Days Of Antibiotic Therapy Research Articles

927. Successful Implementation of an Inpatient Fluoroquinolone (FQ) Pre-Authorization (PA) Program at a Tertiary Care Academic Center and Associated Changes in Antibiotic Use, Antibiogram Susceptibility, and Provider Behavioral Changes

Abstract Background In 2017, our adult tertiary care academic hospital in the Midwest implemented an inpatient fluoroquinolone (FQ) prior authorization (PA) policy using the electronic health record (EHR) as a stewardship tool. We examined the changes in antibiotic use, the antibiogram, and antibiotic use at an affiliated hospital without PA but staffed by physicians from the PA site. Methods This quasi-experimental study used a pre-post implementation design to evaluate a PA policy at our University Hospital requiring approval of all inpatient FQ use from the antimicrobial stewardship physician or infectious disease consult teams. Time periods consisted of 2.5 year pre-implementation, 9-month wash-in (pilot on 2 wards), and 5-year post-implementation periods. Monthly antibiotic use in days of therapy per 1000 patient days (DOT/KPD) and antibiogram data, limited to first inpatient culture per patient per week from any anatomic site, were collected. Monthly FQ use from an affiliated hospital without the restriction policy staffed by physicians from the University Hospital was also collected. Changes in antibiotic use were examined using t-test, or Mann-Whitney Rank Sum, and antibiotic susceptibility rates were compared using z-test. Results Following implementation of PA, FQ use decreased by 76% (-53.2 DOT/KPD, p< 0.001) (Fig. 1). FQ use also declined from 26.4 DOT/KPD to 7.7 DOT/KPD (p< 0.001) at the affiliated hospital without PA but staffed by physicians from University Hospital. Changes in gram-negative agents use are shown in Table 1, with greatest increase noted for ceftriaxone (∼50%). The ciprofloxacin inpatient antibiogram improved significantly (Table 2); whereas, a slight decline in susceptibility was noted for ceftriaxone and cefepime. Figure 1.Fluoroquinolone use across study periods. Wash-in period included a pilot fluoroquinolone prior authorization in 2 wards. Abbreviations: Days of Therapy (DOT); patient days (PD) Table 1.Mean antibiotic days of therapy during each study period. Successive shortages for cefepime and piperacillin-tazobactam during the wash-in period, as indicated by NA. Table 2.Proportion of susceptible isolates pre- and post-implementation of Fluoroquinolone prior-authorization.Pip-tazo, piperacillin-tazobactam; %S, the percent susceptible for Pre- or Post-implementation periods; * indicates significant improvement and ¥ significant decline (p<0.05) pre vs post; R indicates intrinsic resistance. Conclusion FQ PA leads to significant and sustained decline in FQ use, indicating that suitable alternative choices exist for most hospitalized patients. Decreased FQ use was associated with increased use of cephalosporins, mainly ceftriaxone. As might be expected, changes in use were associated with subsequent changes in the antibiogram. This intervention was associated with a significant decline in FQ use at a site without the restriction policy and the EHR modifications, suggesting successful diffusion of educational and behavioral changes. Disclosures Lindsay Taylor, MD, Merck: Grant/Research Support Jessica S. Tischendorf, MD, MS, Merck: Grant/Research Support.

1656. Impact of Pharmacist Intervention on Antibiotic Prescribing at Hospital Discharge for Community-Acquired Pneumonia, Urinary Tract Infection, and Skin and Soft Tissue Infections

