A multifaceted stewardship intervention helps curb steroid overprescribing in hospitalized patients with acute exacerbations of COPD

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Corticosteroid overprescribing is well documented in real-world practice. There is currently no evidence to guide best practices for steroid stewardship. The aim of this study was to assess the effects of a 3-part stewardship intervention strategy on inpatient steroid prescribing in patients with acute exacerbations of COPD (AECOPD). Summary Investigators implemented a 3-part stewardship initiative consisting of (1) an anonymous survey for providers on steroid prescribing in a simplified case of AECOPD, (2) face-to-face education and review of survey results, and (3) prospective audit and feedback from a clinical pharmacist. This was a quasi-experimental before-and-after study evaluating hospitalized adults diagnosed with AECOPD in two 12-month study periods before (April 2019-March 2020) and after (May 2020-April 2021) implementation. The primary outcome was mean inpatient steroid dosing. Secondary outcomes were duration of therapy, length of stay (LOS), 30-day readmissions, 30-day mortality, and incidence of hyperglycemia. Per power analysis, there were 27 patients per cohort. The interventions resulted in a significant reduction in prednisone equivalents during hospitalization: 118 mg vs 53 mg (P = 0.0003). This decrease was similar in ICU (160 mg vs 61 mg, P = 0.008) and non-ICU (102 mg vs 49 mg, P = 0.004) locations. There was no significant difference in duration of therapy (8 days vs 7 days, P = 0.44), length of stay (3.3 days vs 3.9 days, P = 0.21), 30-day mortality (4% vs 7%, P = 0.55), 30-day readmissions (15% vs 7%, P = 0.39), or rate of hyperglycemia (48% vs 44%, P = 0.78). Conclusion A multifaceted stewardship intervention significantly reduced steroid dosing in hospitalized AECOPD patients. This reduction was not associated with known deleterious effects.

105. Fluoroquinolone Stewardship at a Community Health-System: A Decade in Review

Background Fluoroquinolone stewardship is a common target for antimicrobial stewardship programs seeking to maintain or improve fluoroquinolone susceptibility rates. Additional benefits include reducing C. difficile infection rates, drug toxicities, and resistance to other antimicrobials as fluoroquinolones can co-select for resistance. The Norton Healthcare antimicrobial stewardship program was founded in 2011 and provides services at 4 adult hospitals with ~1600 beds. Main fluoroquinolone stewardship activities have included provider education, prospective audit and feedback, and guideline and order-set development. The purpose of this study was to describe the resistance and usage rates of fluoroquinolones over time. Methods This was a descriptive study examining individual adult hospital antibiograms from 2010 to 2020. Levofloxacin susceptibility rates to E. coli and P. aeruginosa were collated from annual antibiograms between 2010 and 2020 for outpatients and each adult hospital. Adult hospital resistance rates were aggregated and weighted accordingly to number of isolates per hospital per year. Additionally, levofloxacin and ciprofloxacin inpatient days of therapy (DOT) was collected since 2016 when DOT was first readily retrievable and was normalized per 1000 patient days to compare between different time points. Results Outpatient levofloxacin likelihood of activity against P. aeruginosa improved from 81% to 91%. Outpatient levofloxacin likelihood of activity against E. coli remained stable between 84 – 86% (Figure 1). Adult inpatient fluoroquinolone usage decreased by approximately 75% from 83.5 to 21.37 DOT/1000 patient days since 2016 (Figure 2). Adult inpatient levofloxacin likelihood of activity against P. aeruginosa improved from 53% to 83%. Adult inpatient levofloxacin likelihood of activity against E. coli improved from 65% to 75% (Figure 3). Conclusion The Norton Healthcare antimicrobial stewardship program has been effective in reducing unnecessary fluoroquinolone usage and improving inpatient fluoroquinolone susceptibility rates. Future studies should examine opportunities to translate successes to the outpatient phase of care. Disclosures Ashley Wilde, PharmD, BCPS-AQ ID, Nothing to disclose Paul S. Schulz, MD, Gilead (Consultant, Speaker’s Bureau)Merck (Consultant, Speaker’s Bureau)

117. How Does Antimicrobial Stewardship Provider Role Affect Prospective Audit and Feedback Acceptance by the Attending Physician?

