bluuebunny/crossref_metadata_2025_split huggingface dataset:
675. Sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections: A detailed safety review from the pivotal phase 3, global, randomized, active-controlled trial (ATTACK)
Authors: Lewis Drew , Rana Khurram , Poirier Gabrielle , Altarac David 
Published: December 2022

Abstract

Background
SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. The primary efficacy endpoint, 28-day all-cause mortality, was achieved. The safety profile of SUL-DUR versus colistin is presented here.

Methods
ATTACK consisted of two parts. Part A was the randomized, non-inferiority portion in ABC hospital-acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, ventilated pneumonia, or bacteremia; patients were randomized 1:1 to SUL-DUR or colistin for 7 to 14 days. Part B provided open label SUL-DUR for patients intolerant of colistin or with colistin-resistant ABC. Safety data presented here include both Part A and Part B. All patients received imipenem/cilastatin as background therapy. The primary safety objective was nephrotoxicity (RIFLE classification); other safety endpoints included treatment-emergent adverse events (TEAEs) and assessments of laboratory parameters.

Results
The safety population includes 203 unique patients. TEAEs were common reflecting the critical level of illness. More frequently reported with colistin treatment are severe, serious, and drug-related TEAEs (infections, renal and urinary disorders, and gastrointestinal) (Table 1). Nervous system, infections and renal disorders leading to discontinuation of study drug were more common in the colistin arm (Table 2). During treatment, liver-associated enzymes were similar between arms. Creatinine clearance measures of central tendency showed reduction during the trial in the colistin arm. Nephrotoxicity (RIFLE classification) occurred significantly less often with SUL-DUR: 13.2% (12/91) and 37.6% (32/85), difference -24.4% [p=0.0002].

Conclusion
SUL-DUR treated patients had reduced nephrotoxicity, fewer drug-related TEAEs, no safety signals, and fewer TEAEs leading to discontinuation of study drug. If approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains.

Disclosures
Drew Lewis, MD, MTM&H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.
889. Another Respiratory Culture Nudge Improves Pneumonia Prescribing
Authors: Langley Christen , Kenney Rachel M , Kendall Ronald , Tibbetts Robert , Veve Michael 
Published: December 2022

Abstract

Background
Nudging with purposeful, directed comments to microbiology results appears to improve antibiotic prescribing. The study objective was to assess prescribing before and after a β-lactamase interpretative comment for Haemophilus influenzae and Moraxella catarrhalis lower respiratory tract infections (LRTI).

Methods
IRB approved, quasi-experiment. Included: hospitalized adults prescribed antibiotics for H. influenzae or M. catarrhalis LRTI from 8/20/17-3/19/19 (pre-group) and 3/20/19-8/20/21 (post-group). Excluded: non-LRTI, polymicrobial infections, antibiotic prophylaxis, IgE-mediated β-lactam allergy. Intervention- automated comment for β-lactamase negative: “this organism is predictably susceptible to ampicillin or amoxicillin”; β-lactamase positive: “this organism is predictably susceptible to ampicillin-sulbactam or amoxicillin-clavulanate”. Primary endpoint: optimal de-escalation, defined as ampicillin, amoxicillin or aminopenicillins for β-lactamase negative; amoxicillin/clavulanate or ampicillin/sulbactam for β-lactamase positive. Secondary endpoints: clinical success, antibiotic duration, time to de-escalation. Sample size: 200 calculated for 30% difference in de-escalation, α=0.05, β=0.2.

Results
Enrolled 100 pre- and 101 post. 61% vs. 64% male; 63% vs. 73% community-acquired pneumonia; 20% vs. 15% hospital acquired pneumonia; 17% vs. 12% ventilator associated pneumonia; 81% vs. 77% H. influenzae; 46% vs. 52% β-lactamase positive; 4% vs. 7% non-IgE β-lactam allergy, respectively. Optimal de-escalation: 19 (19%) pre-, 51 (51%) post- (p&lt; 0.001). After adjustment, post-group associated with 5-fold increased odds of optimal de-escalation (Table 1). Secondary endpoints pre and post: median (IQR) duration 7 (6, 8) and 7 days (6, 10); median time to de-escalation: 1 (0, 2) and 0 (0, 1) days; clinical success: 79 (79%) and 81 (80%).

