bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1078. Gentamicin-releasing polydopamine catheter coating to prevent urinary catheter-related infections
Authors: Su Gillian , Karp Hannah , Schulz Michael , Rao Jayasimha , Nowak Elizabeth , Sriranganathan Nammalwar 
Published: January 2025

Abstract

Background
Catheter-associated urinary infections (CAUTIs) are among the most common healthcare-associated infections in the United States. The risk of CAUTI corresponds to the duration of catheterization; prolonged catheter uses impacts patient morbidity, mortality, and healthcare costs. Pseudomonas aeruginosa is a leading cause of CAUTI and is particularly adept at forming surface-associated biofilms that are difficult to treat. In the present study, we developed a catheter coating using polydopamine (PD) to embed gentamicin on the surface.
Bacterial Viability of PAO1 when exposed to PD-gentamicin coating

Colony-forming unit (CFU) count of PAO1 exposed to concentration series of PD-only and PD-Gent well plate coating.

Methods
Coating synthesis: PD-antibacterial coating was synthesized using dopamine hydrochloride salt and antibiotic drugs (i.e., gentamicin) in an alkaline buffer in the presence of polyvinyl chloride (PVC) tubing. A similar procedure was used for the well-plate study using 150 µL of solution per well, followed by heating at 60 °C.
Biofilm Quantification: PAO1 was added to a 96-well plate or tubes and incubated statically for 24 h. Biofilms were stained with 0.1% crystal violet, solubilized with 33% glacial acetic acid, and measured at OD590 nm.
Cell viability: Colony forming units were measured using 10-fold serial dilutions on TSA agar.
Biofilm formation of PAO1 after incubation with PD-gentamicin coating in PVC tubes
PAO1 biofilm concentration changes with changing the PD to gentamicin ratio during coating synthesis.

Results
PD-gentamicin coated tubes and 96-well plates showed elimination of PAO1 viability at PD concentrations of 0.25 mg/mL and above but had little bactericidal effect at lower concentrations (Fig. 1). There was no reduction in viability in PAO1 exposed to PD or gentamicin alone. PAO1 biofilm was reduced in the median PD-gentamicin concentrations 0.1-0.5 mg/mL, but this effect was lost at the extremes of concentration (Fig. 2).

Conclusion
The PD-gentamicin coating eliminated PAO1 viability and reduced biofilm at PD concentration 0.25 mg/mL. Similar results were observed in 96-well plates and PVC tubes, suggesting versatility in the adherence of the coating material. Additional studies are needed to assess the duration of these effects over time.

Disclosures
All Authors: No reported disclosures
P-1080. Aztreonam-Avibactam Activity Against Gram-negative Bacteria Isolated from Patients with Pneumonia from Europe, Asia, and Latin America (2021–2023)
Authors: Sader Helio S , Kimbrough Hank , Arends S J Ryan , Winkler Marisa , Mendes Rodrigo E , Castanheira Mariana 
Published: January 2025

Abstract

Background
Aztreonam-avibactam (ATM-AVI) is under development to treat Gram-negative (GN) infections. We evaluated the antimicrobial susceptibility of GN bacilli causing pneumonia
Activity of β-lactamase inhibitor combinations

Methods
7,560 organisms were consecutively collected (1/patient) from patients with pneumonia in 59 medical centres located in Western Europe (W-EU; 10 countries; 24 centres; 3,977 isolates), Eastern Europe (E-EU; 9 countries; 15 centres; 1,617 isolates), the Asia-Pacific region (APAC; 7 countries; 12 centres; 1,238 isolates), and Latin America (LATAM; 6 countries; 8 centres; 728 isolates). Isolates were susceptibility tested by broth microdilution. Cefiderocol was only tested against carbapenem-resistant Enterobacterales (CRE). CLSI breakpoints were applied. An ATM-AVI PK/PD susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. CREs were screened for carbapenemase-encoding genes by whole genome sequencing.

