bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1018. A comprehensive strategy identifies Candida albicans genes and biologic processes that contribute to pathogenesis of intra-abdominal candidiasis (IAC)
Authors: Clancy Cornelius J , Cheng Shaoji , Nguyen Minh-Hong 
Published: January 2025

Abstract

Background
IAC pathogenesis is poorly understood.Figure 1.C. albicans transcription factor mutants attenuated during IAC.

Methods
We used RNA-Seq to measure C. albicans SC5314 gene expression during early peritonitis (30-min), late peritonitis (24-hr) and abscesses (IAA; 48-hr) of mice. ≥2-fold differences were significant (false discovery ≤0.01). We screened duplicate signature-tagged, homozygous deletion libraries for 165 C. albicans transcription factors (TFs) in 72-hr IAA.

Results
The 50 genes most highly expressed during early peritonitis were associated with pH (e.g., RIM101, PHR1), oxidative stress responses (e.g., SOD4-6), and adhesion/hyphal growth (e.g., ALS3, HWP1, ECM331, SAP6). The corresponding 50 late peritonitis genes were associated with phagocyte responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism. Null mutants for genes involved in adhesion (ALS1, ALS3), transport (OPT8, SGE11), biofilm (ZCF23), DNA damage responses (RFX1, RFX2, DDI1), cell wall responses (DAP2) and copper metabolism (CCC2) were attenuated during peritonitis and/or IAA [Table 1]. 21 TF mutants were significantly attenuated for virulence in both libraries [Fig 1]. Biologic processes over-represented were regulation of pH responses, biofilm, hyphal formation, echinocandin responses, and copper metabolism. 9 pH response regulators were confirmed to contributed to virulence, including RIM101, STP2 (alkaline), ASH1, SFL1, SFL2 (neutral), MNL1, SKO1, PHO4 (weak acid), and CSR1 (acid) [Fig 2]. Over-expression of aspartyl protease SAP5 in rim101 restored virulence during IAA at 3, 7, and 10 days. Over-expression of either SKO1 or PHO4 in mnl1 restored weak acid responses in vitro [Fig 3] and virulence (not shown).Figure 3.Over-expression of PHO4 or SKO1 in mnl1 rescues weak acid responses

Conclusion
Numerous C. albicans environmental response genes make temporal-spatial contributions to IAC. pH response regulators RIM101 and MNL1 contribute to virulence during peritonitis and IAA, in part by regulating SAP5 and PHO4/SKO1, respectively. Other processes and genes involved in IAC pathogeneses are adhesion, transport, biofilm, DNA damage responses, cell wall responses and copper metabolism.

Disclosures
Cornelius J. Clancy, MD, Cidara: Grant/Research Support|Gilead: Honoraria|Merck: Grant/Research Support|Scynexis: Advisor/Consultant|Shionogi: Advisor/Consultant|Venatorx: Advisor/Consultant
P-1019. Incidence And Risk Factors for Invasive Fungal Infections in Pre-Transplant and Transplant-Ineligible Multiple Myeloma in the U.S.: A Claims Analysis (2017-2021)
Authors: Rogers Daniel , Baker Aubrey N , Xu Jianing , Chen Xianyan , Henao Martínez Andrés F , Chastain Daniel B 
Published: January 2025

Abstract

Background
Current research on risk factors for invasive fungal infections (IFIs) in multiple myeloma (MM) has limitations due to heterogeneous patient populations, including post-transplant, or reliance on subgroup analyses. This study aimed to address this gap by evaluating the incidence of IFIs and identifying risk factors in patients with MM receiving treatment before or ineligible for transplant.

Methods
We analyzed data from the Merative MarketScan Database (2017-2021) to identify adults (≥ 18 years) diagnosed with and treated for MM with proteasome inhibitors, lymphodepleting agents, thalidomide or derivatives, anti-SLAMF7 monoclonal antibodies, or exportin 1 inhibitors, with or without dexamethasone. We evaluated the incidence and risk factors for IFIs following anti-MM therapy initiation. All patients were followed for at least one year. Patients without an IFI were censored at the end of the study period.