Background Antimicrobial stewardship (AMS) teams are commonly multidisciplinary. The effect of AMS provider role on prospective audit and feedback (PAF) acceptance has previously been investigated with mixed results. PAF of restricted antimicrobials (carbapenems, linezolid, daptomycin, and tigecycline) in adult inpatients at our large Canadian academic centre has been performed since 2018. Actionable feedback is communicated via chart note plus one of a phone call, direct message, or in-person discussion with the most responsible physician of the attending team in order to optimize the prescription if deemed necessary. The objective of this study was to assess the effect of AMS provider role on PAF acceptance. Methods A 3 year retrospective review of all PAF events was undertaken. All audited prescriptions were included. Logistic regression was used to determine odds ratios for acceptance for individual AMS provider roles of pharmacist, physician, and supervised post-graduate physician trainee. Results Out of 1896 prescriptions audited, actionable feedback was provided to the most responsible physician in 731 (39%) cases. 677/731 (93%) of audited antibiotics were carbapenems. The overall acceptance rate was 82% (598/731). Acceptance rate and odds of acceptance based on AMS provider role were as follows: pharmacist alone 171/208 (82%), OR 1.04, 95% CI 0.70-1.59, physician alone 141/160 (88%), OR 1.85, 95% CI 1.12-3.20, pharmacist-physician duo 211/268 (79%), OR 0.73, 95% CI 0.50-1.07, and supervised post-graduate physician trainee 75/95 (79%), OR 0.81, 95% CI 0.48-1.41. Conclusion The overall acceptance rate was high. There was a higher odds of acceptance if an AMS physician was providing PAF alone, highlighting the importance of physician involvement. Disclosures Dima Kabbani, MD, AVIR Pharma (Grant/Research Support, Other Financial or Material Support, Speaker)Edesa Biotech (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)

159. Characterization of Suboptimal Discharge Antimicrobial Prescriptions and Effect of Inpatient Audit and Feedback on Quality of Antimicrobial Prescribing

Background Approximately 30% of children are discharged from the hospital with an antimicrobial prescription; nearly a third of these prescriptions are suboptimal. Although the best approach to antimicrobial stewardship of discharge prescriptions remains uncertain, prospective audit and feedback (PAF) has improved inpatient antimicrobial use. We aimed to identify and characterize suboptimal discharge antimicrobial prescribing and assess the impact of inpatient PAF on the quality of discharge antimicrobial prescribing at a free-standing children’s hospital. Methods A retrospective review of enteral discharge antimicrobial prescriptions between 12/1/20-5/31/21 and parenteral antimicrobial prescriptions sent to our hospital’s infusion pharmacy between 3/1/21-5/31/21 was performed to determine if suboptimal or not. A prescription was determined to be suboptimal if the antimicrobial choice, dose, frequency, duration, formulation, or indication was not consistent with institutional and/or national guidelines. Data collection included the antimicrobial, indication, and prescribing medical service. Prescriptions were evaluated for a corresponding inpatient PAF for the same drug and indication and then stratified based on inpatient PAF completion. Results A total of 1192 discharge prescriptions for 698 unique patients over 834 hospital encounters were reviewed. Overall, 243 (20%) prescriptions were identified as suboptimal; reasons were duration (16%), dose (8%), frequency (5%), or antimicrobial choice, formulation, or route (≤1%). Prescriptions for cephalexin had the highest rate of suboptimal prescribing (80/167, 48%), followed by amoxicillin-clavulanate (89/203, 44%). A corresponding inpatient PAF was identified for 675 (57%) of discharge antimicrobial prescriptions. Inpatient PAF prior to discharge resulted in fewer suboptimal discharge prescriptions for the same antimicrobial (8% vs. 36%, p < 0.001). Conclusion Antimicrobial prescribing at inpatient discharge was suboptimal in 1 of every 5 prescriptions. Inpatient PAF was associated with improved antimicrobial prescribing at hospital discharge. Antimicrobial stewardship programs should continue to explore ways to capture and intervene on antimicrobials prescribed at discharge. Disclosures Hayden T. Schwenk, MD, MPH, Nothing to disclose

121. Evaluation of Multifaceted Antimicrobial Stewardship in Optimizing Antimicrobial Usage in Intraabdominal Infection at a Community Hospital

