Ilges, Dan

Abstract Education and allergy referral via nurse-driven online messaging to patients (n = 1,284) with penicillin allergy labels (PALs) reduced PALs by 8.6%. The percentage decrease of “unknown” (14.8%) and “rash” (7.9%) PALs were higher vs “hives” (6.1%) and “itching” (1.4%) reaction types.

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 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 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 Posaconazole immediate release (IR) suspension is the standard product for enteral feeding tube (EFT) administration but has erratic pharmacokinetic behaviour, often resulting in subtherapeutic concentrations. Limited evidence suggests that 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 drug concentration drawn ≥5 days after posaconazole initiation. The primary outcome was attainment of therapeutic drug concentrations. Secondary outcomes included time to therapeutic serum concentration, adverse drug events, and frequency of occluded EFT. Results Of the included patients, 48 received IR suspension and 100 received DR tablets. Baseline characteristics and severity of illnesses were well balanced. Among IR suspension and crushed DR tablet recipients, 39% and 80% achieved therapeutic concentrations, respectively (P = 0.002). After adjusting for age, sex, BMI, drug interactions, posaconazole indication and malabsorptive conditions, crushed DR tablets were significantly more likely than IR suspension to achieve therapeutic posaconazole concentrations within 30 days (HR 5.22, 95% CI 2.35–11.61). Occluded EFTs were more frequent among crushed DR tablet recipients (27% versus 10%, P = 0.022), while no differences were observed in the occurrence of hepatotoxicity or hypokalaemia. Conclusions With EFT administration, crushed posaconazole DR tablets were associated with a greater likelihood of achieving therapeutic concentrations compared with IR suspension. The optimal technique for administering crushed DR tablets to prevent EFT complications warrants investigation.

Abstract Antimicrobial use among hospital-at-home (HaH) patients across three Mayo Clinic sites was evaluated from 2023 to 2024. Nearly three-quarters of patients were administered an antibiotic during HaH admission. Ceftriaxone was the most commonly used antibiotic and respiratory infections were the most common antimicrobial indication. Further investigation into stewardship opportunities is warranted.

ABSTRACT Carbapenem‐resistant Acinetobacter baumannii (CRAB) are difficult‐to‐treat pathogens that primarily cause health care‐associated infections. Sulbactam/durlobactam (SUL/DUR) is a novel antibiotic combination that is uniquely formulated to target CRAB isolates. However, investigations of SUL/DUR's pharmacokinetics in obese patients are limited. Here, we report on the successful treatment of CRAB bacteremia in a patient with acute renal failure and severe obesity (weight 273 kg, body mass index 103 kg/m 2 ) with SUL/DUR and meropenem combination therapy. The patient had a calculated creatinine clearance of 25 mL/min and received therapy with intravenous SUL/DUR 1 g/1 g every 8 h over 3 h in combination with intravenous meropenem 500 mg every 8 h to complete 14 days of therapy. Pharmacokinetic analysis revealed target attainment with prolonged half‐life ( T 1/2 ) and volume of distribution (Vd) of 35.3 h and 81.3 L for sulbactam and 30.5 h and 169.1 L for durlobactam, respectively. Susceptibility testing using the broth disk elution test did not show synergy between SUL/DUR and meropenem. No adverse effects were observed, and the patient achieved clinical cure without recurrence of A. baumannii infection.