Conclusion
An automated, β-lactamase nudge was associated with a reduction in definitive broad-spectrum antibiotics. Stewardship programs should continue to evaluate persuasive comments as an effective and efficient intervention.

Disclosures
All Authors: No reported disclosures.
901. Evaluation of Azithromycin Usage Following a Pharmacist Discontinuation Protocol
Authors: Percival Kelly M , Kinn Patrick M , Weiner Lukasz , Ince Dilek 
Published: December 2022

Abstract

Background
Azithromycin usage along with a beta-lactam is common in hospitalized patients with community-acquired pneumonia (CAP). The total recommended dosage is 1500mg as either 500mg on day one followed by 250mg daily for 4 days or 500mg daily for 3 days. It was observed that total doses of &gt;1500mg were frequently administered at our institution. Institutional empiric treatment guidelines for CAP were updated and educational sessions were given for medicine providers in November 2019 to emphasize a total dose of 1500mg. This was further followed in April 2020 by the creation of a pharmacist collaborative practice agreement (CPA) to allow any unit-based clinical pharmacist to discontinue azithromycin for CAP after administration of a sum total of 1500mg.

Methods
A retrospective quasi experimental study was performed to evaluate the impact of implementing a pharmacist CPA for discontinuation of azithromycin for CAP. The primary objective was to compare the proportion of patients receiving greater than 1500mg of azithromycin during the pre-implementation period of April 2018-March 2020 to the post-implementation period of April 2020-March 2022. Pre- and post-implementation period rates were compared using a Chi-square test. Secondarily, utilization of CPA as the discontinuation method was evaluated.

Results
A total of 8,373 patients were included (5123 pre and 3250 post) in the analysis. The proportion of patients receiving &gt;1500mg of azithromycin decreased from 29.32% pre-implementation to 20.22% post-implementation (P&lt; 0.001). There was a decrease seen immediately after implementation that has been maintained over time, as shown in figure 1. The CPA was utilized for discontinuation in a minority of patients during the post-implementation period and the majority discontinued by pharmacists were per verbal order.
Percentage of Patients Receiving &gt;1500mg Azithromycin

Conclusion
Implementation of a pharmacist driven CPA for discontinuation of azithromycin for CAP reduced excessive azithromycin usage with minimal time burden for the AMS team. To further meet the goal of decreasing excessive azithromycin usage additional interventions are needed, and low utilization of the CPA should be further evaluated.

Disclosures
Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant Patrick M. Kinn, PharmD, MPH, Gilead Sciences: Advisor/Consultant Dilek Ince, MD, Evergreen: Member of data monitoring board|Gilead Sciences: Grant/Research Support|Leidos: Grant/Research Support|Moderna: Grant/Research Support.
902. Evaluation of Post-Discharge Sterile-Site Positive Microbiology Results and the Impacts on Patient Care
Authors: LaPlante Reid L , Claeys Kimberly C , BORK J A C Q U E L I N E T , Banoub Mary , Noval Mandee 
Published: December 2022

Abstract

Background
Half of patients have cultures pending at discharge. Failure to address these results may delay diagnosis and time to appropriate antimicrobials. The purpose of the study is to evaluate appropriateness of antimicrobial therapy and result documentation in patients with positive cultures finalized post-discharge.

Methods
Retrospective cohort study of patients from 7/2019-12/2019 with positive sterile-site microbiologic cultures finalized post-discharge. Pertinent inclusion and exclusion factors were admission ≥48 hours and non-sterile sites, respectively. The primary objective was to determine the frequency of discharged patients warranting antimicrobial intervention based on finalized culture results. Secondary objectives included incidence and timeliness of result documentation and rates of 30-day hospital readmission, among intervention warranted vs not warranted. Chi-squared or Fisher’s exact tests were used as appropriate. Binary multivariable logistic regression was completed for 30-day hospital re-admission stratified by infectious disease (ID) team involvement.

Results
208 of 768 patients screened were included. Most patients were discharged from a surgical service (45.7%); deep tissue and blood were the most common culture sites (29.3%). Antimicrobial intervention was warranted in 36.5% of patients (n=76). Rates of result documentation were overall low (35.5%). Time to documentation of results was significantly shorter in patients warranting intervention compared to those who did not, but hospital readmission was higher (Table 1). Finally, result documentation in patients not being followed by ID was associated with decreased odds of 30-day readmission (OR 0.19, 95% CI, 0.07-0.53) (Table 2).