Abstract Background The high incidence of suboptimal antibiotic use at transitions of care represents a novel area for antimicrobial stewardship for community-acquired pneumonia (CAP), urinary tract infection (UTI), and skin and soft tissue infections (SSTIs). The objective of this study was to investigate the role of a pharmacist intervention at discharge to improve antibiotic use. Methods This was a single-center, retrospective, crossover analysis of patients admitted to general medicine units from 11/1/21 to 3/31/22 with a diagnosis of CAP, UTI, or SSTI. The study was divided into two phases separated by a one-month washout. Each two-month phase included two pre-specified units, an intervention and control. During phase 2, the intervention and control units were switched. Patients on antibiotics identified for discharge were reviewed and interventions were communicated by the pharmacist to the provider. Interventions were made based on predefined guidance for oral step-down therapy and total duration. The primary outcome, discharge antibiotic days of therapy (DOT), was compared between the intervention and control cohorts. Secondary outcomes included total DOT, hospital length of stay (LOS), 30-day readmission, and appropriateness of drug selection, dose, and duration. Results Records of 161 patients were included in this study, 85 in the intervention cohort (47 in phase 1, 38 in phase 2) and 76 in the control (41 in phase 1, 35 in phase 2). Overall discharge DOT was 3 (IQR 0–4.5) in the intervention cohort and 3 (IQR 0-5) in the control cohort (P = 0.8), and overall total DOT was 7 (IQR 5-9) and 7 (IQR 5-10) respectively (P = 0.27). Patients in the intervention group were more likely to have appropriate total duration (61.2% vs 44.7%, P = 0.001) and discharge duration of antibiotics (67.1% vs 53.9%, P = 0.013) for all three indications based on predefined guidance. Hospital LOS was 4 (IQR 3-5) vs 5 days (IQR 3-6.3) in the intervention and control cohorts (P = 0.001) respectively, and a lower 30-day readmission (14.1% vs. 23.7%, resp.). Conclusion Despite similar antibiotic DOTs, pharmacist intervention at discharge appeared to improve overall antibiotic total duration and discharge duration for CAP, UTI, and SSTI. Opportunities to improve discharge stewardship processes should be further explored. Disclosures Joseph L. Kuti, PharmD, Abbvie: Honoraria|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Contrafect: Grant/Research Support|Entasis: Grant/Research Support|Merck and Co: Grant/Research Support|Roche Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Summit: Grant/Research Support David P. Nicolau, PharmD, Shionogi: Grant/Research Support.

276. Factors Predicting Bacterial Coinfection in Hospitalized COVID-19 Patients

Abstract Background Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes. Methods A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection. Results A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03). Conclusion As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.

Beta-lactam allergies, surgical site infections, and prophylaxis in solid organ transplant recipients at a single center: A retrospective cohort study.

Beta-lactam allergies (BLAs) are common in hospitalized patients, including transplant recipients. BLA is associated with decreased use of preferred surgical site infection (SSI) prophylaxis and increased SSIs, but this has not been studied in the transplant population. We reviewed adult heart, kidney, and liver transplant recipients between January 1, 2016 and December 31, 2019 to characterize reported BLA and collect SSI prophylaxis regimens at time of transplant. We compared the use of preferred SSI prophylaxis and SSI incidence based on reported BLA status. Post hoc we collected antibiotic days of therapy (DOT) (excluding pneumocystis prophylaxis) in the 30-day period posttransplant for patients without SSI. We utilized descriptive statistics for comparisons. Of 691 patients included (116 heart, 400 kidney, and 175 liver transplant recipients), 118 (17%) reported BLA. Rash and hives were the two most reported BLA reactions (36% and 24%), categorized as potential T-cell mediated and IgE mediated, respectively. Preferred SSI prophylaxis was prescribed in 13 (11%) patients with BLA and 573 (92%) without BLA (p < .001). No difference could be detected in SSI incidence between BLA and non-BLA patients (4.2vs. 4.3%, p = 1.0). Of 659 without SSI, 169 (25.6%) received antibiotics within 30 days of transplant; mean antibiotic DOT for BLA and non-BLA patients were 3.5 ± 8.0versus 2.3 ± 5.8, p = .12. BLA transplant recipients received nonpreferred SSI prophylaxis more frequently than non-BLA recipients, but there was no difference in 30-day SSIs between the groups. One-fourth of solid organ transplant recipients received systemic antibiotics within 30 days of transplant.

Impact of a Medication Reconciliation Pharmacist Program on Appropriateness of Community-Acquired Pneumonia Treatment Durations at Hospital Discharge.

