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Abstract Background Beta-lactam pharmacokinetics can be significantly altered in patients with malignancy. Therapeutic drug monitoring (TDM; i.e., drug level testing) may facilitate pharmacokinetic/pharmacodynamic (PK/PD) target attainment, but the data are limited. This study aimed to characterize PK/PD target attainment of anti-pseudomonal beta-lactams in hematology/oncology patients.Table 1:Case DescriptionGraph 1:Distribution of Beta-Lactam TDM Indications Methods We conducted a retrospective review of beta-lactam TDM performed between June 2022 and June 2024 in hospitalized adults with hematologic or solid organ malignancies. We included patients who underwent beta-lactam TDM during clinical care, typically for extracorporeal membrane oxygenation (ECMO), extremes of body weight, suspected augmented renal clearance, multidrug-resistant infection, or suspected dose-dependent beta-lactam toxicity. Primary outcomes were (1) the proportion achieving target beta-lactam concentrations and (2) the proportion undergoing antibiotic dose adjustment based on TDM results.Table 2:Institutional Dosing Guidelines Results There were 47 TDM episodes in 20 unique patients. Considering only the first TDM per patient, 10 (50%) patients achieved target concentrations, 2 (10%) were below target, and 6 (30%) were above target. Antibiotic dose adjustments were made in 8 (40%) patients in response to TDM results. The most common indication for beta-lactam TDM was concerns regarding accurate renal clearance, followed by extremes of weight. Conclusion Retrospective findings suggest that beta-lactam TDM facilitated individualization of therapy in 40% of patients with either hematological or solid organ malignancy, with dose adjustments often intended to improve antibiotic safety. Future studies should refine the criteria for beta-lactam TDM use in this population and determine the need for tailored PK/PD targets in patients with impaired host response to infection. Disclosures All Authors: No reported disclosures

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAb) is a multi-drug resistant, opportunistic pathogen. Colistin is one of a few remaining treatment options, but resistance exists globally. Methods Between 2017 and 2019, 551 CRAb isolates were collected through the international Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen (SNAP). Demographics, clinical characteristics, mortality, and a desirability of outcome ranking (DOOR) measure combining lack of clinical response, unsuccessful discharge, renal failure, and C. difficile infection, were recorded for each patient. A central laboratory measured colistin minimum inhibitory concentrations (MICs), and each isolate was classified as colistin-intermediate (MIC ≤2µg/mL) or resistant (MIC ≥4µg/mL). All isolates were sequenced on the Illumina platform, and the genomes were used to construct a phylogenetic tree and assess for variants within known colistin resistance-related genes. Results 18% of the 551 isolates were colistin-resistant. Compared to patients with colistin-intermediate isolates, patients with resistant strains were more likely to have been admitted from a healthcare facility, but otherwise had similar demographics and Charlson comorbidity indices. Focusing on patients with bloodstream or respiratory infections (n=217) uncovered increased 30-day mortality in patients with monomicrobial, colistin-resistant infections (11/19, p=0.008) when compared to monomicrobial-intermediate (41/102), polymicrobial-resistant (4/20) and polymicrobial-intermediate infections (18/76). Comparative genomics indicated that the majority of isolates belonged to clonal complex 2 (CC2), and that colistin resistance concentrated in certain genetic lineages. Variant analysis uncovered nonsynonymous mutations near and within the histidine kinase domain of pmrB, part of the PmrAB two-component system that regulates lipopolysaccharide modifications which can alter colistin susceptibility. Conclusion In this global cohort, patients with monomicrobial, colistin-resistant CRAb infections had increased mortality. New treatment options are needed for multidrug-resistant CRAb, and this study provides further evidence that pmrB may serve as a worthwhile drug development target. Disclosures Madison Stellfox, MD, PhD, Cumberland Pharmaceuticals: Grant/Research Support Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria David van Duin, MD, PhD, British Society for Antimicrobial Chemotherapy: Editor stipend|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant Yohei Doi, MD, PHD, GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria

