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Abstract Background Catheter related bloodstream infections (CRBSI) are associated with increased resource use, treatment costs, and mortality among patients with cancer. Coagulase-negative staphylococci (CoNS) are the most common cause of central venous catheter (CVC) infection in this population. While CVC removal remains the gold standard, CRBSI with CoNS is sometimes managed with CVC salvage, despite incomplete safety and efficacy data in patients with hematological malignancy.Table 1.Baseline Demographic and Clinical DataTable 2.Baseline Characteristics by Treatment Strategy Methods A retrospective review was conducted of adult patients at Mayo Clinic Rochester from 2013 to 2024 diagnosed with hematological malignancy and CRBSI with CoNS. Patients were included in a “CVC removed” group if the line was removed within 5 days of bacteremia onset, and all others were included in a “CVC retained” group. Electronic medical records were evaluated for relevant clinical comorbidities, risk factors, and management. The primary outcomes of interest were 90-day mortality and relapse. To control for baseline differences between groups, we employed a propensity weighted analysis based on inverse probability of treatment weighting using the propensity score.Weighted cumulative event rates for Relapse and Mortality Results A total of 140 cases were included, of whom 95 (67.9%) had undergone BMT and 111 (80.4%) were neutropenic at time of CRBSI. The predominant CoNS identified was Staphylococcus epidermidis (88.6%). 79 (56.4%) patients had the CVC retained and 61 (43.6%) underwent CVC removal. Those in whom the CVC was retained were more likely to be BMT recipients (p=0.007). However, line removal was more common with PICC lines (p< 0.001) and in those hospitalized for management of line-associated bacteremia (p=0.022). Within 90 days, there were 10 patients (cumulative incidence 8.2%) who had microbiological relapse (2 [4.3%] in the CVC removed group and 8 [11.1%] in the CVC retained group). Propensity weighted analysis demonstrated significantly higher rate of microbiologic relapse with CVC retention (p=0.043) but no difference in mortality (p=0.128), as shown by weighted cumulative event rate curves in Figure 1. Conclusion Despite the finding of increased risk of relapse associated with CVC retention, there was no significant difference in mortality between CVC removal and retention among individuals with CoNS CRBSI and hematological malignancy. Disclosures All Authors: No reported disclosures

Abstract Background Staphylococcus aureus is a challenging pathogen which causes a multiplicity of human diseases around the globe, acquired in the community and healthcare settings alike. Treatment of S. aureus infection can be challenging and is further compromised by antimicrobial resistance. Understanding of its pathogenesis, transmission pathways and the dynamics of its genome evolution and associated adaptations is incomplete. One strategy to assess genome evolution is to assess codon bias. Historically, studies have focused on the consequences of coding changes; assessing silent mutations in the form of synonymous codon usage bias represents a novel approach to studying genetic adaptation.Figure 1.Principal component analysis (PCA) (A) and sPLS-DA (B) separate S. aureus from complex mates.sPLS-DA component 1 relies on a hypothetical protein, identified here by its NCTC 8325 genomic coordinates, as important for separating S. aureus from complex mates (C). Methods Here, the codon bias of 2,872 genes was queried against all publicly available complete S. aureus plasmids and genomes. Using public BioSample data, genomes were sorted by disease state (e.g., bacteremia, pulmonary infection) and geographical collection site. Results Isolates from Nairobi, Kenya were most different from other isolates, suggesting that geographical isolation may shape codon bias signature. In addition, codon bias of two MSCRAMM proteins implicated in human disease - SdrC and FnBPB - varied between isolation sources, suggesting a role for codon bias in S. aureus genetic adaptation to selective pressures of infection. Additionally, codon bias out-performed coding and nucleic acid mutational metrics in separating members of the S. aureus complex, S. aureus, Staphylococcus argenteus, Staphylococcus schweitzeri, and Staphylococcus roterodami; Fig 1, sparse partial least squares analysis (sPLS-DA) mean AUC codon: 0.89762, nucleic acid: 0.82266, codon bias: 0.9996 (relying on hypothetical protein NC_007795.1:516850-517419). Conclusion This analysis suggests that codon bias in S. aureus is a source of genetic adaptation that can be used to separate strains by geographical isolation source, and separate S. aureus sensu stricto from other S. aureus complex members. Disclosures Nicholas Bedard, MD, Stryker: Advisor/Consultant 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 In 2019, the US performed 290,000 breast reconstructions with an estimated infection rate of 3-35%. Tissue expander infections detract from desired aesthetic effects, delay adjuvant treatments, increase morbidity and mortality, and have high recurrence rates (20-40%). Little is known about risk factors for recurrent tissue expander infections, particularly the impacts of different treatment modalities. Methods We conducted a single-center retrospective cohort study of adult women post-mastectomy who developed microbiologically-proven tissue expander infection between the period of 2017 – 2024. Outcomes including 12-month infection recurrence and risk factors for recurrence were compared between surgical versus nonoperative groups, as well as between three surgical strategies (i.e., one-stage, two-stage, explantation). Unadjusted and adjusted logistic regression models were used to assess the associations between the treatment modalities and the outcomes. Univariate models assessed the relationship between the covariates of interest and infection recurrence. Results 107 patients were included, with the majority treated with combination of antibiotics and surgical therapy (Table 1). There was no significant difference in outcomes when the operative versus antibiotics alone cohorts were compared (Table 2). The odds of infection recurrence and rehospitalization in patients who underwent two-staged exchange or explantation were significantly lower when compared with the one-staged group (Table 3). Univariate modeling found severity and radiation therapy to be numerically more common in the group experiencing recurrence, with a trend towards statistical significance (Table 4). Conclusion Our study demonstrates reduced risk of recurrent tissue expander infection with two-staged exchange or explantation, compared to one-staged exchange. Though limited by small sample size, the strengths of our study include our presentation of the real-world variability of these syndromes and their management, adjustment for infection severity and other potential confounders; and the focus on microbiologically-defined infections. Disclosures All Authors: No reported disclosures