Results
ATM-AVI inhibited &gt;99.9% of Enterobacterales (ENT) at ≤8 mg/L (MIC50/90, 0.06/0.25 mg/L) and showed consistent activity across regions (Table). Only 2 ENT had an ATM-AVI MIC &gt;8 mg/L, an E. cloacae (Italy) and a K. pneumoniae (Taiwan). CRE rates ranged from 1.3% (W-EU) to 20.5% (LATAM). Multidrug-resistance (MDR; non-S to ≥3 classes) rates varied from 20.2% (W-EU) to 47.2% (LATAM). ATM-AVI retained potent activity against CRE (MIC50/90, 0.25/0.5 mg/L; 99.7% inhibited at ≤8 mg/L) and MDR ENT (MIC50/90, 0.12/0.5 mg/L; 99.9% inhibited at ≤8 mg/L). Cefiderocol was active against 95.8% of CRE. Ceftazidime-avibactam (CAZ-AVI; 61.7% S), meropenem-vaborbactam (MEM-VAB; 52.8%S), and imipenem-relebactam (IMI-REL; 44.5% S) showed limited activity against CRE and S rates varied greatly among regions. A metallo-β-lactamase was identified in 35.8% of CREs, varying from 23.8% in LATAM to 60.3% in APAC. IMI-REL (95.3% S), CAZ-AVI (94.7% S), and ceftolozane-tazobactam (TOL-TAZ; 93.3% S) were the most active agents against P. aeruginosa; whereas ATM-AVI inhibited 79.5% of isolates at ≤8 mg/L and 76.1% were piperacillin-tazobactam (PIP-TAZ)-S. ATM-AVI inhibited 98.9% of S. maltophilia isolates (n=440) at ≤8 mg/L.

Conclusion
ATM-AVI was the most active compound against CRE and S. maltophilia isolated from patients with pneumonia.

Disclosures
Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for &gt; 30 biotech and pharmaceutical companies: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1088. Safety Study of Rifaquizinone in Dogs Following Intra-articular Administration
Authors: Wang Huan , Cheng Qin , Ke Weijian , 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 sought to investigate the safety/tolerability of RFQ following intra-articular (IA) administration in Beagle dogs.

Methods
Forty Beagle dogs (20/sex) were randomly assigned to 4 groups (5/sex/group) to receive 0, 1, 2.5, and 5 mg/kg/day RFQ in 5% (w/v) glucose once daily for 14 days by IA administration into the right knee joint. All the dogs had a 14-day recovery period to assess the reversibility, persistence, or delayed occurrence of adverse effects. Blood and synovial fluid samples were collected and concentrations of RFQ in each matrix were determined by liquid chromatography tandem mass spectrometry.

Results
No test article-related adverse effects in body weight, food consumption, temperature, clinical pathology, or organ weight were observed in any of the study groups. In 2.5 and 5 mg/kg/day groups, lameness, swelling and ulceration of right knee joint during treatment were observed. The 5 mg/kg group dosing was terminated prematurely due to marked arthritis on right knee joint. The no observed adverse effect level (NOAEL) was 1 mg/kg/day. At this dose level the steady state of RFQ concentrations in synovial fluid was achieved in 4 days and maintained until Day 14 (Figure 1). The mean RFQ concentrations on Day 14 in synovial fluids for male and female dogs were 35,900 and 19,200 ng/mL, respectively, as compared to the plasma Cmax 411 and 303 ng/mL for male and female dogs, respectively. Plasma toxicokinetics (TK) analysis indicated no apparent sex differences in systemic exposure at any dose level.

Conclusion
The NOAEL of RFQ in dogs was 1 mg/kg/day via IA administration. The synovial fluid concentration at this dose level exceeded minimum biofilm bactericidal concentration inhibit 90% bacterial growth (MBBC90) levels for both S. aures and S. epidermidis. IA administration of RFQ is a promising option for the treatment of PJIs.

Disclosures
Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Qin Cheng, Master, TenNor Therapeutics (Suzhou) Ltd: Employee Weijian Ke, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee
P-1096. Activity of Ibrexafungerp and Comparator Antifungals Tested against Candida and Aspergillus Isolates Collected from Invasive Infections in a Global Surveillance Program in 2023
Authors: Winkler Marisa , Rhomberg Paul , Klauer Abigail , Edeker Samuel , Min Sharon , Castanheira Mariana 
Published: January 2025