Antimicrobial stewardship programs have made large efforts to minimize the inappropriate use of antibiotics. Implementation of these programs can be challenging, since many institutions have limited resources. Utilizing resources that already exist may be beneficial, including medication reconciliation pharmacist (MRP) programs. This study aims to evaluate the impact of a MRP program on appropriateness of community-acquired pneumonia (CAP) treatment durations at hospital discharge. This study was a retrospective, observational, single-center study comparing the total days of antibiotic therapy for CAP in the preintervention period (9/2020-11/2020) versus the post-intervention period (9/2021-11/2021). Implementation of a new clinical intervention occurred between the 2 periods and included education to MRPs on appropriate CAP treatment durations and on documentation of recommendations. Data was collected utilizing a chart review of the electronic medical record of patients diagnosed with CAP using ICD-10 codes. The primary objective of this study was to compare the total days of antibiotic therapy in the pre-intervention period versus the postintervention period. One-hundred fifty-five patients were included in the primary analysis. When observing total days of antibiotic therapy, there was no change from the pre-intervention period at 8 days compared to the postintervention period (P = .109). When analyzing antibiotic days of therapy at discharge, there was a decrease from 4.55 days in the preintervention period compared to 3.8 days in the post-intervention period (P = .109). The incidence of those with appropriate treatment durations, defined as 5 to 7 days of antibiotic therapy, was higher in the post-intervention period (26.5% in the pre-intervention group vs 37.9% in the post-intervention group, P = .460). There was a non-statistically significant decrease in median days of antimicrobial therapy for CAP at hospital discharge after implementation of a new clinical intervention targeting antibiotic days of therapy. Though median total antibiotic days of therapy were similar between both time periods, patients had an overall increase in incidence of appropriate duration of therapy, defined as 5 to 7 days, after intervention. Further studies are necessary to show how MRPs have a positive impact on improving outpatient antibiotic prescribing at hospital discharge.

Novel expansion of a well-established antimicrobial stewardship program: Enhancing program efficiency and reach.

To evaluate efficiency and impact of a novel antimicrobial stewardship program (ASP) prospective-audit-with-feedback (PAF) review process using the Cerner Multi-Patient Task List (MPTL). Retrospective cohort study. A 367-bed free-standing, pediatric academic medical center. The ASP PAF review process expanded to monitor all systemic and inhaled antibiotics through use of the MPTL on July 23, 2020. Average number of daily ASP reviews, absolute number of monthly interventions, and time to conduct ASP reviews were compared between the preimplementation period and the postimplementation period following expansion. Antibiotic days of therapy (DOT) per 1,000 patient days for overall and select antibiotics were compared between periods. ASP intervention characteristics were assessed. Average daily ASP reviews significantly increased following program expansion (9 vs 14 reviews; P < .0001), and the absolute number of ASP interventions each month also increased (34 vs 52 interventions; P ≤ .0001). Time to conduct daily ASP reviews increased in the postimplementation period (1.03 vs 1.32 hours). Overall antibiotic DOT per 1,000 patient days significantly decreased in the postimplementation period (457.9 vs 427.9; P < .0001) as well as utilization of select, narrow-spectrum antibiotics such as ampicillin and clindamycin. Intervention type and antibiotics were similar between periods. The ASP documented 128 "nonantibiotic interventions" in the postimplementation period, including culture and/or susceptibility testing (32.8%), immunizations (25.8%), and additional diagnostic testing (22.7%). Implementation of an ASP PAF review process using the MPTL allowed for efficient expansion of a pre-existing ASP and a decrease in overall antibiotic utilization. ASP documentation was enhanced to fully track the impact of the program.

