bluuebunny/crossref_metadata_2025_split huggingface dataset:
751. Study on Daptomycin Prescription Suitability as a First Step Towards an Antimicrobial Stewardship Program
Authors: Sánchez Sebastián García , Moreno Félix Jesús García , de Vega Esther Chamorro , Minero Maricela Valerio , González Carmen Guadalupe Rodríguez , Galar Alicia , Samperio María Olmedo , Machado Marina , Pedromingo Miguel , García-Paredes Patricia Muñoz , Bouza Emilio , Sáez María Sanjurjo 
Published: October 2019

Abstract

Background
Daptomycin use has increased since its approval and has often extended to indications not included in the summary of product characteristics with highly variable dosing. Our objective was to assess daptomycin real use in an institution with Pharmacy and ID consultation available and to explore the need for establish specific Daptomycin stewardship.

Methods
Observational, retrospective study including all patients treated with daptomycin during 2017 in a tertiary hospital. Clinical variables were collected in a pre-established protocol including demographics, comorbidities, infection type, microbiological results, adverse events (AE), outcomes, and treatment adequacy (selection, dosage, microbiological adjustment and duration). Daptomycin prescription is not restricted at our institution. The dosages were considered adequate according to clinical guidelines.

Results
Overall 176 patients (62% men, median age: 70years) started treatment with daptomycin, 58% of them on empirical bases. Main uses were: skin and soft-tissue infections (37.5%), fever without obvious source (17.6%) and osteoarticular infection (12.5%). Sixty-three patients (35.8%) had concomitant bacteremia. An etiologic diagnosis was reached in 89.2% patients and S.aureuswas the most frequently isolated microorganism (n = 58, and 10 MRSA), followed by CoNS (n = 35). Overall, 77.7% of patients evolved satisfactorily. Five patients discontinued treatment due to AE (urticaria, cholestasis, increased CPK and rhabdomyolysis). Infection-related mortality was 7.4%. Daptomycin was correctly selected in 94.3% patients, length of therapy was adequate in 87.4%. However, only 47.1% of patients received adequate dosage (underdosing in 27.8%) and in 9.8% of patients, the treatment was not adjusted according to microbiological results. The prevalence of daptomycin use was 3.7 patients/1,000 admissions.

Conclusion
Daptomycin is often prescribed empirically, using nonadequate dosages and duration of therapy needs also an improvement. The follow-up of patients treated with daptomycin should be considered a priority intervention within an Antimicrobial Stewardship Program.

Disclosures
All authors: No reported disclosures.
770. Multimodal Sepsis Performance Improvement Initiative Improves Early and Appropriate Treatment, Reduces Sepsis-related Readmissions, and Reduces Overall Mortality
Authors: Yohannes Seife 
Published: October 2019

Abstract

Background
CMS has implemented the SEP-1 Core Measure, which mandates that hospitals implement sepsis quality improvement initiatives. At our hospital, a 900-bed tertiary hospital, a sepsis performance improvement initiative was implemented in April 2016. In this study, we analyzed patient outcomes before and after these interventions.

Methods
We studied coding data in patients with a diagnosis of Sepsis reported to CMS using a third-party performance improvement database between October, 2015 and July, 2017. The interventions included a hospital-wide education campaign about sepsis; a 24–7 electronic warning system (EWS) using SIRS criteria; a rapid response nursing team that monitors the EWS; a 24–7 mid-level provider team; a database to monitor compliance and timely treatment; and education in sepsis documentation and coding. We performed a before and after analysis of patient outcomes.

