Escherichia coli 17% (5/29), Enterobacter cloacae 10% (3/29), Serratia marcescens 7% (2/29), P. aeruginosa 7% (2/29). Bacteremia: 55% (16/29). Most frequent site of infection: urinary tract 44.8%. Metallobetalactamase (MBL) was detected in 48% (14/29), KPC: 34% (10/29), OXA: 14% (4/29). Initial empirical treatment: meropenem 53% (16/29). Adjustment of initial empirical treatment at 48 hours: 79% (23/29) according to cultures and antibiogram. Ceftazidime/avibactam: 48.2%; aztreonam combined in MBL strains. Extended infusion meropenem: 24% (7/29) if MIC ≤ 8 ug/ml. Overall mortality: 20.6%, in 6.8% it was related to infection.

Conclusion

In recent years we have seen an increase in antimicrobial resistance. Metallobetalactamases were the most frequently detected in patients hospitalized in critical areas. Resistance data in Argentina showed K. pneumoniae as one of the most prevalent bacteria in multidrug-resistant infections. Carbapenemes in high doses and extended infusions plus other antibiotics were useful to treat strains with low MIC values. Ceftazidime/avibactam was a good option for KPC and some OXA infections. Aztreonam in combined use was indicated for MBL strains.

Disclosures

All Authors: No reported disclosures
P-1153. Characteristics of Invasive Group A Streptococcal Infections (iGAS) in Children during the COVID-19 Pandemic
Authors: Granberry Emma , Pinninti Swetha , Boppana Suresh
Published: January 2025

Background

Group A Streptococcus (GAS)/Streptococcus pyogenes is the most common cause of bacterial pharyngitis in all age groups and can also cause invasive GAS (iGAS) infections such as pneumonia, toxic shock syndrome, necrotizing fasciitis, and osteoarticular infections ± bacteremia. In the fall of 2022, the Centers for Disease Control (CDC) issued a health advisory documenting an increase in pediatric iGAS, following discontinuation of respiratory mitigation strategies (masking) during the COVID-19 pandemic. The primary objective of this study is to compare the incidence and severity of iGAS infections before and during the COVID-19 pandemic.Figure 1:Incidence of Pediatric iGAS at Children’s of Alabama

Methods

Isolation of GAS from a sterile site by culture or molecular methods was considered as iGAS. After review of electronic medical records (EMR), we identified 50 children < 18 years of age who were admitted to Children’s of Alabama (COA) between 2017 and the first quarter of 2023 with iGAS were identified. The cohort was divided into 2 groups: 1) pre-COVID-19 (Jan 2017 – Feb 2020) and 2) COVID-19 (March 2020 – Feb 2023). Demographic, clinical, and laboratory characteristics were abstracted and compared between the groups. Continuous variables were compared by the Mann-Whitney test, and Chi-square/Fisher’s exact test was used to compare categorical variables. P value < 0.05 was considered statistically significant.Table 1:Comparison of Laboratory Parameters between Groups

Results

Incidence of iGAS infection at COA plummeted during the COVID-19 pandemic from a peak of 16 cases in 2019 to 3 in 2021, followed by an increase in incidence but still lower than the pre-pandemic levels after the discontinuation of respiratory mitigation strategies (Figure 1). No significant difference between the two groups was observed for severity of infection (p = 1) and laboratory markers (Table 1).

Conclusion

In this single center, retrospective study of pediatric iGAS infections, the number of children with iGAS infections decreased dramatically in 2020 and 2021 with an increase in 2022. We did not observe the increase in nationwide iGAS cases reported by CDC. Also, we did not observe significant differences in the severity of iGAS infections despite the rise in cases after the discontinuation of pandemic-era masking mandates.

Disclosures

Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support