Analysis of an Antibiotic Stewardship Program for Asymptomatic Bacteriuria in the Veterans Affairs Health Care System

Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited. To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB. This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect urine cultures and who order, dispense, or administer antibiotics. Clinical outcomes were measured in all patients in a study unit during the study period. Data were analyzed from July 6, 2020, to May 24, 2021. Case-based teaching on how to apply an evidence-based algorithm to distinguish urinary tract infection and ASB. The intervention was implemented through external facilitation by a centralized coordinating center, with a site champion at each intervention site serving as an internal facilitator. Urine culture orders and days of antibiotic therapy (DOT) and length of antibiotic therapy in days (LOT) associated with urine cultures, standardized by 1000 bed-days, were obtained from the VA's Corporate Data Warehouse. Of 11 299 patients included, 10 703 (94.7%) were men, with a mean (SD) age of 72.6 (11.8) years. The decrease in urine cultures before and after the intervention was not significant in intervention sites per segmented regression analysis (-0.04 [95% CI, -0.17 to 0.09]; P = .56). However, difference-in-differences analysis comparing intervention with comparison sites found a significant reduction in the number of urine cultures ordered by 3.24 urine cultures per 1000 bed-days (P = .003). In the segmented regression analyses, the relative percentage decrease of DOT in the postintervention period at the intervention sites was 21.7% (P = .007), from 46.1 (95% CI, 28.8-63.4) to 37.0 (95% CI, 22.6-51.4) per 1000 bed-days. The relative percentage decrease of LOT in the postintervention period at the intervention sites was 21.0% (P = .001), from 36.7 (95% CI, 23.2-50.2) to 29.6 (95% CI, 18.2-41.0) per 1000 bed-days. The findings of this quality improvement study suggest that an individualized intervention for antibiotic stewardship for ASB was associated with a decrease in urine cultures and antibiotic use when implemented at multiple sites via external and internal facilitation. The electronic health record database-derived outcome measures and centralized facilitation approach are both suitable for dissemination.

P02 Assessment of the appropriateness of antibiotic prescribing in an acute UK hospital using a national audit tool: a single-centre retrospective cohort study

BackgroundDefining the gold standard for appropriate antibiotic prescribing is challenging due to the subjective nature of evaluating quality in prescribing. In 2017 the UK Government Scientific Advisory Committee on Antimicrobial Prescribing, Resistance and Healthcare Associated Infection (APRHAI) used the Delphi process to define appropriate antibiotic prescribing, and developed an audit tool that supports patient-level assessment of antibiotic appropriateness in NHS hospitals.ObjectivesTo quantify excess antibiotic use in a 750-bed acute hospital in the south-west of England (bottom 20th centile on PHE Fingertips for total antibiotic prescribing), and to determine where in the prescribing process the opportunity to safely reduce antibiotic use is: (A) initiation, (B) the pre-72 h review, or (C) course length optimization.MethodsThe EPMA system was used to identify patients discharged from medical specialties in August 2020 who had received at least one dose of antibiotic. Patients were grouped by discharging medical specialty, as follows: acute medicine, elder care, renal, endocrine, gastroenterology, respiratory and cardiology. Medical notes for 25% of discharges from each specialty were requested and audited against the APRHAI audit tool. A junior doctor completed the audit form for each patient with the case then discussed by two infection specialists until consensus was reached. Excess days of antibiotic therapy (DOTs) were calculated for each of the three timepoints (A–C).ResultsIn total, 184 of 647 (28%) patients discharged from medical specialties were audited: 85 female, 99 male, median age 69 years (IQR 60–82), total DOTs 1658 of which 403 (24%) were excess. Excess DOTs by timepoint: A (initiation) 112 (28%), B (pre-72 h review) 184 (46%), C (course length) 107 (27%). Ninety-four of 187 (50%) of patients recorded zero excess DOTs.ConclusionsWe did not identify any excess DOTs in half of all patients initiated on antibiotics. However, in the other half we identified a significant proportion of excess DOTs with most excess DOTs at the pre-72 h review.

Clinical Characteristics Associated with Bacterial Bloodstream Coinfection in COVID-19.