Results
A total of 4,102 patients were diagnosed with sepsis during the study period. 861 (21%) were diagnosed during the pre-intervention period and 3,241 (80%) were diagnosed in the post-intervention period. The overall incidence of sepsis, severe sepsis, and septic shock were 59%, 13%, and 28% consecutively. Regression analysis showed age, admission through the ED, and severity of illness as independent risk factors for increased mortality. Adjusted for these risk factors, the incidence of severe sepsis and septic was reduced by 5.3% and 6.9% in the post-intervention period, while the incidence of simple sepsis increased by 12%. In the post-intervention period, compliance with all 6 CMS mandated sepsis bundle interventions improved from 11% to 37% (P = 0.01); hospital length of stay was reduced by 1.8 days (P = 0.05); length of stay above predicted was less by 1.5 days (P = 0.05); re-admission rate was reduced by 1.6% (P = 0.05); and death from any sepsis diagnosis was reduced 4.5% (P = 0.01). Based on an average of 2000 sepsis cases at our hospital, this amounted to 90 lives saved per year. Death from severe sepsis and septic shock both were also reduced by 5% (P = 0.01) and 6.5% (P = 0.01).

Conclusion
A multi-modal sepsis performance improvement initiative reduced the incidence of severe sepsis and septic shock, reduced hospital length of stay, reduced readmission rates, and reduced all-cause mortality.

Disclosures
All authors: No reported disclosures.
997. Practical partnering of Antibiotic Stewardship and Allergy to address referrals to Penicillin allergy debunking clinic at a VA Medical Center
Authors: Sheth Dipa , Adenew Ayne , Charya Raghava , Santelices Judy , Liappis Angelike P 
Published: October 2019

Abstract

Background
The majority of Penicillin (PCN) allergies can be “debunked.” During acute medical care, opportunities to refer for formal evaluation are often overlooked, hampered by medication-interactions and lack of time and resources for bedside testing. Frequently, inpatients are not referred for PCN debunking evaluations (PCN-DE). Antimicrobial Stewardship Teams (ASTs) who partner with Allergy Clinical Teams (ACTs) can work collaboratively to target those who would benefit from de-labeling and are unlikely to otherwise be referred for formal evaluation.

Methods
The DCVAMC is an urban 240 bed 1a complexity acute and LTC teaching hospital with both on-site AST and well-established ACT. β-lactam allergy was tracked by the AST in inpatient, outpatient and long-term care setting utilizing a clinical surveillance system (TheraDoc, DSS Inc.) and allergy education was incorporated into prospective auditing rounds. PCN-DE involved face-face visit with an Allergist and careful history, chart/medication review. Option for skin testing (Pre-Pen, ALK Abello) with/without oral challenge performed at the discretion of ACT. EMR was altered to reflect results.

Results
We collaborated to develop a PCN-DE outpatient Allergy Clinic on the hospital campus. 2,564 designed β-lactam allergy alerts were identified as part of routine AST workflow prior to the initiation of the clinic in October 2017. Referrals resulted from AST prospective audits, consults to ACT and by surveillance of historical allergy history among acute and LTC admissions. Providers, including trainees, were engaged through education and encouraged to place outpatient referrals at the time of discharge or upon follow-up. ACT evaluated patients in groups of 2–3/session, roughly one clinic/month. Mean age of patients tested 56.3y (24–80y) with 35% >65yo; to date, (19/26) 73% have been successfully de-labeled

Conclusion
The success in de-labeling after formal evaluation is well established. Developing working relationships with allergists and encouraging providers to recognize often overlooked opportunities to refer to existing or newly established clinics is easily adopted by ASTs. In conjunction with screening, targeted education and referral to PCN-DE as a part of routine stewardship workflow has practical and immediate benefits.

Disclosures
All authors: No reported disclosures.
1046. Evaluating the outcomes of embedding Antimicrobial Stewardship order sets in the General Medicine Admission Electronic Order Set: A Retrospective Study
Authors: Chan April , Kapur Ajay , Langford Bradley , Downing Mark 
Published: October 2019

Abstract

Background
The use of facility-specific guidelines and clinical decision-making tools are recommended by a number of organizations to improve the appropriateness of empiric antimicrobial prescribing; however, how to increase usage is not clear. We evaluated the impact of embedding antimicrobial stewardship (AS) electronic order sets (EOS) into the general medicine admission EOS in the context of an established AS program.