Results
Among 3054 individuals with MM, 6% (n=195) were diagnosed with an IFI. Candidiasis was most common (87%), followed by pneumocystis (6.2%) and aspergillosis (3.6%). Patients with an IFI were younger with a higher burden of comorbidities compared to those without an IFI (table 1). Notably, neutropenia, thrombocytopenia, chronic heart failure, chronic liver failure, hypercalcemia, and hyperglycemia were significantly more common in the IFI group. Anti-MM therapies were similar between groups, with a high prevalence of both thalidomide or derivatives and dexamethasone (table 2). Antifungal prophylaxis was uncommon while nearly half of each group received antibacterial prophylaxis. Patients with an IFI were more likely to have received multiple lines of anti-MM therapy. Multivariate analysis identified recent dexamethasone use (HR 5.85, 95% CI: 4.08-8.40), neutropenia (HR 2.77, 95% CI: 1.87-4.11), and a greater number of anti-MM therapies within the preceding year (HR 2.15, 95% CI: 1.71-2.69) as significant risk factors for IFI.

Conclusion
Candidiasis was the most common IFI in patients with MM. Younger age, higher comorbidity burden, and neutropenia were associated with IFIs. Additionally, recent dexamethasone use and a higher number of prior anti-MM therapies significantly increased the risk of IFIs.

Disclosures
All Authors: No reported disclosures
P-1040. Clinical Outcomes of Micafungin for Invasive Fungal Infections in the Obese and Nonobese
Authors: Moran Ryan , Cady Beth 
Published: January 2025

Abstract

Background
The efficacy and safety of echinocandins make them favorable first-line options for many fungal infections. Current guidelines do not recommend dose adjusting echinocandins for obesity. Increasing evidence suggests pharmacokinetic goals may be difficult to attain with standard echinocandin dosing in obese populations but clinical outcomes data is scarce. The purpose of this study is to investigate if obese patients given micafungin for invasive fungal infection (IFI) have worse outcomes compared to nonobese patients.

Methods
This retrospective study compared obese and nonobese patients receiving micafungin for IFI. Primary outcome was favorable clinical response in obese patients compared to nonobese patients with IFI at the end of antifungal therapy. Inclusion criteria were age ≥ 18, suspicion of IFI, and receipt of micafungin for ≥ 72 hours. Doses other than micafungin 100 mg were excluded. Patients were placed into one of two groups. Patients with a body mass index (BMI) &lt; 30 kg/m2 were assigned to the nonobese group and those with a BMI ≥ 30 kg/m2 were assigned to the obese group.

Results
600 patients were evaluated resulting in 378 being included with 177 and 201 in the obese and nonobese groups, respectively. There were minor variations in baseline characteristics. The primary outcome occurred in 49% in the obese group and 51% in the nonobese group (p=0.76).

Conclusion
These results do not show a difference in clinical outcomes using micafungin in obese and nonobese patients and do not support use of higher doses of micafungin in the obese. It is unknown whether there is truly no difference or if no difference was seen due to small sample size. Additional research is needed to further evaluate echinocandins and clinical outcomes in obese patients.

Disclosures
All Authors: No reported disclosures
P-1044. Physician's Compliance to Clinical Practice Guidelines and Outcomes of Patients with Invasive Candidiasis at A University Hospital in Thailand
Authors: Pirogard Nantaporn , Chongtrakool Piriyaporn , Chayakulkeeree Methee 
Published: January 2025

Abstract

Background
Compliance to the clinical practice guidelines (CPG) has shown to reduce mortality in patients with invasive candidiasis (IC). This study aimed to evaluate the physician’s compliance to locally developed CPG after implementation of care bundles and patient’s outcomes.

Methods
This is a quasi-experimental study using historical cohort control. Candidemia patients admitted during November 2021 to April 2024 were enrolled. The CPG for IC was implemented in the prospective cohort. Care bundles were implemented. Each eight CPG item was given a value for poor to good compliance ranging from 0 to 2, and the compliance score was calculated. Compliance score &lt; 8 was considered as poor compliance. Physician’s compliance and all cause 30-day mortality were analyzed.

Results
A total of 109 patients were included, 56 in historical control and 53 in prospective intervention group. Patients in both groups showed similar baseline characteristics and risk factors for candidemia. After the implementation of the CPG and care bundles, the physician’s compliance increased significantly, including early treatment within 24 hours (OR = 5.63, 95% CI [2.25-14.01], p-value &lt; 0.001), receipt of appropriate antifungal therapy (OR = 8.67, 95% CI [1.05-71.88], p-value 0.03), source control within 48 hours (OR = 34.70, 95% CI [4.36-276.10], p-value &lt; 0.001), obtaining blood culture every other day (OR = 17.93, 95% CI [6.90-46.82], p-value &lt; 0.001), antifungal therapy at least 14 days after negative blood culture (OR = 2.76, 95% CI [1.20-6.33], p-value 0.02), echocardiography (0% vs 17%, p-value 0.001), and fundoscopy (OR = 5.25, 95% CI [1.78-15.45], p-value 0.001). There was significant improvement in compliance score of ≥ 8 in the intervention group (OR = 5.07, 95% CI [1.86-13.84], p-value 0.001). Mean ± SD of the compliance score was 8 ± 2 in the control group and 11 ± 2 in the intervention group (p-value 0.001). All cause 30-day mortality rate significantly decreased from 55.4% in the control group to 35.8% in the intervention group (OR = 0.45, 95% CI [0.21-0.97], p-value 0.04).