Abstract Background The COVID-19 pandemic saw a worrisome rise in mucormycosis cases in India, especially among those receiving corticosteroid therapy. While corticosteroids are essential for managing severe COVID-19 cases, their immunosuppressive action appears to augment infection risk. Clinically, prolonged steroid use may result in severe forms of mucormycosis; however, this requires rigorous systematic evaluation. Methods We conducted an exhaustive analysis of 327 mucormycosis cases and 596 COVID-19 controls, all of whom were treated during the second wave in India. Exposure to steroids was carefully categorized by duration into three groups: short-term (1-5 days), standard-term (5-10 days), and long-term ( > 10 days). Each case was biopsy-proven, with further radiographic confirmation of disease extent. Special emphasis was laid on intracranial extension as a marker of severity, along with tracking treatment outcomes and survival. Statistical modeling was used to correct for important confounders, including diabetes status, glycemic control, and concurrent use of other immunomodulators. Results The results were striking. Those receiving steroid treatment for more than ten days of duration had a nearly fourfold higher incidence of intracranial mucormycosis compared with short-term-treated patients (38.2% vs. 12.5%, p< 0.001). Each day of steroid use accounted for a 12% increase in associated risk. While mortality rates were equal, patients receiving prolonged treatment had a considerably increased number of surgical procedures (35.3% vs. 16.7%, p=0.02) as well as more complicated hospitalization. Those with diabetes were especially sensitive to such effects of prolonged treatment. Conclusion The study highlights the role of cautious use of corticosteroids in the management of COVID-19. Our work gives strong evidence for the importance of compliance with guideline-based recommendations for corticosteroid duration, especially for high-risk populations. This study empowers healthcare practitioners with unequivocal evidence to provide optimal COVID-19 treatments while avoiding the risk of severe fungal infection. Disclosures All Authors: No reported disclosures

Abstract Background Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behavior and results in sub satisfactory concentrations. Limited evidence suggests that the posaconazole oral delayed-release (DR) tablets may be crushed. Methods This was a retrospective cohort study of hospitalized adults who received EFT administration of posaconazole IR suspension or crushed DR tablets between 2018 and 2024. Patients were eligible if they had at least one serum concentration drawn ≥5 days after posaconazole initiation. The primary outcome was the attainment of therapeutic (≥700ng/mL for prophylaxis, ≥1,000ng/mL for treatment) serum concentration within 30 days. Secondary outcomes included time to therapeutic serum concentration, adverse drug effects, and frequency of clogged EFT. Multivariable cox proportional hazards regression was used to assess the relationship between posaconazole formulation and attainment of therapeutic concentrations while adjusting for confounding variables. Results Of the included patients, 100 received DR tablets and 48 received IR suspension. There were no significant differences in baseline characteristics or severity of illness. Among DR tablet and IR suspension recipients, 59% and 23% achieved therapeutic concentrations, respectively (p < 0.001). After adjusting for age, sex, BMI, drug interactions, posaconazole indication, malabsorptive gastrointestinal conditions, IR suspension was significantly less likely than crushed DR tablets to achieve therapeutic posaconazole concentrations within 30-days (HR 0.37, 95% CI 0.20-0.71; p < 0.003). The crushed DR tablet group required less total daily posaconazole to achieve therapeutic concentrations (400 vs 600 mg/day, p = 0.003). Clogged EFTs were more frequent in the crushed DR tablet group (27% vs 10%, p = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalemia. Conclusion Administration of crushed posaconazole DR tablets via EFT is more likely to attain therapeutic concentrations compared to IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation. Disclosures Patrick M. Wieruszewski, PharmD, FCCM, Wolters Kluwer/UpToDate: Advisor/Consultant

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