IntroductionInappropriate antibiotic use in COVID-19 is often due to treatment of presumed bacterial coinfection. Predictive factors to distinguish COVID-19 from COVID-19 with bacterial coinfection or bloodstream infection are limited.MethodsWe conducted a retrospective cohort study of 595 COVID-19 patients admitted between March 8, 2020, and April 4, 2020, to describe factors associated with a bacterial bloodstream coinfection (BSI). The primary outcome was any characteristic associated with BSI in COVID-19, with secondary outcomes including 30-day mortality and days of antibiotic therapy (DOT) by antibiotic consumption (DOT/1000 patient-days). Variables of interest were compared between true BSI (n = 25) and all other COVID-19 cases (n = 570). A secondary comparison was performed between positive blood cultures with true BSI (n = 25) and contaminants (n = 33) on antibiotic use.ResultsFever (> 38 °C) (as a COVID-19 symptom) was not different between true BSI (n = 25) and all other COVID-19 patients (n = 570) (p = 0.93), although it was different as a reason for emergency department (ED) admission (p = 0.01). Neurological symptoms (ED reason or COVID-19 symptom) were significantly higher in the true BSI group (p < 0.01, p < 0.01) and were independently associated with true BSI (ED reason: OR = 3.27, p < 0.01; COVID-19 symptom: OR = 2.69, p = 0.03) on multivariate logistic regression. High (15–19.9 × 109/L) white blood cell (WBC) count at admission was also higher in the true BSI group (p < 0.01) and was independently associated with true BSI (OR = 2.56, p = 0.06) though was not statistically significant. Thirty-day mortality was higher among true BSI (p < 0.01). Antibiotic consumption (DOT/1000 patient-days) between true BSI and contaminants was not different (p = 0.34). True bloodstream coinfection was 4.2% (25/595) over the 28-day period.ConclusionTrue BSI in COVID-19 was associated with neurological symptoms and nonsignificant higher WBC, and led to overall higher 30-day mortality and worse patient outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00636-6.

Implementation of an Antibiotic Stewardship Program in Long-term Care Facilities Across the US

Antibiotic overuse in long-term care (LTC) is common, prompting calls for antibiotic stewardship programs (ASPs) designed for specific use in these settings. The optimal approach to establish robust, sustainable ASPs in LTC facilities is unknown. To determine if the Agency for Healthcare Research and Quality (AHRQ) Safety Program for Improving Antibiotic Use, an educational initiative to establish ASPs focusing on patient safety, is associated with reductions in antibiotic use in LTC settings. This quality improvement study including 439 LTC facilities in the US assessed antibiotic therapy data following a pragmatic quality-improvement program, which was implemented to assist facilities in establishing ASPs and with antibiotic decision-making. Training was conducted between December 2018 and November 2019. Data were analyzed from January 2019 to December 2019. Fifteen webinars occurred over 12 months (December 2018 to November 2019), accompanied by additional tools, activities, posters, and pocket cards. All clinical staff were encouraged to participate. The primary outcome was antibiotic starts per 1000 resident-days. Secondary outcomes included days of antibiotic therapy (DOT) per 1000 resident-days, the number of urine cultures per 1000 resident-days, and Clostridioides difficile laboratory-identified events per 10 000 resident-days. All outcomes compared data from the baseline (January-February 2019) to the completion of the program (November-December 2019). Generalized linear mixed models with random intercepts at the site level assessed changes over time. Of a total 523 eligible LTC facilities, 439 (83.9%) completed the safety program. The mean difference for antibiotic starts from baseline to study completion per 1000 resident-days was -0.41 (95% CI, -0.76 to -0.07; P = .02), with fluoroquinolones showing the greatest decrease at -0.21 starts per 1000 resident-days (95% CI, -0.35 to -0.08; P = .002). The mean difference for antibiotic DOT per 1000 resident-days was not significant (-3.05; 95% CI, -6.34 to 0.23; P = .07). Reductions in antibiotic starts and use were greater in facilities with greater program engagement (as measured by webinar attendance). While antibiotic starts and DOT in these facilities decreased by 1.12 per 1000 resident-days (95% CI, -1.75 to -0.49; P < .001) and 9.97 per 1000 resident-days (95% CI, -15.4 to -4.6; P < .001), respectively, no significant reductions occurred in low engagement facilities. Urine cultures per 1000 resident-days decreased by 0.38 (95% CI, -0.61 to -0.15; P = .001). There was no significant change in facility-onset C difficile laboratory-identified events. Participation in the AHRQ safety program was associated with the development of ASPs that actively engaged clinical staff in the decision-making processes around antibiotic prescriptions in participating LTC facilities. The reduction in antibiotic DOT and starts, which was more pronounced in more engaged facilities, indicates that implementation of this multifaceted program may support successful ASPs in LTC settings.