Background Treatment of intraabdominal infections (IAI) commonly involves broad spectrum antimicrobials based on the severity and etiology of infections as well as the underlying medical conditions. However, the overuse of broad-spectrum agents has driven selection for Gram-negative and -positive resistance, as well as collateral consequences such as Clostridioides difficile colitis. We sought to evaluate the utilization of a pharmacy-driven multifaceted antimicrobial stewardship (AMS) intervention to optimize empiric antimicrobial therapy by risk stratification among IAI patients and reduce the number of antibiotic treatment days. Methods This is a single-center case observation study in hospitalized adult IAI patients on antimicrobial therapy from Dec 2019-Feb 2020 compared to patients from Dec 2020-Feb 2021 after initiation of AMS with daily prospective audit and feedback. The composite primary outcome is reduction of antibiotic treatment days and de-escalation from broad spectrum antibiotics (fluoroquinolones, piperacillin/tazobactam, and carbapenems) to cephalosporins. Results We identified 40 patients each in the baseline (pre-AMS group) and post-AMS group via electronic medical record. Baseline characteristics were well-matched between groups. The majority of patients were diagnosed with community-acquired IAIs such as appendicitis, diverticulitis, and cholecystitis. Fluoroquinolone use as empiric therapy was significantly lower in the post-AMS group vs. pre-AMS group (2.5% vs. 25%, p< 0.001), while non-Pseudomonas cephalosporin use was increased (25% post-AMS vs. 0% pre-AMS, p< 0.001). Oral fluoroquinolone use at discharge was significantly decreased in the post-AMS group (p< 0.001). Antibiotic treatment days remained unchanged. There was no statistical difference between the two groups in 30-day mortality, 30-day readmission, relapse, and C. difficile colitis. Conclusion A multifaceted antimicrobial therapy intervention successfully reduced the use of fluoroquinolones in patients with community-acquired IAI during hospitalization and discharge. No differences in mortality, readmission, or relapse rates were observed. Disclosures All Authors: No reported disclosures

32. Impact of a Four-Year Antimicrobial Stewardship Program on Antimicrobial Resistance

Background Antimicrobial resistance (AMR) is an increasing threat to public health and antimicrobial consumption is a primary driver of resistance. Many studies have shown that the implementation of an antibiotic stewardship program (ASP) improves prescribing of antibiotics and can reduce AMR. Purpose of the study was to assess the impact of a successful ASP, implemented for four years, on AMR in our 427-bed tertiary general hospital. Methods We monitored pharmacy data for the years 2015 (pre-intervention) and 2016-2019 (post-intervention) for antibiotic consumption (DDD/100 bed-days) and resistance rates. AMR data were obtained from the clinical microbiology laboratory’s electronic database. To achieve the goals of ASP we used a range of interventions as pre-authorization strategy for the protected antibiotics (tigecycline, carbapenems, quinolones, glycopeptides, daptomycin, colistin, linezolid), prospective audit and feedback with direct intervention, de-escalation or switch from iv to oral administration and appropriate selection and duration of chemoprophylaxis in surgery. Results Significant reductions were observed for: total antibiotics, colistin, carbapenems, quinolones and tigecycline consumption during study period. Significantly lower resistance rates were documented in 2019 compared to 2015 for Pseudomonas aeruginosa and for Klebsiella pneumoniae. As for Acinetobacter baumannii isolates, which in our hospital are highly-resistant exhibiting >90% resistance to carbapenems, no significant changes were noted during the study period. Infections caused by Gram-positive pathogens are less prevalent in our hospital. Lower rates of vancomycin-resistant enterococci were noted after the implementation of our ASP (30.4% in 2019 vs. 50.0% in 2015 for E. faecium and 0.6% vs. 6% for E. faecalis, respectively), whereas methicillin-resistant S. aureus isolates increased (40% in 2019 vs. 31.1% in 2015), possibly because most of these infections were not hospital-acquired. Resistance rates of Pseudomonas and Klebsiella Conclusion Our ASP was successful in reducing antibiotic consumption and AMR for important pathogens. Disclosures All Authors: No reported disclosures

