Stevens, Ryan W W

Abstract Background Candidemia can occur as a consequence of gastrointestinal (GI) injury. The mortality of candidemia is high, ranging 30-60%, even with treatment with antifungal agents. In this retrospective matched case-control study, we aimed to elucidate the medical and surgical risk factors of developing candidemia in patients who received emergency surgery for GI ischemia and/or perforation, and compare clinical outcomes in these patients with or without candidemia. Methods All patients ≥ 18 years of age who had emergency GI surgery at Mayo Clinic Rochester, MN, for the indication of GI ischemia and/or perforation between 01/01/2018 to 07/31/2024 were included. Cases were defined as patients who developed candidemia during index admission and had no alternative sources of candidemia. Controls and cases were matched 4:1 on age (± 5 years), Charlson Comorbidity Index (± 3), and year of surgery (± 2 years). The relationships between risk factors of interest and case/control were assessed using conditional logistic regression. Results Among medical risk factors, any shock requiring vasopressor (OR = 3.44, 95% CI 1.00, 11.97) or respiratory failure (OR = 8.20, 95% CI 1.04, 64.53) during hospitalization were associated with increased risk of candidemia. Among surgical risk factors, perforation in the upper GI tract was strongly associated with development of candidemia (OR = 16.99, 95% CI 2.11, 136.95) and perforation in the lower GI tract were less likely to lead to candidemia (OR = 0.06, 95% CI 0.01, 0.44). The patients who had diffuse intraabdominal contamination were more likely to develop candidemia compared to those who had no contamination or contained contamination (OR = 3.87, 95% CI 1.33, 11.25). The patients with candidemia showed signal towards higher in-hospital and 30-day mortality, and had significantly longer stay in the hospital. Conclusion Candidemia was more frequently identified in patients with shock, respiratory failure, upper GI perforation, and intra-abdominal contamination, and contributed to significant morbidity and mortality. Further analysis will include building a multivariate logistic regression model to implement prospective trial for early initiation of antifungal therapy for high-risk population. Disclosures All Authors: No reported disclosures

Abstract Background Outpatient parenteral antimicrobial therapy (OPAT) is effective and cost-efficient, but 12%–63% of patients experience adverse events, requiring close monitoring. Therapeutic drug monitoring (TDM) is routinely used for vancomycin and aminoglycosides but is underutilized for beta-lactams (BLs) due to limited access, logistical barriers, and clinician inexperience. This study evaluated its use and clinical impact within a high-volume OPAT program. Methods This retrospective, single-center cohort included adult patients (≥18 years) enrolled in an OPAT program who received cefepime (CEF), piperacillin/tazobactam (TZP), or meropenem (MEN) and underwent BL TDM between April 2023 and April 2025. BL TDM was not protocolized within the OPAT program; however, institutional guidance supported its use in carefully selected patients. We aimed to describe TDM indications, lab trends, microbiological profiles, and the impact of TDM on treatment. Results During the study period, 25 OPAT patients underwent BL TDM. TDM was performed in patients receiving CEF (64%), TZP (20%), and MEN (16%). The most common indication for TDM was suspected beta-lactam toxicity (32%) (Figure 1). Post-TDM therapy adjustments were made in 52% (n = 13), including changes in dosing frequency (38.5%) and dosage strength (30.8%). Additional changes included infusion strategy modification or agent substitution (15.4% each). Subtherapeutic levels were the most common reason for adjustment (46.2%), followed by adverse effects, supratherapeutic levels, and changes in renal function (23.1% each). Skin, soft tissue, and musculoskeletal infections were most common (Figure 2). Positive cultures were present in 80%, with Pseudomonas spp most frequently isolated. Therapy was completed in 17 patients; 7 discontinued early, and 1 had treatment ongoing. Reasons for therapy discontinuation are detailed in Table 1. Conclusion BL TDM is contributing to a paradigm shift in OPAT practice by improving both efficacy and safety. While inpatient TDM typically targets efficacy, safety concerns more commonly motivate TDM in the OPAT setting. Although this review involved a small cohort, our experience adds to the growing body of evidence supporting BL TDM as a tool to enhance patient outcomes in the OPAT setting. Disclosures All Authors: No reported disclosures

