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Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of orthopedic implant-associated infection, where S. aureus can survive intracellularly and form biofilms. Vancomycin has poor activity against staphyloccoccal biofilms. Although rifampin is effective against staphylococcoal biofilms and has intracellular activity, resistance may develop when it is used as a single agent. Contezolid is a novel oxazolidinone with reported activity against S. aureus in vitro and in vivo in both murine systemic and thigh infection models. Here, we assessed the in vivo activity of contezolid, with and without rifampin, in a rat model of foreign body osteomyelitis. Figure 1. Quantities of MRSA IDRL-6169 recovered from A. tibia B. K-wire. Circles represent values from individual animals; horizontal lines represent mean values. Compared to no treatment: *p=0.0186 **p<0.0002 Methods The left tibia of 60 male Wister rats were inoculated with arachidonic acid (sclerosing agent) and 106 cfu MRSA IDRL-6169 and a K-wire implanted. After four weeks, rats received either no treatment, contezolid (50 mg/kg orally, every 12 h), rifampin (10 mg/kg intraperitoneally every 12 h), rifampin plus contezolid, or vancomycin (75 mg/kg intraperitoneally, every 12 h) plus rifampin for 21 days. Following treatment, tibiae were harvested and cyropulverized. Tibiae and K-wires were cultured separately, and results reported as log10 cfu/gram of bone or K-wire (limit of detect 0.1 log10), respectively. Wilcoxon rank-sum test and false discovery rates were performed and p< 0.05 considered significant. Results Results are shown in Figure 1. MRSA was recovered from tibiae and K-wires of all untreated animals, at means of 5.1 log10 cfu/bone and 3.0 log10 cfu/K-wire, respectively. There was a 1.0 log10 cfu/g mean reduction in MRSA recovered from the tibiae of contezolid-treated rats compared to untreated rats (p=0.0186), and a 0.2 log10 reduction on K-wires. No MRSA was recovered from the tibiae or K-wires in animals receiving rifampin, whether alone or in combination with contezolid or vancomycin. Conclusion Contezolid was active against MRSA in a rat model of foreign body osteomyelitis, reducing bacterial loads in bone, albeit not on K-wires, unless co-administered with rifampin. 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

Abstract Background Small colony variants (SCVs) of Staphylococcus aureus (SA) have significant intracellular persistence. Fluoroquinolones demonstrate intracellular activity and are often utilized to treat SCVs. Delafloxacin is a fluroquinolone with increased potency at a low pH, which could lead to enhanced intracellular activity. This study evaluates delafloxacin activity against intracellular MSSA and MSRA SCV isolates.Figure 1.Illustration of SCV co-culture methods Methods Six clinical SCV-SA isolates were co-cultured with human macrophages for 1 hour, allowing for phagocytosis (Fig 1). The remaining extracellular bacteria were removed and antibiotic treatments of delafloxacin, levofloxacin, gentamicin, cefazolin, or vancomycin were added. After 5-hour and 24-hour incubation periods, supernatants were collected for extracellular colony forming unit (CFU) enumeration. Macrophages were washed, lysed, collected, and plated for intracellular bacterial CFU enumeration. All conditions were repeated in triplicate and compared using a Mann Whitney U test.Figure 2.Intracellular SCV-MSSA CFUs Results Delafloxacin resulted in a 1.9-log reduction in intracellular CFUs (p< 0.001) at 5 hours and a 3.4 log reduction (p< 0.001) at 24 hours compared to antibiotic-free control for MSSA strains (Fig 2). Similarly, levofloxacin resulted in a 1.6-log (p< 0.001) and 1.9-log (p< 0.001) reduction in CFUs after 5 and 24 hours, respectively. Delafloxacin was more effective at clearing intracellular bacteria than levofloxacin at 24 hours (p= 0.004). In MRSA-SCV isolates, delafloxacin demonstrated CFU reduction of 2.4-log (p< 0.001) at 5 hours and 4.7-log (p< 0.001) at 24 hours compared to antibiotic-free control (Fig 3). Levofloxacin demonstrated a 1.6-log (p< 0.001) reduction at 5 hours and 1.5-log (p= 0.034) reduction at 24 hours. In comparison to levofloxacin, delafloxacin led to greater reductions in MRSA CFUs at both 5 hours and 24 hours of incubation, 0.85-log (p= 0.028) and 3.2-log (p< 0.001) respectively.Figure 3.Intracellular SCV-MRSA CFUs Conclusion The results demonstrate delafloxacin having greater intracellular activity than levofloxacin and other comparator antibiotics against both MSSA and MRSA SCVs. These results support using delafloxacin to treat recurrent or chronic infections caused by either MSSA or MRSA SCVs and suggest that the observed efficacy may be a result of enhanced intracellular activity. Disclosures All Authors: No reported disclosures