Conclusion
A significant number of patients with cultures finalized post-discharge warranted antimicrobial intervention. Acknowledgment of final culture data can decrease the risk of 30-day hospital readmission, especially in patients not followed by ID. Quality improvement efforts should focus on methods to improve documentation and follow-up of pending cultures to improve patient outcomes.

Disclosures
Kimberly C. Claeys, PharmD, BioFire Diagnostics: Honoraria|La Jolla Pharmaceuticals: Advisor/Consultant.
910. Impact of Indication-based Antibiotic Order Sentences on Optimal Prescribing in the Emergency Department: A Quasi-experiment
Authors: Vuong Lisa , Kenney Rachel M , Thomson Julie , Faison Darius J , Veve Michael P 
Published: December 2022

Abstract

Background
A prior study demonstrated suboptimal antibiotic prescribing in the emergency department (ED) at 77.4% for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections (UTI), and acute bacterial skin and skin structure infections (ABSSSI). This study measured the effect of indication-based antibiotic order sentences (AOS) on prescribing.

Methods
IRB-approved quasi-experiment of adults prescribed antibiotics in ED for uncomplicated LRTI, UTI, or ABSSSI from January - June 2019 (pre-group) or September - December 2021 (post-group). Exclusion: hospital admission, immunocompromised, active cancer, or prophylactic antibiotics. AOS are lean process, electronic discharge prescriptions retrievable by name or indication; AOS implementation occurred July 2021. Optimal prescribing was defined as the correct antibiotic selection, dose, and duration per local and national guidelines. Seven-day endpoints: antibiotic escalation, ED or hospital readmission, any outpatient contact, and reported adverse drug event (ADE). Descriptive and bivariate statistics performed. Variables considered for multivariable logistic regression had p&lt; 0.2 or plausible association with optimal prescribing.

Results
294 patients included: 147-pre and 147-post. Patient characteristics are in Table 1. Overall optimal prescribing improved from 12 (8.2%) to 34 (23.1%) (p&lt; 0.001). Breakdown of optimal prescribing in pre- and post-groups: selection 90 (61.2%) vs 117 (79.6%) (p&lt; 0.001), dose 99 (67.3%) vs 115 (78.2%) (p=0.036), duration 38 (25.9%) vs 50 (34%) (p=0.126). After adjustment, AOS were independently associated with optimal prescribing (Table 2). Secondary endpoints: antibiotic escalation 10 (6.8%) vs 7 (4.8%) (p=0.662), hospital or ED readmission 12 (8.2%) vs 10 (6.8%) (p=0.658), outpatient contact 31 (21.1%) vs 28 (19%) (p=0.662), and ADE 2 (1.4%) vs 4 (2.7%) (p=0.684). Post-hoc analysis showed suboptimal uptake of AOS by ED prescribers. Table 1:Baseline and Clinical CharacteristicsTable 2:Bivariable and Multivariable Regression Analysis of Factors Associated with Optimal Prescribing†Covaries with intervention group; Hosmer and Lemeshow p = 0.68; Method: backwards logistic regression; No variables removed

Conclusion
AOS is an efficient and promising antimicrobial stewardship strategy; provider re-education is needed to increase AOS uptake.

Disclosures
All Authors: No reported disclosures.
913. Impact of BioFire® FilmArray® Blood Culture Identification Panels on Time to Optimal Antimicrobial Therapy
Authors: Vyas Shivam , Giordano Pamela , Patel Dimple , Bandali Aiman 
Published: December 2022

Abstract

Background
Bloodstream infections are associated with significant morbidity, mortality, and costs. Timely initiation of effective treatment is required for optimal outcomes. Conventional microbiological techniques require 72 hours for organism identification; however, rapid blood culture identification (BCID) polymerase chain reaction (PCR) panels have expedited this process. At Atlantic Health System, the BioFire® FilmArray® BCID panel was implemented June 2020 (BCID1), with subsequent upgrade to BCID2 March 2021. Notable features of the BCID2 panel include speciation of Enterococcus spp. and the addition of the CTX-M target. The purpose of this study is to assess time to optimal therapy (TTOT) with and without the BCID platforms for select organisms. Table 1:Select Primary and Secondary Endpoints

Methods
This retrospective study of hospitalized, adult patients was conducted at two community teaching hospitals from 5/2019 to 12/2021. Patients with a blood culture positive for Enterococcus faecalis, E. faecium, Proteus spp., Escherichia coli, or non-aerogenes Klebsiella spp. were included. Patients with polymicrobial or presumed polymicrobial source of bacteremia, recent positive blood cultures, PCR not performed in BCID arms, or who were deceased/comfort care at time of Gram stain were excluded. The primary endpoint was TTOT. Secondary endpoints included time to effective therapy, duration of vancomycin, therapy modification 24 hours after Gram stain result, and length of stay. All analyses compared PreBCID to either BCID1 or BCID2 arm.