The impact of the COVID-19 pandemic on antimicrobial prescribing at a specialist paediatric hospital: an observational study.

BackgroundThe COVID-19 pandemic has severely impacted healthcare delivery and there are growing concerns that the pandemic will accelerate antimicrobial resistance.ObjectivesTo evaluate the impact of the COVID-19 pandemic on antibiotic prescribing in a tertiary paediatric hospital in London, UK.MethodsData on patient characteristics and antimicrobial administration for inpatients treated between 29 April 2019 and Sunday 28 March 2021 were extracted from the electronic health record (EHR). Interrupted time series analysis was used to evaluate antibiotic days of therapy (DOT) and the proportion of prescribed antibiotics from the WHO ‘Access’ class.ResultsA total of 23 292 inpatient admissions were included. Prior to the pandemic there were an average 262 admissions per week compared with 212 during the pandemic period. Patient demographics were similar in the two periods but there was a shift in the specialities that patients had been admitted to. During the pandemic, there was a crude increase in antibiotic DOTs, from 801 weekly DOT before the pandemic to 846. The proportion of Access antibiotics decreased from 44% to 42%. However, after controlling for changes in patient characteristics, there was no evidence for the pandemic having an impact on antibiotic prescribing.ConclusionsThe patient population in a specialist children’s hospital was affected by the COVID-19 pandemic, but after adjusting for these changes there was no evidence that antibiotic prescribing was significantly affected by the pandemic. This highlights both the value of routine, high-quality EHR data and importance of appropriate statistical methods that can adjust for underlying changes to populations when evaluating impacts of the pandemic on healthcare.

Hidden No More: Capturing the Full Picture of Prolonged Perioperative Antibiotic Prophylaxis.

Hidden No More: Capturing the Full Picture of Prolonged Perioperative Antibiotic Prophylaxis.

170. Antimicrobial Use Before and During COVID-19 – Data from 108 VA Facilities

BackgroundIncreased antibiotic prescribing rates during the early phases of the COVID-19 pandemic have been widely reported. We previously reported that while both antibiotic days of therapy (DOT) and total days present (DP) declined in the first 5 months of 2020 at Veterans Affairs (VA) acute care facilities nationwide relative to the comparable period in 2019, antibiotic DOT per 1000 DP increased by 11.3%, largely reversing declines in VA antimicrobial utilization from 2015 – 2019. We now evaluate whether these changes in antibiotic use persisted throughout the COVID-19 pandemic.MethodsData on antibacterial use, patient days present, and COVID-19 care for acute inpatient care units in 108 VA level 1 and 2 facilities were extracted through the VA Informatics and Computing Infrastructure; level 3 facilities which provide limited acute inpatient services were excluded. DOT per 1000 DP were calculated and stratified by CDC-defined antibiotic classes.ResultsFrom 1/2020 to 2/2021, care for 34,096 COVID-19 patients accounted for 13% of all acute inpatient days of care in the VA. Following the onset of COVID-19 pandemic, monthly total acute care antibiotic use increased from 533 DOT/1000 DP in 1/2020 to a peak of 583 DOT/1000 DP in 4/2020; during that month COVID-19 patients accounted for 13% of all DP (Figure). In subsequent months, total antibiotic use declined such that for the full year the change of antibiotic use from 2019 to 2020 (a decrease of 18 DOT/1000 DP) was similar to the rate of decline from 2015 to 2019 (mean decrease of 13 DOT/1000 DP; Table). The decreased DOT/1000 DP from 5/2020 to 2/2021 occurred even as the percentage of all DP due to COVID-19 peaked at 14 - 24% from 11/2020 to 2/2021. ConclusionAlthough rates of antibiotic use increased within the VA during the early phases of the COVID-19 pandemic, rates subsequently decreased to below previous baseline levels even as the proportion of COVID-19 DP spiked between 11/2020 and 02/2021. Although the degree to which the initial increase in antibiotic use is attributable to concerns of bacterial superinfection versus changes in case-mix (e.g., decreased elective admission) remains to be assessed, these data support the continued effectiveness of antimicrobial stewardship programs in the VA. Disclosures Matthew B. Goetz, MD, Nothing to disclose