38. Impact of Antimicrobial Stewardship Interventions on Adherence to Clostridioides difficile Treatment Guidelines

Background Facility-specific treatment guidelines are a priority intervention recommended in the CDC Core Elements of Hospital Antimicrobial Stewardship Programs (ASPs). Our ASP sought to improve adherence to the facility C. difficile infection (CDI) treatment guideline by implementing prospective audit and feedback of CDI cases, changing fidaxomicin from being restricted to Infectious Diseases consult use, to only requiring prospective audit and feedback, and allowing fidaxomicin and oral vancomycin orders only through the order set. This study reviews the impact of these interventions. Methods This single-center retrospective quasi-experimental study evaluated inpatient CDI lab events 3 months pre-intervention (10/1/2019-12/31/2019) and post-intervention (10/14/2020-1/14/2021). Patient and treatment data was evaluated via chart review. The primary outcome was adherence to CDI treatment guideline. ASP intervention types were categorized. Statistical analyses were performed using Chi-squared or Fischer’s exact, where appropriate. Results Baseline characteristics were well matched between the 58 and 70 patients pre and post intervention respectively (Table 1). ASP interventions resulting from the prospective audit and feedback are described in Table 2 and overall acceptance rates were high (88%). Guideline adherence improved significantly from 71% pre to 90% post-intervention (p=0.005). Reasons for non-adherence included vancomycin dose incorrect for the severity of illness (9 pre vs 2 post), inappropriate duration (4 pre vs 0 post), use of combination therapy in non-fulminant disease (5 pre vs 3 post), and not using fidaxomicin for recurrent disease (3 pre vs 2 post). Clinical outcomes pre and post intervention were not different in this small sample size: colectomy 1 (2%) vs 1 (1%) p=1, 60 day all- cause mortality 15 (26%) vs 14 (20%) p=0.43, and CDI recurrence at day 60 9/43 (21%) vs 5/56 (9%) p=0.131. Conclusion A bundle of ASP interventions including prospective audit and feedback of CDI cases improved adherence to facility-specific CDI treatment guidelines. Disclosures Tamara Krekel, PharmD, BCPS, BCIDP, Merck (Speaker’s Bureau) Erik R. Dubberke, MD, MSPH, Ferring (Grant/Research Support)Merck (Consultant)Pfizer (Consultant, Grant/Research Support)Seres (Consultant)Summit (Consultant)

37. Impact of a Vancomycin/Piperacillin-tazobactam Audit and Feedback Program

Background Vancomycin and piperacillin-tazobactam (VPT) combination therapy is associated with nephrotoxicity and provides broad-spectrum coverage that may be unnecessary. We conducted a pre-post implementation study to assess the impact of an audit and feedback program for VPT at our academic medical center. Methods Automated alerts were used to identify patients on VPT at the University of Washington Medical Center (UWMC)-Montlake (ML) and UWMC-Seattle Cancer Care Alliance (SCCA) hospitals. Baseline data was collected on patients from 1/20/20-6/2/20: electronic medical records were reviewed for antibiotic indication, duration, renal function, and presence of Infectious Disease (ID) consult. From 6/25/20-10/31/20, all patients on combination therapy without an ID consult were reviewed by the antimicrobial stewardship programs at ML and SCCA, respectively. If intervention was warranted, the ML steward discussed the case with the provider then documented the conversation. The SCCA steward, instead, discussed the case with the team pharmacist. The primary outcome was change in VPT duration post intervention. Secondary outcomes included nephrotoxicity rates and carbapenem escalation. Results Prior to the intervention, 66 ML and 33 SCCA patients were started on the combination compared to 110 ML and 50 SCCA patients post-intervention. Overall, 50% of ML and 14% of SCCA patients were on surgical primary services. Amongst ML patients, there was a decrease in patients on VPT for > 4 days (22 % to 8%), incidence of renal injury (30.3% to 10%), and percentage of ID consults (53.0% to 43.6%). Escalation to a carbapenem was stable (4.5% to 4.5%). In SCCA patients the percentage of patients on VPT for > 4 days decreased slightly (18.2% to 15.2%), incidence of renal injury was stable (18.2% to 18%), percentage of ID consults increased (45.5% to 50.0%), and escalation to a carbapenem was stable (12.1% vs 13.5%). Conclusion Prospective audit and feedback of VPT was associated with a decrease in duration and nephrotoxicity in ML but not SCCA patients. The difference in outcomes could be due to the patient populations, primary services, or intervention process. This study highlights the importance of tailoring interventions even within the same medical system. Disclosures All Authors: No reported disclosures