Abstract Background Pharmacokinetics of beta-lactams vary widely in neonatal and pediatric patients due to developmental biology and critical illness. Cefepime (FEP), meropenem (MEM), and piperacillin/tazobactam (TZP) are highly susceptible to pharmacokinetic changes as hydrophilic, small molecules with renal clearance. Subtherapeutic levels are associated with clinical and microbiologic failure, and supratherapeutic levels associated with toxicity. Beta-lactam therapeutic drug monitoring (TDM) may optimize the effectiveness and safety of these agents. The purpose of this investigation is to describe the % of pediatric and neonatal patients with beta-lactam serum levels within target range. Methods In August 2023, TDM launched at the Mayo Clinic Children’s Center for select patients treated with FEP, MEM, or TZP with expected durations ≥ 48 hours, or who were on kidney replacement therapy (KRT), extracorporeal membrane oxygenation (ECMO), weighed > 120 kg, had a BMI > 95th percentile, or at the discretion of pediatric ID team. Validated drug assays were performed daily, Monday through Friday. A two-level sampling strategy was preferred with a peak 1 hour after the end of the infusion and a trough 30 minutes before the next dose. Empiric trough target ranges were set at FEP 8-50 mg/L, MEM 2-30 mg/L, and piperacillin 16-150 mg/L. These target ranges were adjusted with confirmed microbiology to a time above the minimum inhibitory concentration of the organism for 100% of the dosing interval (100%T > MIC). Results From August 2023 to April 2024, 74 episodes of TDM were performed on 45 patients. Thirty-seven (82%) patients were in an intensive care unit (ICU) at the time of TDM, 8/45 (22%) of whom were in the neonatal ICU. Target range was achieved in 67% of patients on FEP, 50% on MEM, and 52% on TZP. Median (IQR) trough values were 22.1 (8.6, 44.2) mg/L for FEP, 0.6 (0, 4.1) mg/L for MEM, and 15.5 (3.8, 27.1) mg/L for TZP. Seven levels were above target for FEP and 0 for MEM and TZP. Seven levels were below target for FEP, 4 for MEM, and 11 for TZP. Conclusion Implementation of a TDM program for FEP, MEM and TZP in pediatric and neonatal patients revealed drug levels frequently outside target range. TDM may facilitate dose individualization to optimize medication efficacy and minimize toxicity. Disclosures Raymond Stetson, MD, MS, Moderna: Grant/Research Support Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Erin F. Barreto, PharmD, MSc, Baxter Health: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant

Abstract Background At the time of hospice enrollment, patients are asked whether they would potentially want antibiotics. This is little information regarding which patients are more likely to receive these antibiotics or the impact on comfort or longevity. To help guide discussions with patients and families and target future stewardship interventions, we sought to characterize the use of antibiotics in the outpatient hospice setting. Methods We performed a retrospective review of patients enrolled in hospice with the Mayo Clinic Health System -Midwest from 1/1/2017 through 1/1/2023. For those with documented Hospice Qualifying Condition (HQC), we assessed age at enrollment, gender, survival time (ST), and Charleston Comorbidity Index (CCI). We documented which antibiotics were prescribed and compared the rate of prescription based on the above characteristics. Results We identified 6452 patients with identifiable HQC. Of these, 1281 patients (19.8%) received 4173 antibiotic prescriptions. After removing refilled prescriptions, there were 2037 new prescriptions. Cephalosporins were the most common class of antibiotics