Conclusion
CPG and care bundles for IC significantly improved physician’s compliance and patient’s survival, encouraging the implementation of the CPG and care bundles for the management of IC.

Disclosures
All Authors: No reported disclosures
P-1069. Comparative Antibacterial Activity of Hypochlorous and Polygalacturonic + Caprylic Acids in an In Vitro Wound Biofilm Model
Authors: Gerges Bahgat Z , Raad Issam I , Jiang Ying , Rosenblatt Joel , Truong Y Lan 
Published: January 2025

Abstract

Background
Therapeutic agents which impart minimal inflammatory responses are needed to disinfect microbially contaminated chronic wounds. Polygalacturonic + caprylic (PG+CAP) and hypochlorous (HOCl) acids have been shown to be well tolerated potent antimicrobial agents for eradicating a broad range of microbial biofilms in standard in vitro biofilm models. However, standard microbiologic biofilm eradication models do not present the complex natural environments of chronic wound beds which contain significant quantities of human proteins. In this study we compared the efficacy of PG+CAP and HOCl against resistant wound biofilm bacterial pathogens in a 3-dimensional fibrin gel wound biofilm model, which is more realistically simulates a colonized chronic wound.

Methods
A fibrin gel biofilm eradication model was used to quantify antibacterial efficacy. Forty-eight hours mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa were allowed to form on fibrin gels creating wound biofilm models. They were then exposed to 1% PG+ 0.8% CAP or 400 ppm HOCl for three hours. Following exposure, the wound gels were sonicated in neutralizer broth, then serially diluted, plated and counted to enumerate viable colonies (CFU/mL). Positive controls were not exposed to antimicrobial agents. Statistical comparisons of six-replicates for each group were performed using Wilcoxon rank sum test (p&lt;0.05 is considered statistically significant).

Results
Figure 1 presents the median number of CFU/mL recovered from controls and wound biofilms exposed to PG+CAP, and HOCl.

Conclusion
PG+CAP completely eradicated S aureus biofilms with greater than 7-log reduction in CFU/mL versus positive control, while HOCl produced a 4.2 log reduction. The CFU/mL difference between PG+CAP and HOCl was significant (P= 0.0028). For P. aeruginosa, PG+CAP and HOCl produced 8.28 and 2.32 log reductions versus positive control respectively with a significant difference in CFU/mL between them (P= 0.0043). These results suggest microbiologic testing in wound biofilm models may be important to realistically test the efficacy of antimicrobial agents for chronic wound care. These results suggest PG+CAP merits further testing for disinfecting contaminated chronic wounds.

Disclosures
All Authors: No reported disclosures
P-1081. Activity of Aztreonam-Avibactam against Enterobacterales Isolated from Patients with Intra-Abbdominal Infection from United States Medical Centers (2019-2023)
Authors: Sader Helio S , Doyle Timothy , Mendes Rodrigo E , Winkler Marisa , Castanheira Mariana 
Published: January 2025

Abstract

Background
Aztreonam-avibactam (ATM-AVI) is being developed for the treatment of Gram-negative infections, including those caused by metallo-β-lactamase (MBL) producers. We evaluated the activity of ATM-AVI against Enterobacterales (ENT) isolated from patients with intraabdominal infections (IAI) in United States (US) medical centers.
Activity of β-lactamase inhibitor combinations against Enterobacterales from intra-abdominal infections

Methods
2,036 isolates (1/patient) were consecutively collected from patients with IAI in 63 US hospitals in 2019-2023. Susceptibility testing was performed by broth microdilution method. ATM-AVI was tested with AVI at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. Carbapenem-resistant ENT (CRE) were screened for carbapenemases (CBase) by whole genome sequencing. Comparator agents included ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and cefiderocol (CRE only), among others.

