54. The Effect of Targeting High-Risk Patients for Antimicrobial Stewardship Intervention on Hospital-Onset Clostridioides Difficile Infection Rates

Abstract Background Clostridioides difficile infection contributes to significant burden on patients and the healthcare system, costing billions in excess costs every year for hospital care. Continued use of antibiotics after C. difficile infection diagnosis is a risk factor for recurrent infection. Also, individuals who have had a recurrence of C. difficile infection are at a higher risk of subsequent episodes. Methods This prospective, observational, pre-post study evaluated the effect of implementing a targeted antimicrobial stewardship initiative towards a high-risk target population on the rate of in-hospital C. difficile infection rates. High-risk targets were identified through an electronic health system report of admitted patients at a large academic medical center who were toxin assay positive or had a documented history of C. difficile infection. Subjects who met the criteria were assessed for interventions by the pharmacy-driven antimicrobial stewardship service. The primary outcome compared the hospital-onset C. difficile rates and standardized infection ratio (SIR) before and after implementation of the initiative. The SIR is reported to the National Healthcare Safety Network (NHSN) and is calculated as a ratio between the number of observed and predicted infections, which is adjusted for facility-specific factors that contribute C. difficile risk. Negative binomial regression was used to calculate the predicted C. difficile infections in the SIR. Poisson regression was used to generate a 95% prediction interval for the predicted C. difficile infection rate. Results The mean age of subjects was 63 years old and 85% had no history of prior C. difficile infection. The most common intervention was de-escalation of antibiotics (46%). The post-implementation SIR was 0.55 and hospital-onset C. difficile rate was 13, both of which were significantly lower than predicted. Conclusion Targeting patients who have a history of or are newly diagnosed with C. difficile infection may decrease hospital-onset C. difficile rates. Disclosures All Authors: No reported disclosures


Optimizing Transitions of Care Antimicrobial Prescribing at a Community Teaching Hospital
Kushal Naik, PharmD 1 ; Jeremy J. Frens, PharmD 1 ; Jordan R. Smith, PharmD 2 ; 1 Cone Health, Greensboro, North Carolina; 2 High Point University, High Point, NC Session: P-04. Antimicrobial Stewardship: Outcomes Assessment (clinical and economic) Background. Antimicrobial stewardship integral to patient care. Institutions with stewardship decrease antibiotic use, cost, and antibiotic-associated infections. However, few efforts have been formally made to address discharge antimicrobial prescribing, even though many patients started on antibiotic therapy in the hospital are prescribed oral antibiotics to complete their regimens.
Methods. This was an IRB approved, quasi-experimental, pre-post study. Patients were included if they were >18 years and were discharged from the hospital with an oral antibiotic prescription. Patients discharged against medical advice, prescribed indefinite prophylactic antimicrobial therapy for legitimate reasons, or discharged to a skilled nursing facility were excluded. The retrospective group evaluated a random sample of patients discharged in 2/2020. The prospective group included patients discharged between 1/2021 -6/2021. In the prospective group, a clinical pharmacist assessed the indication for antibiotics and pended discharge antibiotic prescriptions for physician review. Antibiotic choice and duration of therapy were based on local and national guidelines.

Patient Screening for Inclusion and Exclusion
Breakdown of patients screened, included, and excluded for study Results. 86 (53.1%) of 162 retrospective patients from 2/2020 prior to implementation of the program demonstrated were discharged on inappropriate antimicrobial therapy with excessive duration being the principal driver for inappropriateness. In the prospective group of 64 patients, the rate of patients discharged on inappropriate antibiotics decreased to 28.1% (p=0.001). The duration of inappropriate therapy decreased from a mean of 4.6 days to 2.7 days (p=0.001). 45 (70.3%) of 64 prospective pharmacist's interventions were accepted by providers.
Study Outcomes Outcomes including overall appropriate prescribing, appropriate duration, spectrum, frequency, and dose, as well as days of inappropriate therapy Conclusion. Literature demonstrates that prospective evaluation of discharge antibiotics by a clinical pharmacist is effective in improving appropriateness of discharge antibiotic prescriptions, optimizing duration of outpatient antibiotics as well as reducing unnecessarily broad-spectrum therapy. The prospective results from this study demonstrate that this innovative approach can improve outpatient oral antibiotic prescribing and provide a framework for other institutions to implement similar programs.
Disclosures. Background. Clostridioides difficile infection contributes to significant burden on patients and the healthcare system, costing billions in excess costs every year for hospital care. Continued use of antibiotics after C. difficile infection diagnosis is a risk factor for recurrent infection. Also, individuals who have had a recurrence of C. difficile infection are at a higher risk of subsequent episodes.
Methods. This prospective, observational, pre-post study evaluated the effect of implementing a targeted antimicrobial stewardship initiative towards a high-risk target population on the rate of in-hospital C. difficile infection rates. High-risk targets were identified through an electronic health system report of admitted patients at a large academic medical center who were toxin assay positive or had a documented history of C. difficile infection. Subjects who met the criteria were assessed for interventions by the pharmacy-driven antimicrobial stewardship service. The primary outcome compared the hospital-onset C. difficile rates and standardized infection ratio (SIR) before and after implementation of the initiative. The SIR is reported to the National Healthcare Safety Network (NHSN) and is calculated as a ratio between the number of observed and predicted infections, which is adjusted for facility-specific factors that contribute C. difficile risk. Negative binomial regression was used to calculate the predicted C. difficile infections in the SIR. Poisson regression was used to generate a 95% prediction interval for the predicted C. difficile infection rate.
Results. The mean age of subjects was 63 years old and 85% had no history of prior C. difficile infection. The most common intervention was de-escalation of antibiotics (46%). The post-implementation SIR was 0.55 and hospital-onset C. difficile rate was 13, both of which were significantly lower than predicted.
Conclusion. Targeting patients who have a history of or are newly diagnosed with C. difficile infection may decrease hospital-onset C. difficile rates.
Disclosures. All Authors: No reported disclosures No ESBL comment is reported at UWML. We aimed to determine whether the methodology in identification and reporting of ESBL-E from blood cultures between two hospitals has an impact on time to preferred therapy with a carbapenem antibiotic.

Impact of Testing Methodology and Reporting on Time to Preferred Antibiotic Therapy in Extended Spectrum Beta-Lactamase producing Enterobacteriaceae (ESBL-E) Bloodstream Infections
Methods. Retrospective observational study conducted at UWML and HMC in Seattle, WA between 1/10/2015 and 9/15/2020. Adult patients were eligible if they had ≥1 positive blood culture with an Enterobacteriaceae isolate resistant to ceftriaxone and were on antibiotic treatment. The primary outcome was the difference in time to preferred definitive therapy with a carbapenem antibiotic in patients an ESBL-E bloodstream infection (BSI)  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;). 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.
Disclosures. All Authors: No reported disclosures