327. Assessment of Bacterial Co-infection Rates and Antibiotic Exposure in COVID-19 Patients

BackgroundCOVID-19 pandemic data suggest risk for bacterial co-infection upon hospital presentation remain extremely low. Despite low co-infection rates, antibiotics are prescribed for most patients. Current data are limited regarding institutional-specific change in antibiotic use over the course of the pandemic. Given the low rates of co-infections, Saint Luke’s Health System’s COVID-19 Treatment Taskforce developed a COVID-19 evaluation and treatment order set which included procalcitonin (PCT) . As co-infection literature emerged, active education was provided, and order sets were modified to provide passive education regarding co-infection rates. We aimed to assess antibiotic practice changes as data and strategies to influence use evolved during the pandemic.MethodsThis was a multi-center, single health-system retrospective cohort study. Ten community hospitals and 1 academic medical center were included in analysis. Inclusion criteria were age ≥18 years, admitted during April or September 2020 and had a positive COVID-19 result on admission. Patients were excluded if they were readmitted for COVID-19 related issues. Both primary and secondary outcomes were analyzed from the first 7 days after admission. The primary outcome was rate of respiratory bacterial co-infections. This was determined through sputum and blood cultures, urinary antigens including Streptococcus pneumoniae and Legionella, and PCT. Secondary outcomes included rate of antibiotic use, antibiotic days of therapy (DOT), length of therapy, and antibiotic use trends.Baseline Characteristics ResultsA total of 294 patients were included with 69 patients in April 2020 and 225 in September 2020. Primary and secondary results are shown in Table 2. Rate of culture-confirmed bacterial co-infection when examining April 2020 was 4.38% and 4.44 % in September 2020. Antibiotic uses, antibiotic DOT, and length of therapy were all significantly lower in September 2020 compared to April 2020. ConclusionOur results show bacterial co-infections were extremely low in our health system. Despite positive trends in antibiotic use, prescribing remained high. More targeted interventions to decrease antibiotic exposure in COVID-19 patients are needed. Disclosures All Authors: No reported disclosures

14. Effects of an Opt-Out Protocol for Antibiotic De-escalation among Selected Patients with Suspected Sepsis: The DETOURS Trial

BackgroundSepsis guidelines recommend daily review to de-escalate or stop antibiotics in appropriate patients. We conducted a randomized controlled trial (NCT03517007) of an opt-out protocol to decrease unnecessary antibiotics in selected patients with suspected sepsis.MethodsWe evaluated non-ICU adults remaining on broad-spectrum antibiotics with negative blood cultures at 48-96 hours at ten U.S. hospitals during September 2018-May 2020. A 23-item safety check excluded patients with ongoing signs of infection, concerning or inadequate microbiologic data, or high-risk conditions (Figure 1). Eligible patients were randomized to the opt-out protocol vs. usual care. The primary outcome was 30-day post-enrollment antibacterial days of therapy (DOT). Clinicians caring for intervention patients were contacted by a pharmacist or physician to encourage antibiotic discontinuation or de-escalation using opt-out language, discuss rationale for continuing antibiotics, working diagnosis, and de-escalation and duration plans. Hurdle models separately compared the odds of antibiotic continuation and DOT distributions among those who continued antibiotics.Components of the De-Escalating Empiric Therapy: Opting-OUt of Rx in Selected patients with Suspected Sepsis (DETOURS) Trial Protocol ResultsAmong 9606 screened, 767 (8%) were enrolled (Figure 2). Common reasons for exclusion were antibiotics given prior to blood culture (35%), positive culture from non-blood sites (26%), and increased oxygen requirement (21%). Intervention patients had 32% lower odds of antibiotic continuation (79% vs. 84%, OR 0.68, 95% confidence interval [0.47, 0.98]). DOT distributions among those who continued antibiotics were similar (ratio of means 1.06 [0.88-1.26], Figure 3). Fewer intervention patients were exposed to extended-spectrum agents (38% vs. 44%). Common reasons for continuing antibiotics were treatment of localized infection (76%) and belief that stopping antibiotics was not safe (31%). Safety outcomes such as mortality, readmission, sepsis relapse, C. difficile, and length of stay did not differ.DETOURS Trial Flow Diagram Flow of participants through the DETOURS Trial.Observed Days of Antibiotic Therapy Among Intervention and Control Subjects in the DETOURS Trial Post-enrollment days of antibiotic therapy among 767 DETOURS Trial participants in 10 US acute care hospitals within 30 days after enrollment. Dark pink color indicates percent overlap between intervention (purple) and control (light pink) groups.ConclusionIn this patient-level randomized trial of a stewardship intervention, the opt-out de-escalation protocol targeting selected patients with suspected sepsis resulted in more antibiotic discontinuations but did not affect safety events.Disclosures Rebekah W. Moehring, MD, MPH, UpToDate, Inc. (Other Financial or Material Support, Author Royalties) Michael Z. David, MD PhD, GSK (Board Member) Michael Klompas, MD, MPH, UpToDate (Other Financial or Material Support, Chapter Author)