prescribed (24.4% of antibiotics prescribed), followed by fluoroquinolones (19.9%), penicillin derivatives (14.4%), and trimethoprim (10.4%) (fig 1). Pulmonary (28.6%) and GI (31.9%) HQCs were most likely to receive antibiotics, neurologic was least likely (fig 2). There was no difference of age for those receiving antibiotics (80.6 yr) vs those not receiving (80.3 yr [p=0.53]), or for gender (male vs female OR 0.97 [0.86-1.10). CCI was higher in those patients who received antibiotics (4.3) than those not receiving (3.93, p< 0.001). Patients were more likely to receive antibiotics the longer they survived on hospice (4.7% surviving < 7d, 47.7% surviving >6mo – fig 3). Conclusion Antibiotics are an important pharmaceutical tool in the hospice setting. Nearly 20% of patients in hospice will receive antibiotics during their hospice course, with higher chance in those surviving longer periods and those enrolled for GI or pulmonary reasons. Discussions of antibiotic are crucial for these groups, and antimicrobial steward efforts should consider focusing on these patients. Disclosures All Authors: No reported disclosures

Abstract Background Plasma microbial cell-free DNA (mcfDNA) sequencing, commercially available from Karius® (Redwood City, CA), has been increasingly utilized in diagnosing endovascular infections. The 2023 updated Duke criteria incorporated detection of pathogen via metagenomic sequencing in its microbiologic criteria. We analyzed the clinical impact of mcfDNA sequencing in the diagnosis and treatment of suspected infective endocarditis (IE) cases. Methods We performed retrospective review of patients with suspected IE who underwent Karius® test at Mayo Clinic, MN, between 2017 to 2023. Results We preformed preliminary analysis of 25 patients. Analysis of baseline characteristics (table 1) revealed that these patients had significant predisposing factors for IE. Before accounting for mcfDNA sequencing, 3 (12%) met criteria for definite IE, 10 (40%) met criteria for possible IE, and 12 (48%) were rejected per 2023 Duke criteria. After incorporating mcfDNA sequencing result, 1 patient who was classified as possible IE was escalated to definite IE. This patient had previous infection of implantable cardioverter-defibrillator (ICD) with Streptococcus dysgalactiae. ICD was removed. She had development of endophthalmitis and stroke, 1 week and 2 weeks after the completion of IV antibiotics, respectively, with echocardiogram showing new tricuspid valve vegetation. Routine work-up was negative despite that she was not on any systemic antibiotics at the time of blood culture collection. mcfDNA sequencing detected Streptococcus dysgalactiae, making definite diagnosis of IE, leading to the physician’s decision to extend the IV antibiotic treatment (treatment escalation). Overall, after mcfDNA sequencing result, treatment decision was not impacted in 14 (56%), ongoing treatment was escalated in 4 (16%), de-escalated in 5 (20%), and antimicrobials was newly initiated in 2 (8%) (figure 1). Positive mcfDNA sequencing result often led to treatment escalation or initiation; negative result often led to treatment de-escalation (figure 2). Conclusion In challenging cases of suspected IE, mcfDNA sequencing led to alteration of antimicrobial treatment in 44% of cases. Further data collection and final analysis will include larger number of patients. Disclosures All Authors: No reported disclosures

Abstract Background Prolonged and recurrent fevers in pediatric outpatients often require specialist consultations, presenting a challenge in accurately triaging to the correct pediatric subspecialty. This study aims to develop an artificial intelligence (AI)-based model to accurately direct pediatric patients to appropriate subspecialties.Table 1.Patient characteristics and the department confirming the final diagnosis Table 1. Patient characteristics and the department confirming the final diagnosis Methods A retrospective study was conducted at the Mayo Clinic, Rochester, from December 1, 2020, to January 1, 2023, involving pediatric patients aged 0 to 18 referred for recurrent fever or fever of unknown origin. Six machine learning models, including gradient boosting, random forest, support vector machines (SVM), k-Nearest Neighbor (KNN), logistic regression (LR) and decision tree, were developed using 7 variables (demographics, chief complaints, referral sources, departments of same-day initial visit, and lab tests results within 30 days before initial visits). Data were extracted from external electronic health records (EHR) using Mayo Data Explorer and Lab Information Management Systems. Precision, Recall, F1 Score, and area under the curve (AUROC) were selected to measure the performance.Table 2.Performance of six machine learning models Table 2. Performance of six machine learning models Results The study evaluated 87 pediatric patients with a median age of 10.2 years (IQR: 4.6-13.8), including 43 (49%) females (Table 1). External provider referrals were noted in 40 (46%) patients. Musculoskeletal pain was the most common chief complaint, identified in 29 (33%) patients, in addition to prolonged or recurrent fever. Infectious disease and rheumatology divisions jointly saw 43 (49%) patients during the initial visit. Sub-optimal performance was observed in six machine learning models (Table 2). The random forest model showed the best results (Accuracy=0.39, Precision=0.34, Recall=0.39, F1 Score=0.35, AUROC=0.60) (Figure).Figure.ROC curves for various models Figure. ROC curves for various models Conclusion This study demonstrates the potential of AI-based models for outpatient triage prediction in pediatric patients with recurrent fever, using EHR data to optimize health resource utilization. This data serves as the groundwork to expand and refine this AI triage tool. Disclosures All Authors: No reported disclosures

Abstract Background The COVID-19 pandemic has underscored challenges with patient adherence to medical directives, particularly vaccine acceptance. While sociodemographic factors have been linked to non-COVID-19 vaccine hesitancy, the relationships between patient experience, the COVID-19 pandemic, and adherence to routine vaccinations are uncertain.Figure 1:Yearly influenza vaccine refusal, influenza vaccine administrations, and overall patient satisfaction since establishing care with a primary care provider from 2017-2023.Panel A (Influenza Refusals): the number of vaccine refusals among individuals who are Intermittently Vaccinated and Never Vaccinated for seasonal influenza since establishing care with a primary care provider over time.Panel B (Influenza Vaccinations): the number of vaccines administered over time since establishing care with a primary care provider among those who are Always Vaccinated and Intermittently Vaccinated for seasonal influenza.Panel C (Overall Satisfaction): the number of patients who indicated that they were maximally satisfied with their overall care following any interaction with the healthcare system over time. Methods We retrospectively analyzed influenza vaccination records of adult primary care patients in Olmsted County, Minnesota. Vaccination history was examined during two phases: Pre-Pandemic (1/1/2017—2/28/2020) and Pandemic-Plus (3/1/2020—12/31/2023). Vaccination status was defined as “always vaccinated” (AV), “never vaccinated” (NV), or “intermittently missed years of vaccinations” (IV) for seasonal influenza. Patient dissatisfaction was determined if patients negatively ranked their overall quality of care on standard patient experience surveys. We explored the relationship between influenza vaccination rates, healthcare engagement, and patient satisfaction.Figure 2:Multinomial logistic regression of patient satisfaction on vaccination status across the phases of the COVID-19 Pandemic, adjusted for engagement in the health care system, participation, and area of deprivation index (ADI) for patients that were (A) intermittently vaccinated compared to always vaccinated and (B) never vaccinated comparted to always vaccinated. The “Pre-pandemic phase” refers to influenza immunization data and patient satisfaction data prior to March 2020. The “Pandemic-plus phase” refers to immunization data and patient satisfaction data from March 2020 to January 2024. Low ADI ranking refers to areas with a low level of deprivation, whereas high ADI ranking refers to areas with a high level of deprivation. Individuals were considered low if they came from