Methods
The standalone EOS for community-acquired pneumonia (CAP), urinary tract infection (UTI) and cellulitis were reviewed and simplified to only include the antibiotic section prior to embedding. The intervention was introduced on March 30, 2017 with pre-intervention period defined as January 1, 2016 to March 29, 2017 and post-intervention period as of March 30, 2017 to June 30, 2018. The primary outcome was the change in usage of embedded AS EOS compared with the corresponding standalone EOS using counts. In addition, other standalone AS EOS (i.e., Clostridioides difficile infection (CDI), etc) were used as a control. The secondary outcomes were the change in antibiotic usage de-emphasized in embedded EOS (i.e., ceftriaxone, ciprofloxacin, clindamycin, moxifloxacin) and predicted prescribing shifts to antibiotics in the embedded EOS (i.e., amoxicillin-clavulanate, azithromycin and sulfamethoxazole-trimethoprim) using Days of Therapy (DOT)/1000 patient-days (PD). Paired t-test was used to compare antibiotic usage pre- and post-intervention.

Results
The usage of standalone EOS remained similar pre- and post-intervention except for a 16-fold increased usage of CDI EOS. There were large increases in uptake of the embedded EOS compared with the standalone EOS: 11-fold () increase for CAP, 47-fold () increase for UTI and 24-fold () increase for cellulitis. In addition, there was a statistically significant decrease in ciprofloxacin (mean 16.6 DOT/1000-PD vs. 13.6 DOT/1000-PD, P = 0.026) and moxifloxacin usage (mean 9.3 DOT/1000-PD vs. 5.2 DOT/1000-PD) during the study time period.

Conclusion
Our study showed that simplifying AS EOS and embedding these into a more commonly used EOS is associated with a significant increase in EOS usage and uptake of AS recommended empiric antibiotics with a decrease in fluoroquinolone usage.

Disclosures
All authors: No reported disclosures.
1048. A Randomized Controlled Trial of an Electronic Tool for Empiric Antibiotic Prescription: Results from the ANti-infective Stewardship using the WISCA tool in the Electronic Medical Record (AnSWER) Study
Authors: Ridgway Jessica , Shah Nirav , Ellen Acree Mary , Semel Jeffrey , Datta Avisek , Singh Kamaljit , Peterson Lance 
Published: October 2019

Abstract

Background
The Weighted-Incidence Syndromic Combination Antibiogram (WISCA) is a computer-based, clinical tool for improving initial antibiotic selection in the management of pneumonia, cellulitis, urinary tract infection (UTI) and intraabdominal infection (IAB). WISCA predicts the likelihood that an antibiotic regimen will be active against the expected organisms causing the infection for each of these syndromes.

Methods
We performed a crossover randomized controlled trial of the WISCA tool between July 1, 2015 and June 30, 2018 at 4 hospitals. WISCA suggests an empiric antibiotic regimen based on individual patients’ comorbidities, severity of illness, allergy profile, history of multidrug-resistant organisms (MDRO), and prior antibiotics. Within 24 hours of admission an ID physician-reviewed patient charts to determine whether one of the clinical syndromes was present. At intervention hospitals, patients’ providers were notified when a change in empiric therapy was suggested or antibiotics were recommended to be stopped (if no bacterial infection was present). Outcomes included readmission, mortality, C. difficile infection (CDI), MDRO infection, length of stay (LOS), and cost of antibiotics.

Results
10,202 patients enrolled in the study with 4,451 (57% female, mean age 72) in the intervention arm and 5,751 (55% female, mean age 71) in the control arm. There were no significant differences in clinical outcomes for any of the syndromes. Among 2,146 patients determined to have no bacterial infection, WISCA intervention resulted in lower antibiotic cost during the hospital stay ($714.46 vs. $927.56, P < 0.01). When providers accepted the recommendation to stop antibiotics, there were fewer antibiotic days (mean 296 antibiotic days/1000 patient-days vs. mean 378 antibiotic days/1000 patient-days, P = 0.038) and no significant difference in mortality or readmission rates. No bacterial infection patients also experienced a nearly 3-fold lower rate of CDI vs. patients with infection (0.8% vs. 2.3%, P < 0.001).