Abstract Background Phage therapy has gained increasing interest as an approach to treat antimicrobial- resistant bacterial infections. Standardized, reproducible PST methods are needed to rapidly identify active phages for potential clinical use. Here, PST of 24 clinical isolates of carbapenem-resistant K. pneumoniae (CR-Kp) to 6 K. pneumoniae phages (3 from KlebPhaCol and 3 from phage hunting) was assessed using a plaque assay (PA) and a liquid assay (LA), and results compared. Phage Susceptibility Testing: Agreement Between Plaque Assay and Liquid Assay Methods For the PA, 2µL of 10−1-10−8 phage dilutions were spotted on bacterial laws of CR-Kp (double agar overlay), and plaques scored upon overnight incubation at 37°C [0 (no activity), 1+ (lysis from without), 2+ (concentration-dependent lysis), 3+ (clear plaques, small or medium size), 4+ (clear plaques of large size); scores ≥ 2+ were considered susceptible]. Testing was performed on 3 different days. If ≥ 2 replicates scored ≥ 2+, the result was classified as susceptible. For the LA, phages and bacteria were combined (MOI=10) in 96-well plates [phage-bacteria combinations (3 replicates), phage controls (106 PFU/mL), bacterial controls (BC, 105 CFU/mL), media sterility controls] and plates incubated at 37°C for 24h, with OD600 measured every 15 min. Hold time (HT) — delay in achieving inflection at the beginning of exponential growth phase — was calculated for phage-treated compared to BC wells. Testing was performed on 2 different days. Mean HT was computed for each phage-bacteria combination and results assessed as susceptible or not using cutoff HTs of 4h and 8h. Results Using a LA HT cutoff of 4h, there was complete agreement with results of the PA for 3 phages, and 96, 79 and 67% overall agreement for 3 other phages (Table). Using a LA HT cutoff of 8h, there was complete negative agreement for 4 phages, but lower overall agreement between the LA and PA (58-96%). Increased classification as susceptible by PA compared to LA was the main source of disagreement when using a LA HT cutoff of 8h. Conclusion Here, two PST assays were compared, and greater agreement was found when using a 4h compared to an 8h HT LA cutoff. These results represent a step forward in the standardization of PST methods, bearing in mind that correlation of results with pre-clinical and clinical outcomes is needed. Disclosures Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection: a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication, a patent on PET imaging of bacterial infection|MicuRx Pharmaceuticals and bioMérieux: Grant/Research Support|PhAST, Day Zero Diagnostics, DEEPULL DIAGNOSTICS, S.L., Nostics, HealthTrackRx, bioMérieux and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course: Honoraria

Abstract Background Catheter-associated urinary tract infection (CAUTI) is one of the most prevalent nosocomial infection reported and is associated with significant resource expenditure across health care facilities. Methods We conducted a retrospective review of newly catheterized patients at a tertiary hospital over 12-months period. Demographic, clinical, and diagnostic data were collected. Based on the National Health Safety Network (NHSN) criteria, patients were divided into two groups: health care associated infection (HAI) and criteria not met (CNM). Outcome measures included secondary bloodstream infections, hospital re-admission, death, and microbiological relapse at 30 days of hospital discharge. These outcomes were compared between groups. Results A total of 314 patients were identified, of whom 55 (17.5%) met the criteria for HAI. Demographic, clinical and microbiological data are summarized in Tables 1-3. In comparison to the CNM group, the HAI group showed higher rates of fever, urinary frequency, bladder pain or tenderness, costovertebral angle tenderness, positive blood cultures, growth of urinary microorganisms >100,000 colony forming units (CFU), and imaging evidence of infection (p< 0.01). Blood stream infections were observed in 20 (6.6%) patients, with 12 of these in the HAI group, and were attributed to a urinary source in 7 cases. Composite outcomes were affected by fever (p< 0.01), imaging evidence of infection (p< 0.01) and presence of renal abscess, whereas the age of catheter, dysuria, bladder tenderness, urinary frequency, urinary CFU threshold didn't achieve statistical significance. After adjusting for the Charlson Comorbidity Index, the HAI group showed higher rates of re-occurrence of blood stream infections, re-admission and mortality within 30 days (Table 4). Conclusion Fever, imaging evidence of infection, and renal abscess were significant predictors of adverse composite outcomes, whereas catheter age, dysuria, bladder tenderness, urinary frequency, and urinary CFU threshold were not. Refinement of the NHSN surveillance definition of CAUTI may enhance targeted resource allocation for prevention efforts. Disclosures All Authors: No reported disclosures