Results
The most common ENT species were E. coli (47.1%), K. pneumoniae (18.7%), and E. cloacae species complex (9.8%). Only 1 ENT exhibited ATM-AVI MIC &gt;8 mg/L (MIC50/90, ≤0.03/0.12 mg/L), an E. coli with ATM-AVI MIC of 16 mg/L. The most active agents against CRE were ATM-AVI (93.3% inhibited at ≤8 mg/L) and cefiderocol (93.3% S); CAZ-AVI, MEM-VAB, and IMI-REL were active against 86.7% of CRE (Table). A multidrug-resistant (MDR) phenotype (non-S to ≥3 classes) was observed in 21.4% of ENT (n=436) and the most active β-lactamase inhibitor combination (BLIC) against MDR isolates were ATM-AVI (99.8% inhibited at ≤8 mg/L), MEM-VAB (99.5% S), and CAZ-AVI (99.3% S). Piperacillin-tazobactam (PIP-TAZ) was active against 87.2% of ENT and 50.2% of MDR, and meropenem was active against 92.2% of ENT and 96.1% of MDR. A CBase was identified in 9 isolates (60.0% of CRE), and included KPC-2 (3 isolates), KPC-3 (4), and NDM-5 (2). All CBase producers were inhibited at ≤8 mg/L of ATM-AVI and were cefiderocol-S; whereas susceptibility to CAZ-AVI, MEM-VAB, and IMI-REL were 77.8%.

Conclusion
ATM-AVI and the newer BLICs exhibited almost complete activity against ENT causing IAI in US hospitals. ATM-AVI may represent a valuable treatment option for IAI, including those caused by CRE and MDR ENT.

Disclosures
Rodrigo E. Mendes, PhD, GSK: Grant/Research Support 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
P-1082. Antimicrobial Susceptibility of Enterobacterales Causing Infection in the Elderly: Focus on Aztreonam-avibactam and Recently Approved β-Lactamase Inhibitor Combinations
Authors: Sader Helio S , Mendes Rodrigo E , Doyle Timothy , Winkler Marisa , Castanheira Mariana 
Published: January 2025

Abstract

Background
Infections account for about 1/3 of all deaths in people 65 years and older and this population has a higher risk of exposure to antimicrobial-resistant bacteria. We evaluated the antimicrobial susceptibility of Enterobacterales (ENT) causing infection in elderly patients in United States (US) medical centers.
Activity of β-lactamase inhibitor combinations against Enterobacterales from elderly patients

Methods
Clinical isolates (1/patient) were consecutively collected from 72 US medical centers in 2021-2023 and susceptibility tested by broth microdilution. Results for 10,574 ENT isolates from elderly patients (≥65 years old) were analyzed and compared to 9,793 isolates from adult patients (age 18-64). Results were stratified by infection type and resistant subsets. Cefiderocol was only tested against carbapenem-resistant ENT (CRE). ATM-AVI was tested with AVI at fixed 4 mg/L and a PK/PD susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. CRE isolates were screened for carbapenemases (CBase) by whole genome sequencing. Comparator agents included ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MEM-VAB), imipenem-relebactam (IMI-REL), and cefiderocol (CRE only), among others.

Results
All elderly isolates were inhibited at ATM-AVI MIC of ≤8 mg/L. CAZ-AVI (99.7% S) and MEM-VAB (99.8% S) were very active against ENT overall but exhibited limited activity against CRE (71.6% and 70.4% S, respectively; Table). The most active agents against CRE were ATM-AVI (100.0% inhibited at ≤8 mg/L) and cefiderocol (96.3% S). Multidrug-resistant (MDR; non-S to ≥3 classes) and ESBL phenotypes were observed in 19.8% and 12.3% of isolates, respectively, and ceftolozane-tazobactam (TOL-TAZ) and piperacillin-tazobactam (PIP-TAZ) showed limited activity against these organisms. Susceptibility to TOL-TAZ, PIP-TAZ, and ceftriaxone were lower among elderly isolates from pneumonia than BSI or UTI. The most common CBase were KPC (56.8% of CRE) and NDM (22.2%). A metallo-β-lactamase was identified in 24.7% of isolates. In general, susceptibility rates of isolates from the elderly were comparable (+/- &lt; 2%) to those from the adult population.

Conclusion
ATM-AVI demonstrated complete activity (100.0% S) against ENT causing infection in the elderly, including CRE and isolates with ESBL or MDR phenotypes.