Abstract

Background
Ibrexafungerp (IBX) is a novel triterpenoid antifungal agent that was approved by the U.S. FDA for the treatment of vulvovaginal candidiasis (VVC) in 2021. Further studies are ongoing to assess the efficacy of IBX for the treatment of invasive candidiasis (IC) and other refractory fungal infections, including aspergillosis. CLSI, EUCAST, or FDA clinical breakpoints or epidemiological cutoff values are not yet defined for IBX against fungi. We evaluated the activity of IBX and comparator agents against clinical isolates from IC and invasive aspergillosis infections collected from a global surveillance program in 2023.
MIC50/90 (mg/L) for ibrexafungerp (IBX) and comparator agents against 5 most common Candida spp., C. auris, and 3 most common Aspergillus spp. in 2023 SENTRY Antifungal Surveillance Program

Methods
A total of 1120 Candida spp. and 204 Aspergillus spp. isolates consecutively collected as part of the SENTRY Program were evaluated. Isolates were recovered from 11 medical centers in North America, 18 in Europe, 7 in Asia-Pacific, and 5 in Latin America. Identification was performed by MALDI-TOF MS and/or sequencing and susceptibility testing was performed using the CLSI broth microdilution method for IBX, anidulafungin (AND), micafungin (MFG), fluconazole (FLC), itraconazole (ITC), and voriconazole (VRC).

Results
Table 1 displays MIC50/90 results for the 5 most common Candida spp., C. auris, and the 3 most common Aspergillus spp. The IBX MIC50/90 results were low against all organisms including organisms of critical concern like C. auris. Among Candida species, IBX had similar or higher MIC50/90 to AND except for C. parapsilosis where IBX MIC50/90 values were 4- to 8-fold lower. MFG was more potent (4- to 16-fold) against most Candida spp. except for C. parapsilosis where IBX had 2-to 4- fold lower MIC50/90 and C. auris where IBX was similar to MFG. Notably, the highest MIC result observed for IBX against C. auris was 1 mg/L. MIC50/90 values for IBX were also 8- to &gt; 256-fold lower than azoles against Aspergillus spp. but higher (2- to ≥ 16-fold) than MFG or AND.

Conclusion
IBX has good activity against the predominant Candida and Aspergillus species from a worldwide contemporary collection. This agent may represent an oral option for the management of difficult-to-treat invasive fungal pathogens such as C. glabrata, C. auris, and Aspergillus spp. from diverse infection sources in addition to its current indication for VVC.

Disclosures
Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for &gt; 30 biotech and pharmaceutical companies: Grant/Research Support Sharon Min, MS, GSK: Employee
P-1098. Clinical outcomes in four patients with refractory Coccidioidal meningitis treated with olorofim
Authors: Yousefzadeh Michelle , Goodman-Meza David , Allyn Paul R 
Published: January 2025

Abstract

Background
Coccidioidal meningitis (CM) remains a highly morbid condition. Olorofim is a novel agent that inhibits the fungal dihydroorotate dehydrogenase enzyme and has potent in vitro activity against Coccidioidomycosis.

Demographics of patients at the time of olorofim initiation with description of prior treatments.

Methods
We performed a retrospective case series of 4 patients with refractory CM treated with olorofim between 2020 and 2024 comparing outcomes assessed by symptoms, brain imaging, and Mycosis Study Group (MSG) score.

Change in Symptoms, MRI Brain Imaging, MSG Score, and CSF Parameters after Olorofim Initiation. Abbreviations: CF, Coccidiodes complement fixation; CSF, cerebrospinal fluid; MRI, magnetic resonance imaging, MSG, Mycosis Study Group (MSG).

Results
At baseline, mean age was 53 (range 41-66), mean time since diagnosis 950 days (range 378-1591), mean MSG score 5.8 (range 3-11), and mean azoles failed 3.25 (range 2-4). Follow-up occurred at variable intervals for a total duration of 332-985 days on therapy. In early follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 2 patients and stable in 1; mean MSG score was 4.75, decreased in 1 patient, unchanged in 1, and increased but low in 2. In late follow-up, symptoms were improved in 3 patients and stable in 1; available imaging was improved in 1 patient and stable in 1; mean MSG score was 2.7, decreased in 2 patients, unchanged in 1, and increased in 1. Patient 3 developed significant transaminitis requiring dose reduction at day 91 with subsequent relapse (MSG score 14) but was eventually stabilized on combination therapy with fluconazole.