Conclusion
Although the use of the WISCA tool was not associated with a reduction in mortality, readmissions, or LOS, intervention to stop antibiotics for those with no bacterial infection was associated with reduced antibiotic use and cost savings.

Disclosures
All authors: No reported disclosures.
1065. Keeping Score: Utilizing a Prioritization Tool to Create Multidisciplinary Antimicrobial Stewardship Documentation
Authors: Mediwala Krutika N , Raux Brian R , Philip Acshah , Parks Amanda , Dixon Terry , Gnann John W 
Published: October 2019

Abstract

Background
A multidisciplinary approach using pre-authorization and/or prospective audit and feedback combined with institutional guidelines, personnel education, and intervention monitoring is essential for successful antimicrobial stewardship programs (ASP). Assessing the impact of ASPs can be process-based and/or outcome-based. Electronic medical record-based clinical decision support (CDS) tools can be used to prioritize stewardship interventions.

Methods
The Medical University of South Carolina (MUSC) transitioned from Theradoc® to Epic® for ASP surveillance and data collection in 2018. The ASP team developed a scoring algorithm with integral rules to identify and analyze inpatients who might require ASP interventions. The dynamic list captures and scores patients based on key infection-related data and prioritizes interventions. Additionally, we created a smart form flowsheet to streamline stewardship efforts for use by physicians and pharmacists. Accuracy of event capture was assessed during the buildout and via daily comparisons between Theradoc® and Epic®. Our goals are to optimize the treatment of potentially fatal infections (e.g., bacteremia) and delay emerging resistance.

Results
Our ASP module utilizes a scoring algorithm to identify and prioritize patients with positive blood or central nervous system cultures, other positive critical diagnostic tests, and high-risk antimicrobial use. Additional rules identify “bug-drug” mismatches, multiple positive cultures, and de-escalation opportunities. For example, the rules assign a high priority to patients with positive blood cultures and no prescribed antibiotics, but a lower priority score to restricted antimicrobial orders. We created a smart form flowsheet to document microorganism, presumed source, anti-infective use, ASP intervention, and acceptance of recommendations, allowing for multidisciplinary documentation outside of Epic® I-vents. Finally, we created a Reporting Workbench report which allows for monthly compilation and analysis of ASP interventions.

Conclusion
The MUSC Epic® ASP platform build showcases a CDS system that allows for streamlined, multidisciplinary communication, documentation, and analysis of outcomes.

Disclosures
All authors: No reported disclosures.
1115. Reducing Broad-Spectrum Antibiotics for Uncomplicated Urinary Tract Infections: A Multimodal Stewardship Intervention
Authors: Laguio-Vila Maryrose R , Staicu Mary L , Lourdes Brundige Mary , Alcantara-Contreras Jose , Yang Hongmei , Lautenbach Ebbing , Dumyati Ghinwa 
Published: October 2019

Abstract

Background
Urinary tract infections (UTIs) are the second most common reason for antibiotics in hospitalized patients, with most receiving broad-spectrum antibiotics (BSA) regardless of infection severity. The antimicrobial stewardship program (ASP) conducted a multimodal stewardship intervention targeting reduction in one BSA, ceftriaxone, and promoted narrow-spectrum antibiotics (NSA) such as cefazolin and cephalexin for uncomplicated UTIs.