Abstract Background According to consensus guidelines, area under the concentration–time curve (AUC) is recommended for vancomycin dosing rather than trough-based monitoring, but transition to AUC-based dosing requires substantial staff education and resource allocation. We sought to evaluate the level of congruency between vancomycin total daily doses (TDD) determined using a trough concentration goal of 10-15 mcg/mL compared with an online Bayesian calculator targeting an AUC of 400-600 mg·h/L.Patient DemographicsInitial Dose Results Methods We performed a retrospective, multicenter cohort study of vancomycin therapeutic drug monitoring (TDM) in non–critically ill adults hospitalized from March 1, 2017-December 31, 2021. Patients were included if they received intravenous vancomycin for ≥72 hours with a documented trough target of 10 to 15 mg/L, had ≥1 serum vancomycin trough concentration assessed at steady state, and received ≥2 doses of vancomycin after serum assessment with or without dose adjustment. Using an online vancomycin calculator with Bayesian modeling, the study team input patients’ trough-based dosing data to retrospectively estimate the initial vancomycin AUC exposure achieved and the initial and post-trough TDD recommended for an AUC target of 400 to 600 mg⸱h/L. The initial and post-trough vancomycin total daily dose (TDD) derived by the online calculator were compared with the actual doses used for each patient when a trough concentration of 10 to 15 mg/L was targeted.Comparison of Trough-Based and AUC-Based Dosing of Vancomycin AUC indicates area under the concentration–time curve; TDD, total daily dose. Dashed line indicates where the 2 methods are equal; shading indicates where the 2 methods are within 20% of each other Results In total, 89 patients were included in the study. The actual vancomycin TDD with trough monitoring (target, 10-15 mg/L) was within 20% of the recommended AUC-based TDD for 62 patients (70%) with initial dosing and for 74 (83%) after the initial trough concentration. Nephrotoxicity was rarely observed (2%) and the median duration of vancomycin was 4 days. Conclusion Given the frequency of dosing similarity between 400-600 mg·h/L AUC and 10-15 mg/L trough-based dosing, vancomycin trough-based monitoring to a goal of 10-15 mg/L is an option warranting further exploration. Disclosures All Authors: No reported disclosures

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 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 Methicillin-susceptible Staphylococcus aureus bacteremia (MS-SAB) is treated with antistaphylococcal penicillins (ASP) or cefazolin. Altered pharmacokinetics in the setting of hypoalbuminemia may reduce the likelihood of therapeutic success in patients receiving highly protein bound beta-lactams. ASPs and cefazolin are 94% and 80% protein bound, respectively. We assessed the impact of hypoalbuminemia (≤2.5 g/dL) on clinical outcomes in patients with MS-SAB treated with ASPs or cefazolin.Table 1:Unweighted and weighted analysis of full cohort by albumin statusTable 2:Weighted analysis of cefazolin and ASP cohorts by albumin status Methods This single center, retrospective study included adults (≥18 years) admitted with community-acquired MS-SAB between 1/1/2006 and 12/31/2019 who received ASPs or cefazolin and had a serum albumin obtained between the date of first culture positivity and 72 hours of definitive therapy. Exclusion criteria included receipt of ≥5 days of MSSA active empiric therapy prior to definitive, polymicrobial bacteremia, antibiotics for an indication other than MS-SAB, or central nervous system infection. The primary outcome was failure to clear blood cultures within 72 hours of definitive therapy initiation. Propensity score weighting was used to adjust for baseline differences between cohorts. Results 160 patients were included with 61 (38.1%) being hypoalbuminemic (Table 1). In the propensity score weighted analysis, the primary outcome occurred in 37% of patients with an albumin ≤2.5 g/dL vs. 10.2% with an albumin >2.5 g/dL (p< 0.001). This finding was consistent in both ASP and cefazolin subgroups (Table 2). Hospital length of stay was longer in hypoalbuminemic patients but did not represent a statistically significant difference in the weighted overall analysis (15.9 vs. 11.6 days, p=0.8). There was no difference in inpatient mortality in any of the cohorts analyzed. 90-day all-cause mortality was higher in hypoalbuminemic patients only in the cefazolin subgroup analysis (20.7% vs 4.9%, p=0.019). Conclusion The presence of hypoalbuminemia was associated with failure to clear blood cultures within 72 hours of definitive therapy initiation in patients with MS-SAB. While no significant difference in mortality was observed overall, the higher mortality in the cefazolin subgroup warrants further research on the impact of hypoalbuminemia on clinical outcomes in patients with MS-SAB. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).

Abstract Background Despite effective therapy for methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia with anti-staphylococcal penicillins (ASP; e.g., oxacillin, nafcillin) or cefazolin, persistent bacteremia is associated with poorer clinical outcomes and increased complications. Emerging strategies, such as combination therapy with an ASP or cefazolin and ertapenem, have demonstrated the potential to accelerate microbiologic clearance in persistent MSSA bacteremia. However, despite its increasing utilization in clinical practice, data on the effectiveness of this combination regimen remains limited. We sought to describe the clinical characteristics and outcomes of patients with MSSA bacteremia receiving combination therapy. Methods We performed a single-center, retrospective study of adult patients with MSSA bacteremia who received ASP or cefazolin and ertapenem combination therapy from 2019-2023. Time to blood culture clearance, in-hospital mortality, and 90-day relapse were examined. Results A total of 57 patients were included: median age of 65 years [IQR 53-73] with 75.4% male. MSSA bacteremia complicated by infective endocarditis and cardiac implantable electronic device infection occurred in 35.1% and 12.3%, respectively. The median length-of-stay was 16 days [IQR 12-28], and 57.9% required ICU admission. Forty (70.2%) patients underwent source control interventions such as valve replacement, device extraction or surgical debridement. The median duration of bacteremia prior to combination therapy initiation was 4 days [IQR 3-6]. Blood culture clearance occurred in a median of 1 day. The median duration of combination therapy was 4 days [IQR 3-6]. In-hospital mortality was 15.8%. None of the patients surviving the hospitalization experienced relapsed bacteremia within 90 days. Conclusion This study supports growing evidence that combination therapy may offer benefits in managing persistent MSSA bacteremia, specifically with regards to time to blood culture clearance. Further investigation is warranted to determine optimal timing of combination therapy and if known benefits of combination therapy translate into superior clinical outcomes as compared to monotherapy. Disclosures All Authors: No reported disclosures