Abstract Background Fecal microbiota, live-jslm (RBL) is FDA-approved for prevention of recurrent Clostridioides difficile infection (rCDI) in adults following completion of antibiotic treatment. The safety and efficacy of RBL have been demonstrated in trials, but few studies have evaluated outcomes in real-world populations. The primary objective of ROAR (NCT05835219) is to assess RBL effectiveness in reducing rCDI through 8 weeks in clinical practice. Table 1. Treatment success rates by subgroup Methods ROAR is an ongoing, prospective, multicenter, open-label, non-interventional registry of patients receiving RBL for rCDI prevention in the United States. Adults who completed antibiotics for rCDI and are not in an interventional trial are eligible. The primary endpoint assesses the proportion of patients who experience treatment success (no CDI recurrence through 8 weeks). Other objectives describe rCDI management in real-world clinical practice and adverse events (AEs) after RBL administration. This analysis includes patients who received RBL within 30 days of completing antibiotics for rCDI. Results As of September 18, 2024, 76 patients received RBL within 30 days of completing antibiotics and completed 8 weeks of follow-up. Patients were mostly White (93.4%) and female (76.3%), with a median age of 69 years (range, 19-96 years) and a median body mass index of 24.4 (range, 16.5-49.4). Through 8 weeks, 82.9% of patients (63/76; 95% CI, 72.5%-90.6%) experienced treatment success. Similarly, the rate of treatment success was 87.8% (36/41) in the subgroup of patients who received RBL after an antibiotic washout period > 72 hours. Treatment success rates ranged from 77-100% across patient subgroups, including those stratified by age and number of previous CDI episodes within the past 3 years (Table). Overall, 18 (23.7%) patients experienced an AE, 6 (7.9%) experienced a serious AE, and 1 (1.3%) experienced an AE of special interest (large bowel obstruction). AEs assessed as related to RBL occurred in 3 patients (3.9%). There was 1 fatal AE during the study, considered unrelated to RBL. Conclusion Initial results from ROAR are consistent with previous RBL trial results, indicating that RBL is effective and safe for preventing rCDI through 8 weeks after administration in real-world practice. Disclosures Nicholas W. Van Hise, PharmD, Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant Teena Chopra, MD, MPH, Cepheid: Advisor/Consultant|Ferring Pharmaceuticals, Inc: Advisor/Consultant|Melinta: Speaker|Pfizer: Advisor/Consultant|Pfizer: Speaker|Shinogi: Speaker Kelly R. Reveles, PharmD, PhD, AstraZeneca: Advisor/Consultant|Ferring Pharmaceuticals: Advisor/Consultant Sahil Khanna, MBBS, MS, Ferring Pharmaceuticals, Inc: Grant/Research Support|ProbioTech Inc: Advisor/Consultant|Rise: Advisor/Consultant|Takeda: Advisor/Consultant|Vedanta: Grant/Research Support Lasse Nielsen, MS, Ferring: Employee Lorien E. Urban, PhD, Ferring Pharmaceuticals Inc: Employee

Abstract Background Handshake antimicrobial stewardship (HAS) is an effective stewardship approach characterized by regular, face-to-face interactions with antimicrobial prescribers and broad review of all active antimicrobials. Benefits of this approach include enhanced relationship building and opportunities for targeted education. We conducted a mixed methods study to evaluate the impact of once-weekly HAS rounds among Hospital Internal Medicine (HIM) teams in an academic medical center. Methods An infectious diseases (ID) physician and pharmacist conducted weekly table rounds with a HIM teaching team consisting of a hospitalist, advanced practice providers (APPs), APP fellow(s), and sometimes medical students. All patients on antimicrobials and without an active ID consult were reviewed and recommendations were provided. Thereafter, the stewardship team solicited ad hoc questions from other HIM teams via walking rounds in their offices. The number, type, and acceptance rate of recommendations were collected prospectively. A survey was sent to all HIM providers to obtain feedback on HAS rounds. Results HAS rounds were conducted weekly from February 7, 2024, to February 19, 2025, with a total of 52 sessions. Over the study period, 340 recommendations were provided, and 314 recommendations were implemented, yielding a recommendation implementation rate of 92.4%. The most common recommendation types were antimicrobial discontinuation (n=76, 22.4%), duration modification (n=63, 18.5%), and de-escalation (n=39, 11.5%). The survey was sent to 102 HIM providers and completed by 19 for a response rate of 18.6%. All respondents stated HAS added value or greatly added value to their practice. Antimicrobial selection (n=16, 84.2%), de-escalation (n=12, 63.2%), and pharmacy expertise (n=6, 31.6%) were areas in which providers saw the greatest benefit. Eighteen providers (94.7%) recommended expansion of HAS to non-HIM services. Conclusion Targeted, once-weekly HAS rounds resulted in high-yield interventions that were frequently accepted and perceived as highly valuable by HIM providers. Once-weekly or intermittent HAS practices might be considered in practice settings where resources or logistical constraints limit broader, hospital-wide handshake stewardship practices. Disclosures All Authors: No reported disclosures