Results
Three hundred patients (100 per arm) were included. Patient characteristics were similar across study arms. The median Pitt Bacteremia Score was 1, the most common organism identified was E. coli (65%), the most common source of bacteremia was genitourinary (65%), and 11% of isolates produced ESBL. TTOT (days) was similar in PreBCID compared to BCID1 and BCID2 [(2.48 vs. 2.65, p=0.10); (2.48 vs. 2.37 days, p=0.27)]. TTOT was significantly longer in the gram-negative subgroup of the BCID1 arm compared to PreBCID (2.62 vs 1.85 days, p=0.03). See Table 1 for full analyses.

Conclusion
Implementation of the BCID panels did not reduce TTOT in select organisms at our institution. Barriers to benefit may include limited education and lack of formal antimicrobial stewardship team involvement.

Disclosures
All Authors: No reported disclosures.
917. Infectious Diseases Consult Improves Management of Candidemia
Authors: Stornelli Nick , Everson Nathan , Everson Nathan , Everson Nathan , McDaniel Lauren , White Melissa 
Published: December 2022

Abstract

Background
Infectious Diseases consultations (IDC) have been associated with improved outcomes in multiple disease states with high morbidity/mortality like invasive candidiasis. This study evaluated management of candidemia at Carilion Clinic in patient with and without IDC.

Methods
A retrospective, observational cohort study was performed among hospitalized patients with candidemia who either received or did not receive an IDC between January 2014 and August 2020. Patients included had Candida species from at least one blood culture. Exclusions were death or transfer to a palliative care plan within 48 hours of culture, cultures from an outside facility, and patients that were pregnant or incarcerated. The primary outcome was a composite of all-cause mortality and recurrent candidemia within 90 days. Secondary outcomes included compliance with candidemia management bundle items such as echocardiography, ophthalmologic evaluation, receipt of susceptible antifungal, source control and repeated blood cultures.

Results
A total of 194 patients were included in the study. The population was 50.3% male sex and mean ± standard deviation age was 57.8 ± 17.2 years. In the study timeframe, 131 patients received an IDC while 62 did not receive an IDC. ICU level of care, vasopressor requirement and Candida Score ≥ 3 were all similar between the two groups. Candida albicans was the most common species in IDC and non-IDC groups (48.1% vs. 41.1%). Empiric therapy was more commonly an echinocandin in 138/194 (71.1%) and definitive therapy was fluconazole in 117/194 (60.3%). An improved primary composite outcome was observed in the IDC group (34.9% vs. 21.4%, p = 0.043). Patients receiving IDC had a higher rate of repeated cultures (100% vs. 92%) and ophthalmologic examination (54.2% vs. 20.6%). More patients in the IDC group were found to have infective endocarditis (10.7% vs. 1.6%, p = 0.04) as they were more likely to have echocardiographic imaging (86.2% vs. 57.1%, p&lt; 0.0001). The median time to susceptible antifungal was 43 (27-61) hours without ICD and 35 (27-52) hours compared in those with IDC.

Conclusion
A more comprehensive workup by IDC was associated with more identification of endocarditis and less recurrence of candidemia within 90 days.

Disclosures
Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Lauren McDaniel, PharmD, BCIDP, Merck: Grant/Research Support.
921. Leveraging the Electronic Health Record for Antimicrobial Stewardship: Assessing the Impact of Antimicrobial Ordering Clinical Decision Support Tools on Duration of Therapy
Authors: Gerhardt Jenna , Cheatham Megan , Davis Christie M , Dine Serena , Erdman Sharon , Geik Katherine , Gerke Steven , Kressel Amy B , McIntire Allyson 
Published: December 2022

Abstract

Background
In an ideal state, the stewardship of antimicrobial agents would happen at the point of order entry. In June 2018, Eskenazi Health implemented a series of clinical decision support tools in the electronic health record (EHR), including required fields on all inpatient antimicrobial orders for indication, type of therapy (empiric or definitive), and duration. When empiric therapy is selected, providers receive a Best Practice Advisory (BPA) at 48 hours to re-evaluate therapy. Additionally, a side bar table was added to all antimicrobials orders that included drug-specific duration of therapy recommendations for common indications.