Cerebral spinal fluid (CSF) complement fixation, glucose, protein and white blood cell count (WBC) graphed over time on antifungal treatment. Time 0 represents initiation of olorofim.

Conclusion
At last follow-up, 2 patients were doing well with improvement or stability in all domains, 1 patient died of unrelated causes, and 1 patient had late treatment failure after prolonged stability for 2.5 years. Olorofim may be an effective alternative treatment for patients with refractory CM.

Mycosis Study Group (MSG) scores plotted over time. The plot excludes an MSG score of 14 for patient 3 shortly after Early follow-up period during a temporary hold on olorofim administration due to medication induced transaminitis.

Disclosures
All Authors: No reported disclosures
415. Optimizing Blood Culture Utilization in Solid Organ Transplant Recipients: A Diagnostic Stewardship Approach
Authors: Steinbrink Julie M , Mehdiratta Nitin , Pena Heather E , Welsby Ian , Seidelman Jessica , Carugati Manuela 
Published: January 2025

Abstract

Background
Diagnostic stewardship of blood culture utilization is paramount to mitigate the risks associated with excessive culturing, including increased contamination rates and inappropriate antimicrobial administration. Although blood culture algorithms have been studied previously, there is insufficient data on their application specifically in solid organ transplant recipients. This study aims to retrospectively apply a blood culture algorithm (initially developed for a non-immunocompromised population) to assess its effectiveness in this immunosuppressed population.
Figure 1. Algorithm used by clinical providers to determine if blood cultures are appropriate or inappropriate

Methods
We conducted a retrospective review of adult solid organ transplant recipients with a blood culture event (BCE) occurring between February 2022 to January 2024 at a single academic medical center. A BCE was defined as the collection of at least one blood culture set for a specific clinical indication. During this time a blood culture algorithm (Figure 1) was implemented across 12 units in the hospital. Patient charts were manually reviewed to categorize BCEs as appropriate (the algorithm agreed with obtaining a blood culture), inappropriate (if the algorithm suggested to not draw a blood culture), or lacking documentation.

Results
Among 824 BCEs recorded in adult solid organ transplant recipients (Figure 2), 669 (81.2%) were deemed appropriate, 118 (14.3%) were inappropriate, and 37 (5.5%) lacked sufficient documentation. Adjudication of 388 BCEs with available data was performed and revealed 350 (90.2%) negative cultures, 25 (6.4%) true positives, and 13 (3.4%) contaminants (Figure 3). Within the subset of inappropriate BCEs (n=118), 113 (95.8%) yielded negative cultures, while 5 (4.2%) were contaminants; no true positives were identified.

Conclusion
The retrospective application of the blood culture algorithm did not reveal any missed true positive bacteremias in solid organ transplant recipients. Although this study is limited in scope, it provides initial evidence supporting the cautious application of the algorithm in this population. As a next step, we will adjudciate the remaining 436 BCE in the dataset. Further investigation is warranted to validate these findings and optimize diagnostic stewardship strategies for improved patient outcomes.

Disclosures
Jessica Seidelman, MD, MPH, 3M: Expert Testimony
P-1102. Real-World Effectiveness of Dalbavancin for Invasive Gram-Positive Bacterial Infections
Authors: Crocker Jake , Derrick Caroline , Justo Julie Ann , Brandon Bookstaver P , Yunusa Ismaeel , Jones Bruce M , White Bryan , Sassine Joseph , Belk Madeline , Pizzuti Morgan 
Published: January 2025

Abstract

Background
Emerging data suggest dalbavancin (DAL) may be used in complicated infections including bacteremia, prosthetic joints, osteomyelitis, and endovascular infections. The purpose of this study was to evaluate the real-world effectiveness of DAL for the treatment of invasive gram-positive infections (GPIs).

Methods
This multicenter, retrospective cohort study included adult patients receiving DAL for treatment of confirmed/presumed invasive GPI between February 2021 and December 2023. Invasive infections included those requiring ≥ 4 weeks of therapy. Patients were excluded if they received DAL for chronic suppression. The intention to treat (ITT) population included patients who received ≥ 1 DAL dose; the per protocol (PP) population received ≥ 2 doses within 7 days of expected administration dates. The primary outcome was clinical failure in the PP group at 90 days post-treatment. Secondary outcomes were logistical failures, clinical failures, and treatment-emergent adverse events in the ITT group at 90 days post-treatment.