Abstract Background Antimicrobial stewardship programs (ASP) commonly employ formulary restriction and prospective audit with feedback; however, frontline prescribers and other unit-based clinicians may enhance core ASP tactics as ASP extenders. We hypothesized that unit-based pharmacists act as ASP extenders and sought to characterize ASP interventions in their routine work.Top individual antimicrobial classes intervened on by unit-based pharmacistsUnit-based pharmacist antimicrobial intervention types Methods Retrospective, observational study of ASP interventions by unit-based pharmacists from July 2017 - April 2025 across the Mayo Clinic Enterprise. ASP interventions recorded using a standardized pharmacist documentation tool (Epic iVents [Software]) were collected retrospectively. Interventions on hospitalized, adult patients categorized as ‘ASP’ or linked with an antimicrobial were included; interventions by ASP dedicated staff were excluded. Secondary outcomes included: intervention subtypes and outcomes, location, and associated antimicrobial(s). Frequencies and percentages were used to summarize categorical data. Results A total of 104,055 interventions were included from 59,106 unique patients at 26 hospitals with the majority performed at the three destination sites. On average, 1,107 interventions were completed monthly by unit-based pharmacists. Frequently targeted antimicrobial classes were vancomycin and derivatives, penicillins, and 3rd/4th-generation cephalosporins (e.g., ceftriaxone and cefepime) (Figure 1); 20,111 (19.3%) interventions were on ≥ 1 antimicrobial. Of the 66,827 interventions with a documented subtype, ASP was the most common (77.8%), with the remainder classified as dose (17.3%), medication (3%), or duration changes (1%) (Figure 2). A minority (2.2%) were documented as conducted under pharmacist collaborative practice agreements. Documented prescriber intervention rejections were uncommon (6.6%). Reported outcomes, when available, included therapy optimization, cost savings and avoidance of adverse drug events. Conclusion Unit-based pharmacists acted frequently as ASP extenders. These findings support unit-based pharmacist and ASP collaborative efforts. Disclosures All Authors: No reported disclosures

Abstract Aim To assess the long‐term efficacy of vagus nerve stimulation (VNS) in Dravet syndrome and identify key factors influencing treatment response. Method We conducted a two‐center, retrospective cohort study of 15 patients (six females, nine males; median age at seizure onset 4 months [range 2–12 months]) with Dravet syndrome who underwent VNS implantation. Seizure frequency was evaluated over 12 months and up to 10 years after implantation. Linear mixed‐effects regression was used to analyze the impact of antiseizure medications (ASMs) and VNS parameters on seizure outcomes. Results A 50% or greater reduction in seizure frequency was observed in 93.3% (14 of 15) of patients at 12 months and 86.7% (13 of 15) of patients across the 10‐year follow‐up. This seizure reduction was independent of ASM use; the VNS duty cycle was a significant predictor of seizure reduction. Two individuals (13.3%) experienced minor adverse events. Interpretation VNS provides durable seizure reduction in Dravet syndrome, independent of ASM adjustments. These findings highlight the importance of early VNS initiation and parameter optimization in managing genetically defined epilepsy syndromes.