Disclosures
Rodrigo E. Mendes, PhD, GSK: Grant/Research Support 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
P-1091. Hydrogen peroxide generating electrochemical bandage for the treatment of wound biofilm infections - preliminary demonstration of device safety on healthy human skin
Authors: Kies Paige , Fleming Derek , Kim Won-Jun , Anoy Md Monzurul , Bozyel Ibrahim , Holtegaard Susan , Greenwood-Quaintance Kerryl , Beyenal Haluk , Patel Robin 
Published: January 2025

Abstract

Background
Wound biofilm infections impact ∼2% of the United States and at-risk individuals often have underlying morbidities such as diabetes. Antibiotics and topical approaches like debridement or silver dressings have had limited success, underscoring a need for strategies that efficiently target pathogens in wound beds.

Methods
We developed a hydrogen peroxide (H2O2) generating electrochemical bandage (e-bandage) composed of carbon fabric electrodes separated by cotton fabric with an Ag/AgCl reference electrode (RE) placed between cotton fabric layers. The e-bandage is controlled by a wearable micropotentiostat (MP); H2O2 is generated by O2 + 2H++ 2e- → H2O2. O2 is dissolved on a primary working electrode with negative polarity compared to the RE while a positively polarized secondary counter electrode generates H+ and e-. The H2O2 e-bandage/MP device has in vitro activity against mono- and dual-species bacterial and fungal biofilms. We showed that the H2O2 e-bandage decreased the burden of methicillin-resistant Staphylococcus aureus and/or Pseudomonas aeruginosa with difficult-to-treat resistance in a murine wound infection model. Given this, we initiated a H2O2 e-bandage safety assessment on healthy human skin. Here, testing of a non-polarized, circular (2 cm diameter) device pre-loaded with biocompatible hydrogel containing 0.9% NaCl is reported. Sterilized e-bandages assessed in a shelf-life study retained activity for two weeks. Adults with intact forearm skin were then recruited to the Clinical Research Trials Unit at the Mayo Clinic. Consented individuals had a non-polarized e-bandage covered by Tegaderm placed on their forearm. A MP enclosed in a biocompatible case was connected to the e-bandage and secured using skin tape. One day later, the device was removed and a follow-up phone call made six days later to assess for adverse effects.

Results
Three volunteers wearing a non-polarized H2O2 e-bandage experienced no discomfort, irritation, allergic reaction, or skin discoloration after device removal and seven days post device placement.

Conclusion
These preliminary studies combined with the previously performed murine bacterial biofilms work support further studies of this novel device for treating wound infections caused by antimicrobial resistant pathogens.

Disclosures
Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria
P-1108. Efficacy and Safety of Investigational Therapeutic Microbiome SER-109 in Recurrent Clostridioides difficile Infection: A Systematic Review
Authors: Fabara Stephanie P , Alok Akankcha , Kalsi Harsimran , Bakhit Mohamed , Thomas Sanil 
Published: January 2025

Abstract

Background
Current therapies for recurrent Clostridioides difficile infection (CDI) often fail to address the disrupted microbiome contributing to C. difficile spore germination and subsequent toxin production. SER-109, an investigational therapeutic microbiome, is composed of purified Firmicutes spores and shows promise in treating recurrent CDI. Our aim was to evaluate the efficacy, safety and recurrence rate of CDI following administration of oral SER-109.Figure 1.Selection of studies using a PRISMA flow chart.

Methods
We systematically reviewed available literature on PUBMED using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for clinical trials involving SER-109 (Figure 1). We found three clinical trials that met our inclusion criteria and primary efficacy endpoint criteria (Table 1). For assessing bias, we used the Cochrane Collaboration's tool risk assessment of the clinical trials (Figure 2).Table 1.Inclusion criteria and primary efficacy endpoint

Results
Oral SER-109 was well tolerated with the rate of recurrent CDI remaining low, regardless of the number of prior recurrences or patient demographics. The diagnostic approach did not significantly impact the beneficial effect of SER-109. In patients with symptom resolution of C. difficile infection after treatment with standard-of-care antibiotics, oral administration of SER-109 was superior to placebo in reducing the risk of recurrent infection. The observed safety profile of SER-109 was mild and similar to that of placebo. Our findings are summarized in Table 2.Figure 2.Bias analysis of the clinical trials in the systematic review.

Conclusion
SER-109 holds promise as a safe and effective treatment for recurrent CDI. Further research is warranted to confirm its long-term efficacy and explore potential mechanisms underlying its impact on the disrupted gut microbiome.Table 2.Characteristics and outcomes of selected studies.

Disclosures
All Authors: No reported disclosures