Methods
This is a single-center, retrospective, observational chart review that includes adult inpatients prescribed antibiotics for the treatment of CAP or UTI from July 2017 to December 2018. The primary outcome is the overall length of therapy between pre- and post-intervention groups for CAP and UTI. Secondary outcomes include duration of empiric/broad-spectrum therapy, duration of definitive therapy, time to de-escalation, length of hospital stay, C. difficile infections, 30-day readmission, and cost of antimicrobial therapy.

Results
A total of 541 orders were included for analysis. The composite overall duration of therapy decreased from 7 days to 5 days in the post-intervention group (p&lt; 0.001). For CAP, the duration of therapy (5 days) was not different between groups. For UTI, the duration of therapy decreased from 11 days to 7 days in the post-intervention group (p&lt; 0.001). The duration of empiric therapy decreased from 3 days to 2 days (p&lt; 0.001) and the duration of definitive therapy decreased from 4 days to 3 days (p&lt; 0.001). There was a 1 day longer length of stay for patients in the post-intervention group (p=0.038); however, there was a lower 30-day readmission rate in the post-intervention group (p=0.003). The rate of hospital-acquired C. difficile infections did not differ between groups (p=1.000). It was found that action was taken from the BPA 55.4% of the time after implementation.

Conclusion
The duration of therapy overall was shortened by 2 days, which was driven by the difference in duration for UTI. Incorporating antimicrobial stewardship principles at the point of order entry can result in fewer days of unnecessary therapy.

Disclosures
All Authors: No reported disclosures.
923. Providers’ Perception of CME Antimicrobial Stewardship Quizzes and Its Impact on Antibiotic Prescribing Practices
Authors: Chan Shannon , Harrington Nicole , Couch Kimberly A , Marcinak Rebecca , Shapiro Craig , Chasanov William M , Dressler Robert , Consiglio-Ward Loretta , Drees Marci 
Published: December 2022

Abstract

Background
A statewide antimicrobial stewardship (AS) collaborative across 5 health systems was formed with the mission to share best antibiotic prescribing. Recognizing that education is an important pillar of AS intervention, the statewide collaborative implemented a monthly CME quiz focusing on a wide range of clinical infectious diseases and AS topics. These quizzes consisted of 5-10 case-based and clinical pearl questions with evidence-based answers focusing on the adult and pediatric patient populations. Participants were awarded one hour CME credit. After 3 years of distributing the quizzes, we sought to assess the providers’ perceptions of the CME quizzes and their impact on clinical practice.

Methods
A nine-question survey was emailed to providers, pharmacists, and nurses. Questions regarding providers’ perceptions on the importance of antibiotic education and the impact that it has on their clinical practice were included.

Results
Among the 89 respondents, 50% were physicians, 25.6% were advanced practice providers, 14% were pharmacists and 3.5% were nurses. The most common practice setting was primary care (43.8%), followed by acute care (35.9%). The monthly ASP quizzes were considered helpful or very helpful in enhancing their practice in 95% of the respondents. More than half of the respondents believed that the ASP quizzes led to enhancement of their ASP knowledge (61.8%). Prescribing shorter duration and narrow spectrum antibiotic were reported by 48 (53.9%) and 28 (31.5%) respondents respectively. Twenty-three (25.8%) respondents reported that they prescribe less antibiotics because of the ASP quizzes and 28 (31.5%) reported that they became more aware of potential harm of antibiotics. The ASP quizzes did not influence, but rather reinforce current prescribing practice in 25% of the respondents.

Conclusion
Provider directed education is a core element of both ambulatory and acute care antimicrobial stewardship. Through a statewide initiative, using a monthly CME quiz circulated via email, prescribers were able to improve their knowledge and enhance their prescribing of antibiotics. Most providers perceive this format of education as helpful and describe it as having a positive impact on their prescribing behavior.

Disclosures
All Authors: No reported disclosures.