an area with a state ADI ranking from 1 to 5 and were considered high if they came from an area with a state ADI ranking from 6 to 10. Results From 1/1/2017 to 12/31/2023, 21% of individuals were AV (n=36,632), 52% were IV (n=90,776), and 27% were NV (n=46,418) for seasonal influenza. Post-pandemic onset, 7% (n=3,556) of the Pre-Pandemic AV and 32% (n=16,710) of the Pre-Pandemic IV never received another influenza vaccine. In the Pandemic-Plus phase, the IV and NV had a higher likelihood of disengagement with the healthcare system [odds ratio (OR) (95% CI): 1.59 (1.55, 1.64); 4.21 (4.09, 4.33)], residing in areas of greater deprivation [1.58 (1.53, 1.62); 1.99 (1.94, 2.05)], and self-identifying their race as Black [2.29 (2.09, 2.51); 3.29 (3.01, 3.60)] compared to the AV. After adjusting for healthcare engagement and area of deprivation, dissatisfaction OR increased from 1.03 (0.99,1.07) Pre-Pandemic to 1.07 (1.03,1.12) in the Pandemic-Plus phase among IV compared to AV. Similarly, the OR of dissatisfaction rose from 1.11 (1.05, 1.18) Pre-Pandemic to 1.16 (1.09, 1.24) in the Pandemic-Plus phase among those who were NV compared to those AV. Conclusion Higher healthcare dissatisfaction was observed among those inconsistently adherent to vaccination recommendations. Targeted efforts to enhance patient satisfaction may boost vaccination rates. Disclosures All Authors: No reported disclosures

Abstract Background Blastomyces is a dimorphic fungus found in the soil and is endemic to regions of the Ohio River basin and Southeastern United States. It can cause both local and systemic infections in several organs regardless of immunity status. Infection occurs through inhalation of aerosolized conidia. Blastomycoses most commonly affects the lungs and infection of the central nervous system (CNS) is rarely found representing approximately 5-10% of individuals with extra-pulmonary blastomycosis. Demographics of Patients with CNS Blastomycosis Methods Given the limited information on this rare form of blastomycoses, a retrospective review was conducted at a major tertiary center in Minnesota of adult inpatients diagnosed with proven or probable CNS blastomycoses between 2005 and 2020. Institutional Review Board approval at the Mayo Clinic was obtained. Data pertaining to diagnostic evaluation, treatment and outcomes were collected from eight medical charts found to meet criteria for proven or probable CNS Blastomycosis. Diagnosis, Treatment, and Outcomes in Patients with CNS Blastomycosis Results As seen in prior studies, most patients were male. The most common CNS related symptom on presentation was headache. Frequent comorbidities included diabetes, COPD, and alcohol use. Findings on MRI varied greatly. Blastomyces serum antibody was positive in only half of patients and urine antigen was frequently negative, however this test was not performed in one patient in this study. All but one patient survived to at least one year post diagnosis. All patients were treated with liposomal amphotericin B ranging from nine days to six weeks and voriconazole was the most frequently used azole. All patients treated with voriconazole survived at least one year following completion of treatment. Diagnosis, Treatment, and Outcomes in Patients with CNS Blastomycosis (continued) Conclusion This study emphasizes the importance of having a high suspicion when CNS symptoms are present in a patient with evidence of Blastomyces. Additionally, patients can have proven CNS blastomycoses without Blastomyces positive antibodies and/or antigen in blood or urine as well as variable MRI findings. Laboratory and Culture Results in Patients Found to Have CNS Blastomyces Disclosures All Authors: No reported disclosures

