58. Impact of Order-set Modifications and Provider Education on Broad-Spectrum Antibiotic Use in Patients Admitted with Community Acquired Pneumonia

Abstract Background Following updates to IDSA guidelines in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for prescribing of broad-spectrum antimicrobial therapy. The objective of the study was to evaluate changes in broad-spectrum antibiotic days of therapy (DOT) following these order-set updates with accompanying provider education. Methods This was a multi-center, quasi-experimental, retrospective study of patients with CAP from 9/1/19 to 10/31/19 (pre-intervention) and 9/1/20 to 10/31/20 (post-intervention). Patients were identified using ICD-10 codes indicating lower respiratory tract infection and excluded if had a positive SARS-COV-2 PCR during admission. Data collected included demographics, labs and vitals, radiographic, microbiological, and antibiotic data. The primary outcome was change in broad-spectrum antibiotic DOT, specifically anti-pseudomonal β-lactams and anti-MRSA antibiotics. Secondary outcomes included guideline-concordance of initial antibiotics, utilization of an order-set to prescribe antibiotics, and length of stay (LOS). Results A total of 331 and 352 patients were included in the pre- and post-intervention groups, respectively. The overall duration of broad-spectrum therapy was a median of 2 days (IQR 0-8 days) in the pre-intervention period and 0 days (IQR 0-4 days) in the post-intervention period (p< 0.001). Patients in whom the order-set was used in the post-intervention period were more likely to have guideline-concordant regimens ([36/40] 90% vs. [190/312] 60.9%; p = 0.003). There were no differences in order set usage (10% vs. 11.3%, p = 0.642) between the pre- and post-intervention groups, respectively. Hospital LOS was lower in the post-intervention cohort (4.8 days [2.9-7.2 days] vs. 5.3 days [IQR 3.5-8.5 days], p = .002). Conclusion Despite low utilization of the order-set, education surrounding order-set changes appeared to improve antibiotic prescribing and hospital LOS in our population. Further opportunities to improve order-set use and thus further increase guideline-concordant therapy are still available. Disclosures Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator) David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.)


High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose
Background. Trimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX.
Methods. IRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and > 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium < 135 mmol/L, hyperkalemia with potassium > 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed.
Results. Each group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received >1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2. Background. A regional antibiotic stewardship program (ASP) within a large integrated healthcare system covering two, non-academic, tertiary care medical centers and an additional six community hospitals implemented multiple interventions to optimize antimicrobial therapy and reduce unnecessary hospital costs, such as transition to extended-infusion (EI) piperacillin/tazobactam (TZP), formulary restriction of antimicrobials, and antimicrobial stewardship clinical review. The purpose of this study was to evaluate the cost savings associated with these regional ASP initiatives.
Methods. This was a multicenter, retrospective, observational review of regional stewardship interventions across eight inpatient medical centers in Oregon. Data was collected from January 2019 to December of 2020. Cost savings associated with reduced TZP administrations was based on the duration of therapy for each encounter in adults who received TZP for >24 hours in 2020. The regional antimicrobial restriction policy was implemented in February 2020. Cost savings attributed to antimicrobial formulary restrictions and reduction in overall days of therapy/1000 patient days (DOT) were based on EPIC costs.
Results. The reduction in number of administrations with implementation of EI TZP resulted in $226,420 saved in 2020. $182,837 was saved due to decreased usage of restricted antimicrobial agents. An additional $433,341 was saved for overall antimicrobial costs due to 19,775 days reduction in overall DOT/1000 patient days.

Conclusion.
A community-based regional ASP has resulted in substantial financial impact and identified areas for future cost savings within the region. Background. A significant proportion of inpatients labeled with penicillin allergies do not have a true IgE-mediated hypersensitivity, which may unnecessarily limit options for treatment of infection and lead to suboptimal antibiotic selection. Postacute care settings may provide a unique opportunity to capture patients at risk for adverse outcomes related to penicillin allergy labels. The objective of the study was to assess the feasibility and impact of a penicillin delabeling program in an inpatient rehab setting.
Methods. We conducted a prospective observational study. Inpatients with penicillin allergies were identified weekly by manual review of electronic medical records. A clinical pharmacist reviewed each patient's chart and identified patients for inclusion. Patients were excluded if they had a history of IgE-mediated hypersensitivity to penicillin within last 5 years, a history of a non-IgE mediated hypersensitivity, were severely immunocompromised, or were prescribed a contraindicated medication.
Results. A total of 72 charts were reviewed over nine months, and 37 (51.4%) had their penicillin allergy updated to reflect prior beta-lactam tolerance. Of the 72 patient that were evaluated, 28 (38.9%) were eligible for potential penicillin allergy delabeling, and 44 (61.1%) were ineligible. 59 (81.9%) of the patients had a moderate-high risk allergy, 12 (16.6%) had a low risk allergy, and 1 (1.4%) had an intolerance. Of the 28 eligible patients, 11 (39.3%) had their allergy removed, 13 (46.4%) deferred testing, and 4 (14.2%) could not be tested due to staffing. Of the 28 patients that had their allergy delabeled, 7 (21.4%) had their allergy removed by MAR review, 2 (7.2%) had a skin test with a negative result, and 2 (7.2%) had a direct oral challenge with a negative result.
Conclusion. A penicillin allergy delabeling program using a collaborative physician-pharmacist team model efficiently removed reported allergies in post-acute care patients. The post-acute care setting is an opportune environment to conduct a penicillin allergy delabeling program for patients not currently needing acute medical treatment.
Disclosures. Background. Penicillin (PCN) allergies are reported in up to 10% patients and are associated with adverse clinical and antimicrobial stewardship outcomes. Here we describe a multidisciplinary quality improvement (QI) initiative to facilitate PCN delabeling at a large urban hospital.
Methods. Starting in August 2020, the departments of Allergy and Infectious Diseases (ID) began a joint QI effort to employ a part time allergist nurse practitioner (ANP) for PCN allergy assessment and delabeling. The ANP used a daily system generated list to identify and assess adult patients with PCN allergy and contact teams to request a consult. An ID fellow also assisted with identifying patients and contacting care teams. The ANP then offered skin/oral PCN challenge or direct label removal based on history after discussion with an allergist physician. Baseline, clinical, and allergy characteristics were compared between patients delabeled and not delabeled using Chi-square and Mann-Whitney U test. Primary endpoints were antibiotic utilization outcomes from index admission post ANP assessment to 30-days post discharge. Secondary endpoints included readmission, length of stay (LOS), mortality, and sustained removal of the PCN allergy at 30-days.