bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &gt; 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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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
P-1142. Evaluating Ambulatory Antibiotic Prescribing for Respiratory Infections at a Pediatric Institution
Authors: Yu Diana , Vaz Louise E , Nolt Dawn 
Published: January 2025

Abstract

Background
Over 85% of antibiotic prescribing occurs in outpatient settings such as emergency departments (ED), urgent care centers (UCC), and primary care clinics (PCC); almost half of antibiotics are prescribed for respiratory infections (RI). Given the rise of telehealth visits (TH) in both UCC and PCC settings in the past several years, this study examines the effect of location sites on antibiotic prescribing for RI at our institution.

Methods
Single-center, retrospective cohort study in Portland, Oregon, USA. Patients &lt; = 20 years of age seen in the ED, UCC, and PC settings between 1/1/2019-12/31/2024, were included. Electronic data included age, race, ethnicity, location and encounter type, payor status, visit ICD-10 codes, and antibiotic prescription details. Multivariate logistical regression determined the effect of patient factors on antimicrobial prescribing.

Results
A total of 157,499 ambulatory encounters were included of which 24,236 were respiratory ICD10 code-related visits. Respiratory visit rates were not significantly different between non-Hispanic White and Hispanic/non-White children or by age group. RI were categorized as viral (57.7%), possible bacterial (37.6%), or co-infection (4.7%); antibiotics were prescribed 5.3%, 60.4%, and 62.8% of visits respectively. The rate of antibiotic prescribing for viral and possible bacterial RI was not different between non-Hispanic White and Hispanic/non-White children or between payor status. For viral RI, PCC and UCC settings were more likely to prescribe antibiotics compared to the ED (OR 1.4 and OR 2.36, respectively). Furthermore, PCC and UCC were less likely to prescribe narrow-spectrum antibiotics for possible bacterial RI compared to the ED (OR 0.84 and OR 0.79, respectively), including TH PCC and TH UCC visits (OR 0.29 and OR 0.56, respectively).

Conclusion
Pediatric patients with RI can receive ambulatory care through multiple settings. PCC TH (although a small percentage of all RI visits) shows the highest use of antibiotics for viral RI and the least narrow spectrum antibiotic prescribing for presumed bacterial RI. Efforts to reduce antibiotic use in viral RI should focus on non-ED settings, including TH. Strategies to encourage use of narrow-spectrum activity agents for RI should be shared with all departments.

Disclosures
All Authors: No reported disclosures