Cole, Kristin

Abstract Objectives To describe and compare anorectal manometry findings in constipated adolescents with and without dyssynergic defecation (DD). Methods We retrospectively reviewed adolescents ≤18 years who underwent anorectal manometry (ARM) and/or balloon expulsion testing (BET) between 2015 and 2022. Patients with prior pelvic floor therapy, inflammatory bowel disease, or colon surgery were excluded. DD was defined by abnormal ARM (paradoxical anal contraction or inadequate anal relaxation ≤20% during simulated evacuation) and/or abnormal BET (>60 s). Manometric parameters were compared between patients with and without DD and between those with abnormal versus normal BET. Diagnostic performance of rectoanal pressure gradient cutoffs were assessed. Results A total of 170 adolescents were included; 69 (40.6%) met criteria for DD. Median age was 17 years (interquartile range [IQR] 16–18), and 80.7% were female. Gastrointestinal symptoms did not differ between groups. Patients with DD demonstrated significantly more negative rectoanal pressure gradients compared with those without DD (median [IQR]: −49.0 mmHg [−73.9 to −31.4] vs. −25.2 mmHg [−40.2 to −9.8]; p < 0.001). Rectal sensory thresholds did not differ significantly between groups. A rectoanal pressure gradient cutoff of −45 mmHg demonstrated the best balance of sensitivity (58%) and specificity (86%) for identifying DD. Depression was more prevalent among adolescents with DD ( p = 0.007). Conclusions Rectoanal pressure gradient is a useful manometric parameter for identifying DD in constipated adolescents, particularly when BET is unavailable. Psychological factors such as depression may be more prevalent in this population.

ABSTRACT Clinical pharmacists are increasingly recognized as vital contributors to acute stroke care, yet their role remains inconsistently defined and underutilized across health care systems. This consensus statement explores the expanding presence of clinical pharmacists within interdisciplinary stroke teams, particularly in the management of both acute ischemic stroke ( AIS ) and hemorrhagic stroke. This consensus statement panel was composed of clinical pharmacists, emergency medicine physicians, and a vascular neurologist. The Grading of Recommendations, Assessment, Development, and Evaluation ( GRADE ) approach was used to assess the level of certainty and strength of recommendations. We focused on two questions regarding the clinical pharmacist's role in caring for adult patients presenting to the emergency department ( ED ) with AIS or hemorrhagic stroke. Despite the very low level of evidence, a consensus was reached for the following recommendations: (1) clinical pharmacist involvement in AIS care for adult patients presenting to the ED and (2) clinical pharmacist involvement in hemorrhagic stroke care for adult patients presenting to the ED . Based on the available literature, we believe optimizing the clinical pharmacist role is a critical factor in improving time‐sensitive treatment and equity in care delivery.

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 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 &lt; 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 &lt; 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 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 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 &gt;2.5 g/dL (p&lt; 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).