104. Improving Efficiency of Antimicrobial Stewardship Reviews Using Artificial Intelligence Modelling

Background Antimicrobial stewardship programs (ASP) in hospitals improve antibiotic prescribing, slow antimicrobial resistance, reduce hospitalisation duration, mortality and readmission rates, and save costs. However, the strategy of prospective audit and feedback is laborious. In Singapore General Hospital (SGH), 10 reviews are required to identify 2 inappropriate cases. Limited manpower constraints ASP audits to only about 30% of antibiotics prescribed. This proof-of-concept study explored the feasibility of developing a predictive model to prioritise inappropriate antibiotic prescriptions for ASP review. Methods ASP-audited adult pneumonia patients from January 2016 to December 2018 in SGH were included. Patient data e.g., demographics, allergies, past medical history, and relevant laboratory investigations at each antibiotic use episode were extracted from electronic medical records and re-assembled through linking for analysis. Ground truth for model training was based on ASP-defined appropriateness for each encounter. The dataset was split into 80% and 20% for training and testing respectively. Three modelling techniques, XGBoost, decision tree and logistic regression, were assessed for their relative performance in terms of precision, sensitivity and specificity. Results There were 12471 unique patient encounters. Training was done on 10459 encounters and 39 data elements were included. When tested on 2012 encounters, the logistic regression model performed the best (86.7% sensitivity, 71.4% specificity). The model correctly classified 1377 out of 1388 (99.2%) encounters as “appropriate” (do not require ASP intervention). 624 antibiotic use encounters were classified as “inappropriate”, of which only 72 were truly inappropriate (positive predictive value for ASP intervention, PPV 11.5%). The low PPV was likely due to inadequate representation of “inappropriate” cases in the training dataset (4.1%). Applying this model would prioritise the number of immediate ASP reviews needed to identify cases for intervention by two-thirds, from 2012 to 624 (Figure 1). Figure 1. Illustration of AI benefits in ASP Conclusion ASPs can leverage on machine learning capabilities to improve audit efficiency. This can increase ASP’s productivity and staff’s job satisfaction as they are freed up to perform other work. Disclosures All Authors: No reported disclosures

78. Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Screen on Vancomycin Utilization for Respiratory Tract Infections

Background S. aureus, including MRSA, is a common colonizer of the nares. Recent data have shown that a negative MRSA nares screen by PCR has a negative predictive value of 98%. This implies that the absence of colonization can significantly reduce empiric vancomycin utilization. This study aimed to determine the utilization of MRSA nares screening on patients receiving vancomycin for respiratory tract infections (RTI) following the addition of the screen to the institutional RTI management guidelines. Methods This was a retrospective chart review of adult inpatients presenting to two community-teaching hospitals who were prescribed vancomycin for the treatment of RTIs. Patients were divided into pre-guideline (Jan-Feb 2019), post-guideline 1 (Jan-Feb 2020), and post-guideline 2 (Jan-Feb 2021) groups. The primary endpoint was the difference in percent of vancomycin orders discontinued within 24 hours of a negative screen. Secondary endpoints included the percent of screens ordered, re-initiation of vancomycin within seven days for RTI, and total vancomycin days of therapy (DOT) per 1000 patient days (PD). Results Of 493 vancomycin orders screened, 100 orders in each arm were analyzed. There was an absolute increase of 20.6% in vancomycin orders discontinued within 24 hours of a negative screen between the pre-guideline and post-guideline 2 groups (59.1% vs. 79.7%, p = 0.0177). When compared to the pre-guideline group, utilization of the screen increased by 15% in the post-guideline 1 group (48% vs. 63%, p = 0.0328) and 26% in the post-guideline 2 group (48% vs. 74%, p = 0.000164). There was no difference in re-initiation of vancomycin. A statistically significant reduction in total vancomycin DOT/1000PD from the pre-guideline to the post-guideline 1 and 2 groups (66 to 63 to 60, respectively) was also observed. Conclusion The addition of the MRSA nares screen to the institutional RTI guidelines increased utilization of the test and demonstrated a reduction in vancomycin utilization. With an increase in education, prospective audit and feedback, and prescriber comfort with the use of the MRSA nares screen in the post-guideline 2 group, there was significant improvement in MRSA nares screen utilization, vancomycin discontinuation after a negative screen, and vancomycin utilization. Disclosures All Authors: No reported disclosures