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

BackgroundFollowing 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.MethodsThis 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).ResultsA 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). ConclusionDespite 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.)

Antibiotic spectrum index: A new tool comparing antibiotic use in three NICUs.

Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures. We extracted data from patients admitted to 3 level-4 NICUs for 2 years at 2 sites and for 1 year at a third site. We calculated the ASI per antibiotic days and DOT per patient days for all admitted VLBW infants <32 weeks gestational age. Clinical variables were compared as percentages or as days per 1,000 patient days. We used Kruskal-Wallis tests to compare continuous variables across the 3 sites. Demographics were similar for the 734 VLBW infants included. The site with the highest DOT per patient days had the lowest ASI per antibiotic days and the site with the highest mortality and infection rates had the highest ASI per antibiotic days. Antibiotic utilization varied by center, particularly for choice of broad-spectrum coverage, although the organisms causing infection were similar. An antibiotic spectrum index identified differences in prescribing practice patterns among 3 NICUs unique from those identified by standard antibiotic use metrics. Site differences in infection rates and unit practices or guidelines for prescribing antibiotics were reflected in the ASI. This comparison uncovered opportunities to improve antibiotic stewardship and demonstrates the utility of this metric for comparing antibiotic exposures among NICU populations.

Impact of Order-Set Modifications and Provider Education Following Guideline Updates on Broad-Spectrum Antibiotic Use in Patients Admitted With Community Acquired Pneumonia.

Purpose: Following updates to the Infectious Diseases Society of America (IDSA) practice guidelines for the Diagnosis and Treatment of Adults with Community-acquired Pneumonia in 2019, Hartford HealthCare implemented changes to the community acquired pneumonia (CAP) order-set in August 2020 to reflect criteria for the 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 a diagnosis of CAP from September 1, 2019 to October 31, 2019 (pre-intervention) and September 1, 2020 to October 31, 2020 (post-intervention). Patients were identified using ICD-10 codes (A48.1, J10.00-J18.9) indicating lower respiratory tract infection. 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 cohorts, respectively. There were no differences in order-set usage (10% vs 11.3%, P = .642) between the pre- and post-intervention cohort, 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 < .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 = .003). Hospital LOS was shorter 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: Implementation of an updated CAP order-set with accompanying provider education was associated with reduced use of broad-spectrum antibiotics. Opportunities to improve compliance and thus further increase guideline-concordant therapy require investigation.

Decreasing ICU-associated Clostridioides difficile infection through fluoroquinolone restriction, the FIRST trial: a study protocol

IntroductionClostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the USA, having high incidence in intensive care units (ICU). Antibiotic use increases risk of CDI, with...

Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer.

Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77–6.18), days of therapy (DOT) ≥ 2 weeks (HR = 2.56, 95% CI: 1.30–5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.