Abstract Background Hematopoietic stem cell transplant (HSCT) recipients are susceptible to infections with respiratory viruses resulting in higher morbidity and mortality. Parainfluenza virus (PIV) infection in the setting of leukopenia is associated with higher risk of lower respiratory tract infection and mortality. Intravenous immunoglobulin (IVIG) has been used as adjunctive treatment in viral respiratory infections, although data guiding its use is limited.Table 1:Patient CharacteristicsTable 2:Clinical Outcomes Methods We conducted a retrospective cohort study of adult HSCT recipients diagnosed with PIV infection at our institution from January 2014 to September 2024. Diagnosis of PIV infection was made via BioFire® Respiratory Panel multiplex polymerase chain reaction (PCR) or viral culture from nasopharyngeal or bronchoalveolar lavage. Data on clinical characteristics and outcomes were collected and reviewed.Table 3:Clinical Outcomes for Patients with IgG <767 mg/dL Results A total of 110 HSCT recipients were diagnosed with PIV infection by PCR or viral culture within the study period. Patient characteristics and clinical outcomes are summarized in Tables 1 and 2. PIV type 3 was the most common, followed by PIV type 4 and type 1. Eighteen patients (16.36%) had co-infections with another virus. A total of 16 patients received IVIG at time of PIV infection. The mean cumulative IVIG dose was 28.75 grams. Patients who received IVIG were more likely to have been hospitalized due to symptoms related to the viral infection (p=0.03) and had a lower immunoglobulin G level (p< 0.001). Overall, there was no significant difference in rates of mechanical ventilation (12.5% vs 7.45%, p=0.616), development of secondary fungal or bacterial infection (12.5% vs 12.7%, p=1), or 90-day mortality (18.75% vs 6.38%, p=0.123) among patients treated with or without IVIG, respectively. Similarly, in a subset analysis of patients with IgG level < 767 mg/dL, there were no significant difference in outcomes for patients treated with or without IVIG (Table 3). Conclusion There were no significant differences in clinical outcomes, including rates of mechanical ventilation, secondary infections, or 90-day mortality, between HSCT patients who received IVIG and those who did not for PIV infection. Larger studies are needed to gain insight into efficacy of IVIG as adjunctive treatment in PIV infections in this population. Disclosures All Authors: No reported disclosures

Abstract Background Lyme arthritis is a manifestation of disseminated infection with Borrelia spp., typically presenting as knee monoarthritis weeks to months after infection. Most patients respond to antibiotics, but some develop antibiotic-refractory Lyme arthritis (ARLA), characterized by proliferative or autoimmune synovitis despite clearance of active infection, with proposed risk factors including treatment delay, host genetics, and intra-articular steroid use prior to antibiotics. Table 1 Characteristics of cohort. IQR = interquartile range, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, WBC = white blood cell. Table 2 Comparison of characteristics and outcomes between ARLA and non-ARLA patients Methods We performed a retrospective chart review of adult patients with Lyme PCR-positive synovial fluid at our center between 01/2004 and 02/2025. ARLA was defined as persistent inflammatory arthritis despite ≥8 weeks of antibiotics and/or negative repeat PCR after antibiotics. Statistical analysis was done on R and STATA. Figure 1 Type of antibiotics administered during the first course (A) and the second course (B) Figure 2 Box plot comparing the median time from symptom onset and treatment initiation in patients who had complete symptomatic resolution with any duration of antibiotic therapy, and those that did not have symptomatic resolution with antibiotic therapy. Results Table 1 summarizes the characteristics of the study cohort. Definitive Lyme arthritis was diagnosed in 67 patients. Of these, 35 patients (52%) achieved complete symptom resolution after one course of antibiotics, and 45 patients (67%) achieved resolution after up to two courses. Doxycycline was used as first-line therapy in 97% of cases (Figure 1). Antibiotic-refractory Lyme arthritis (ARLA) developed in 20 patients (30%); of these, 7 required disease-modifying antirheumatic drugs (DMARDs), and 3 underwent synovectomy. ARLA was associated with incomplete response to a single antibiotic course and persistent joint effusion on post-treatment radiography (Table 2). Intra-articular steroid use prior to antibiotic therapy was associated with a threefold increased odds of ARLA, although this did not reach statistical significance. Patients who responded to antibiotics had a shorter median time to treatment (19 days) compared to non-responders (42 days) (Figure 2). Conclusion In this cohort, 30% of patients were ultimately diagnosed with antibiotic-refractory Lyme arthritis (ARLA), a rate notably higher than the previously reported 10%. Despite advancements in Lyme disease diagnostics, we observed significant delays in diagnosis and initiation of appropriate antibiotic therapy, as well as the use of intra-articular steroids prior to antibiotics. These factors may contribute to the development of ARLA. Disclosures All Authors: No reported disclosures