Methods
Phase 1: In February 2018, the ASP created a pocket card (Figure 1) containing (1) a urinary antibiogram outlining the most common urine pathogens and their local susceptibility to NSA and (2) NSA guidelines for UTIs with 0–1 systemic inflammatory response syndrome (SIRS) criteria. ASP performed a daily prospective audit with feedback on all new orders of ceftriaxone and promoted prescription of NSA. Phase 2: In August 2018, a Best Practice Alert (BPA) in the electronic medical record (EMR) was designed to interrupt providers ordering ceftriaxone with the indication of a UTI, and prompted NSA prescription instead. Quarterly didactic sessions on UTI antibiotic use and BPA functionality were done. We compared antibiotics usage rates across the 3 study phases (pre-intervention, phase I and phase II) by computing rate ratios (RRs) using Poisson regression.

Results
Compared with pre-intervention, phase 1 resulted in a significant decrease in ceftriaxone DOT (RR: 1.06, CI: 1.03–1.09, P < 0.001) and ceftriaxone orders for UTI (RR: 1.14, P < 0.001) and an increase in cefazolin DOT (RR: 0.89, P = 0.029) and orders for UTI (RR; 0.12, P < 0.001). It also resulted in a significant increase in cephalexin DOT (RR: 0.92, P = 0.002) and orders for UTI (RR: 0.58, P < 0.001). In phase 2, an additional significant reduction in ceftriaxone DOT (RR: 1.04, CI: 1.01–1.08, P = 0.018) and orders for UTI (RR: 1.62, P < 0.001) and an increase in cefazolin DOT (RR: 0.96, P < 0.001) and orders for UTI (RR; 0.56, P < 0.001) occurred, when comparing phase I to phase 2. It also resulted in a decrease in cephalexin DOT (RR: 0.83, P < 0.001) and orders for UTI (RR: 0.70, P < 0.001).

Conclusion
A multimodal stewardship intervention using a pocket card with guidelines and urine antibiogram, and an EMR BPA successfully reduced BSA and increased NSA for treatment of uncomplicated UTIs.

Disclosures
All authors: No reported disclosures.
LB2. TORC1 Inhibition with RTB101 as a Potential Pan-Antiviral Immunotherapy to Decrease the Incidence of Respiratory Tract Infections Due to Multiple Respiratory Viruses in Older Adults
Authors: Mannick Joan , Tomlinson Amelia , Shergill Sarb , Teo Grace , Klickstein Lloyd 
Published: October 2019

Abstract

Background
Respiratory tract infections (RTIs) are a leading cause of hospitalization and death in people age ≥65 years. RTIs are caused by multiple viruses, most of which lack effective treatments. An immunotherapy that enhances pan-antiviral innate immunity may reduce RTI incidence in older adults. Inhibition of targets downstream of target of rapamycin complex 1 (TORC1) was reported to upregulate pan-antiviral gene expression and protect mice from a viral RTI (York AG et al. Cell 2015). We evaluated whether TORC1 inhibition increased antiviral gene expression and decreased RTI incidence in older adults.

Methods
A randomized, double-blind, placebo, controlled study was conducted to determine whether the TORC1 inhibitor RTB101 alone or in combination with the TORC1 inhibitor everolimus reduced the incidence of laboratory-confirmed RTIs. The study enrolled 652 older adults at increased risk of RTI-related morbidity and mortality (defined as age ≥85 years, or age ≥65 years with asthma, COPD, type 2 diabetes mellitus, or current smokers). Subjects were treated for 16 weeks during winter cold and flu season with oral RTB101 5 mg or 10 mg once daily (QD), RTB101 10 mg twice daily, RTB101 10 mg + everolimus 0.1 mg QD, or matched placebo. The primary endpoint was the percentage of subjects with ≥1 laboratory-confirmed RTI through Week 16.

Results
RTB101 was well tolerated. In the intent-to-treat analysis, RTB101 10 mg QD was observed to: reduce the percentage of subjects with laboratory-confirmed RTIs by 30.6% compared with placebo (P = 0.025); reduce the incidence of RTIs caused by multiple different viruses; and upregulate interferon-stimulated pan-antiviral gene expression in whole blood (P = 0.00001 vs. placebo, Figure 1). Furthermore, RTB101 10 mg QD was observed to reduce the time to alleviation of moderate to severe RTI symptoms by 5 days, and to reduce the rate of all-cause hospitalization (rate ratio 0.439, 90% CI 0.196–0.983, P = 0.047).