Results
The ITT population included 150 patients (mean age 50.2 years, 65% male, 35% obese, 41% illicit drug use); the PP population included 107 patients. The most common infectious syndrome was osteomyelitis (63.3%, 95/150); the most common pathogens were MRSA (38%, 57/150) and MSSA (37%, 44/150). The most common dosing regimen was 1500 mg on day 1, followed by 1500 mg on day 8 (90%, 96/150). Among the PP population with follow-up, 22% (19/87) experienced clinical failure at 90 days post-treatment. No factors were significantly associated with clinical failure. Logistical failure occurred in 17% (26/150). Results of univariate regression analyses showed receipt of first dose at an infusion center vs. inpatient setting significantly increased logistical failure (OR 4.53, 95% CI 1.62 – 16.17; P = 0.008) while blood-based infectious syndromes significantly decreased logistical failure (OR 0.26, 95% CI 0.06 – 0.82; P = 0.038). Receipt of vancomycin within 6 weeks of DAL significantly increased risk of acute kidney injury (OR 4.12, 95% CI 1.20 – 14.68; P = 0.024).

Conclusion
Dalbavancin is a safe and effective treatment option for invasive GPIs; however there are modifiable risk factors associated with secondary outcomes of logistical failure and toxicity.

Disclosures
Julie Ann Justo, PharmD, MS, FIDSA, BCPS, Shionogi: Advisor/Consultant Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Ferring: Honoraria|Innoviva: Honoraria|Paratek: Honoraria Bryan White, PharmD, BCPS, BCIDP, Melinta: Advisor/Consultant|Shionogi: Grant/Research Support Joseph Sassine, MD, Ansun BioPharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|Community Infusion Solutions: Grant/Research Support|F2G: Grant/Research Support|Shionogi: Grant/Research Support
P-1119. The role of Carbapenemase gene detection and synergy testing in invasive infections caused by Carbapenem resistant Enterobacterales in the pediatric population at a quaternary hospital in South India
Authors: Deshpande Sanjay , Iyer Ranganathan 
Published: January 2025

Abstract

Background
The incidence and prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infections in children is increasing globally. However, there are limited studies that address clinical, microbiological profiles, molecular and synergy testing of these CRE infections, in this population. Our study was aimed at studying the clinical profile, microbiological and molecular diagnoses, and synergy testing of CRE bacteremia in children admitted to the intensive care unit (ICU).

Methods
Medical records of children admitted to the ICU with CRE bacteraemia over a year were reviewed. Their clinical background, microbiological diagnoses, molecular profile, antibiotic resistance patterns, synergy testing, and clinical outcomes were analyzed. Carbapenemase genes were detected using Gene X pert (Cepheid) and synergy testing was carried out on those isolates with New Delhi Metalloproteinase (NDM). NDM-1 or NDM + Oxacillinase (OXA) OXA-48 genes. The results were expressed as fractional inhibitory concentration index (FICI) and the same was correlated with treatment using Ceftazidime- Avibactam+/- Aztreonam.

Results
98 children with blood stream infections (40 in neonatal ICU and 58 pediatric ICU) were identified. K. pneumoniae accounted for a majority of BSI’s (n-34 in neonatal ICU and n- 47 in pediatric ICU) with most of them expressing the NDM gene (50%). The overall Colistin resistance across both ICU’s was (MIC &gt; 2 ug ml) was 0.03%. Synergy to Ceftazidime-Avibactam- Aztreonam could be demonstrated in a majority of CREs which were NDM / NDM+OXA-48 producers (82.3% K. pneumoniae in neonatal ICU and 90% in pediatric ICU). Eight neonates (20%) and seventeen children (29%) succumbed due to other comorbidities, all of whom had NDM Klebsiella pneumoniae bacteraemia (n-17, 100%).

Conclusion
NDM producing Klebsiella pneumoniae remains the commonest identified BSI in neonatal and paediatric patients in the intensive care and was isolated in all children with adverse outcomes. Infection control, antimicrobial stewardship protocols and Carbapenemase gene detection with targeted synergy and directed therapy is recommended for favorable clinical outcomes of BSI’s in the critically ill children.

Disclosures
All Authors: No reported disclosures