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

Abstract Background Optimizing antimicrobial prescribing for urinary tract infections (UTI) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, ambulatory antibiotic order panel for UTI was implemented in the Mayo Clinic Enterprise on 5/16/2022. The order panel provides antimicrobial regimens which align with both institutional and national treatment guidelines based on patient comorbidities, complicating factors, and beta-lactam allergy status. We aimed to assess the impact of panel use on antibiotic prescribing for complicated and uncomplicated cystitis in the ambulatory setting. Methods This retrospective review included ambulatory encounters from the Mayo Clinic Enterprise in 2022 and 2023. Eligible encounters were randomly selected and included those with a primary ICD-10 code of cystitis performed by primary care or urgent care clinicians. Encounters were excluded if patients had symptoms indicative of pyelonephritis, underwent urinary instrumentation within 30 days, or had a urinary pathogen isolated within 90 days. The primary outcome was concordance with institutional guidelines. Secondary outcomes included repeat healthcare contact and therapy duration. Outcomes were analyzed with Pearson's chi-squared and Wilcoxon rank sum tests (α level = 0.05). Results 793 encounters (397 panel vs. 396 non-panel) were included. Prescribing was guideline concordant in 79.3% and 64.9% (p< 0.001) of panel and non-panel encounters, respectively. Inappropriate duration was the most common reason for non-concordance in the panel use cohort. There was no difference between groups for repeat healthcare contact incidence. Antimicrobials prescribed differed between panel and no-panel groups (Table 1), with higher use of sulfamethoxazole/trimethoprim and lower use of cefdinir in the panel cohort. Numerically shorter durations were seen in the panel group, with more 3- and 5-day regimens than the no-panel group. Conclusion Use of a pre-populated antimicrobial order panel for outpatient cystitis encounters resulted in greater adherence to institutional guideline recommendations, particularly in terms of antimicrobial selection, without adversely impacting repeat healthcare contact. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

Abstract Background Optimizing antimicrobial regimens for outpatients with community-acquired pneumonia (CAP) represents an area of opportunity for ambulatory antimicrobial stewardship programs. A pre-populated, antibiotic order panel for outpatient respiratory syndromes was implemented in the Mayo Clinic Enterprise on 1/4/2021. For CAP, it provides national guideline adherent regimens (i.e., selection, dosing, and durations) by patient comorbidity and beta-lactam allergy status. We aimed to assess impacts of panel use on antibiotic prescribing in outpatients with CAP. Methods This retrospective review included Mayo Clinic outpatient encounters from Minnesota in 2021 and 2022. Eligible encounters used a CAP-related primary ICD-10 code, conveyed intention to treat CAP in encounter notes, and were performed by primary care, emergency department, or urgent care clinicians who managed ≥1 CAP patient with the panel and ≥1 without the panel during the study period. Encounters were excluded if patients were already receiving antibiotics at the time of encounter. The primary outcome was adherence (drug and duration) to guideline recommendations. Secondary outcomes included utilization rate by agent and therapy duration. Outcomes were analyzed with Kruskal-Wallis rank sum and Pearson’s chi-squared tests (α level = 0.05). Results 352 encounters (134 panel vs. 218 non-panel) were included. Prescribing was guideline adherent in 61.9% and 29.4% (p< 0.01) of panel and non-panel encounters, respectively. The most common reason for guideline non-adherence during panel use was inappropriate drug selection (n = 45/51, 88.2%). This was predominantly driven by use of the incorrect section of the treatment panel based on patient comorbidity status (n = 30/45, 66.7%). Individual antibiotic utilization rates differed between panel and non-panel cohorts (Table 1), with higher rates of amoxicillin and amoxicillin/clavulanate use and lower rates of azithromycin and doxycycline use in the panel cohort. Durations >5 days were more common in the non-panel as compared to the panel cohort (34.4% vs. 7.5%, p < 0.01). Conclusion Use of a pre-populated antimicrobial order panel in outpatients with CAP resulted in greater adherence to national guideline recommendations. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun: Grant/Research Support|Cidara: Grant/Research Support|Scynexis: Grant/Research Support