Abstract Background Intestinal colonization with carbapenem-resistant organisms (CRO) may be considered to inform empiric antibiotic selection for symptomatic infection. However, it is unclear how often gut colonizing CRE isolates are related to bloodstream isolates in hospitalized patients with bacteremia, especially in areas with high CRO prevalence. Minimum spanning tree of isolate relatedness Isolates and corresponding patient number (P1-P6) and rectal (R) or blood (B) specimen are noted within circles and allelic differences are numerated on linking lines between the circles. Group 1 and 3 isolates are possibly related to each other. Created with BioRender.com. Methods Patients with paired K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates cultured from surveillance rectal specimens and clinically collected blood specimens collected within 1-8 days of each other between 2019-2023 were identified at 3 Greek hospitals. Isolates were frozen and shipped to a reference laboratory in the U.S for whole genome sequencing (WGS) using Illumina MiSeq. Assembly and core genome multilocus sequence typing (cgMLST) analysis were performed with Ridom SeqSphere+ software. Isolate relatedness was based on the total number of allelic differences between each isolate: < 15, related; 16-50, possibly related; ≥ 51, unrelated. Results One hundred eight paired isolates were identified from 54 unique patients; 6 pairs and 12 total isolates underwent cgMLST. In 5 of 6 pairs (83%), the rectal isolate was collected prior to the bloodstream isolate. Rectal and bloodstream isolates were related to one another in 5 of 6 (83%) pairs and were unrelated in 1 pair. Two pairs collected from 2 distinct patients admitted to the same intensive care unit (patients 2 and 3, Figure) were possibly related (16-50 allelic differences) to each other. Conclusion In this pilot evaluation conducted in a setting of high CRO prevalence, KPC-producing K. pneumoniae isolated from paired rectal and blood specimens from individual patients were often related to each other, suggesting that intestinal colonization by this organism could inform empiric antibiotic treatment for bacteremia. Two patients from the same hospital unit had isolates that were possibly related, suggesting within hospital transmission. WGS is a powerful tool that can inform clinical and infection control practices. WGS of the remaining K. pneumoniae pairs and additional Acinetobacter baumannii pairs is ongoing. Disclosures Robin Patel, MD, I already disclosed so please pull from disclosure for other abstracts: Advisor/Consultant|I already disclosed so please pull from disclosure for other abstracts: Grant/Research Support|I already disclosed so please pull from disclosure for other abstracts: Honoraria

Abstract Background The opioid crisis and the increasing prevalence of multi-drug resistant organism (MDRO) infections pose a threat to public health. Opioid Use Disorder (OUD) patient are prone to MDRO colonization and infections, thus potentially leading to adverse outcomes during periods of critical illness. Understanding the prevalence and predictors of MDRO infections within this vulnerable population is critical to improving patient outcomes by optimizing interventions and treatment plans. Methods We conducted a retrospective, multicenter, cohort study to evaluate the prevalence of MDRO isolation among adults with OUD admitted to an intensive care unit (ICU) with an infection across four Mayo Clinic regions. Patients were classified to the MDRO cohort if an MDRO was isolated from standard cultures or rapid diagnostic testing within 48 hours of admission. We utilized descriptive statistics, univariate and multivariate least absolute shrinkage and selection operator (LASSO) regression analysis including random effect to account for site variability, to analyze demographic data, clinical characteristics, and outcomes. Results 790 critically ill adult OUD patients with infection-related admission were included in the study cohort. The prevalence of MDRO isolation was 22.5% (n=178), with MRSA being the predominant isolated MDRO. In LASSO regression analyses, we identified homelessness (OR: 1.79, p = 0.022), no Medications for OUD (MOUD) treatment (OR: 1.56, p=0.023), and positive Hepatitis C Virus (HCV) status (OR: 2.19, p = 0.012) as significant predictors for isolation of an MDRO. Intravenous (IV) antibiotic use in the preceding 90 days was also positively associated (OR: 1.04 per 24 hours, p = 0.007), alongside mental health disorders (OR: 2.03, p < 0.001) and diabetes (OR: 1.54, p = 0.023). Conclusion The high prevalence of MDRO isolation in critically ill OUD patients with infection is associated with complex social and clinical factors. Disclosures All Authors: No reported disclosures