Conclusion
RTB101 10 mg QD was associated with a significant reduction in laboratory-confirmed RTIs due to multiple viral pathogens that lack effective medicines for treatment or prevention. RTB101 was observed to upregulate interferon-stimulated pan-antiviral gene expression, which may underlie the reduction in RTI incidence.

Disclosures
Joan Mannick, MD, resTORbio (Employee, Shareholder), Amelia Tomlinson, PhD, resTORbio (Employee), Sarb Shergill, PhD, resTORbio (Employee), Grace Teo, PhD, resTORbio (Employee), Lloyd Klickstein, MD, PhD, resTORbio (Employee).
LB4. Efficacy and Safety of Cefiderocol vs. High-Dose Meropenem in Patients with Nosocomial Pneumonia—Results of a Phase 3, Randomized, Multicenter, Double-Blind, Non-Inferiority Study
Authors: Wunderink Richard G , Wunderink Richard G , Matsunaga Yuko , Ari Mari , Ariyasu Mari , Echols Roger , Echols Roger , Menon Anju , Den Nagata Tsutae , Den Nagata Tsutae 
Published: October 2019

Abstract

Background
Cefiderocol (CFDC) is a novel siderophore cephalosporin with activity against a broad range of Gram-negative bacteria. In this study, Day 14 all-cause mortality (ACM) rates were compared between CFDC and meropenem (MEM) in patients with nosocomial Gram-negative pneumonia.

Methods
The study (NCT03032380) was a Phase 3, international, double-blind, randomized, non-inferiority study in hospitalized patients with ventilator-associated, hospital-acquired, or healthcare-associated pneumonia caused by suspected Gram-negative bacteria. Patients were treated with CFDC (2 g, q8h) or MEM (2 g, q8h), both infused for 3 hours, for 7–14 days. Adjunctive linezolid (600 mg, q12h, ≥5 days) was given in both arms to cover Gram-positive bacteria. The primary endpoint was non-inferiority of CFDC to MEM for Day 14 ACM rate in the modified intent-to-treat population (mITT; non-inferiority margin: –12.5%). Key secondary endpoints were clinical and microbiological outcomes at test of cure (TOC), and Day 28 mortality. Safety was investigated up to 28 days after the end of treatment.

Results
In the ITT population, 148 patients were randomized to CFDC and 150 to MEM: 59.7% were ventilated, 32.6% had failure of prior therapy, the median APACHE II score was 15, and 6.0% had concomitant Gram-negative bacteremia at baseline. In the mITT population, non-inferiority of CFDC to MEM for Day 14 ACM was demonstrated; CFDC: 12.4% (18 out of 145 patients) vs. MEM: 11.6% (17 out of 146 patients); treatment difference: 0.8; 95% confidence interval: –6.6; 8.2. Comparable Day 28 ACM (CFDC: 21.0% vs. MEM: 20.5%), clinical cure (CFDC: 64.8% vs. MEM: 66.7%), and microbiological eradication (CFDC: 47.6% vs. MEM: 48.0%) rates were demonstrated in the mITT population at TOC. Clinical cure rates for major target pathogens at TOC were similar between CFDC and MEM arms (figure). The rates of treatment-emergent adverse events (TEAEs), drug-related TEAEs, serious AEs, discontinuation due to TEAEs, and deaths were similar between treatment arms (table).

Conclusion
This study demonstrated the non-inferiority of CFDC to high-dose MEM for the pre-specified endpoint of Day 14 ACM. No unexpected safety signals were observed in the study.

Disclosures
Richard G. Wunderink, MD, Merck (Consultant, Grant/Research Support), Shionogi Inc. (Consultant), Yuko Matsunaga, MD, Shionogi Inc. (Employee), Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee), Roger Echols, MD, Shionogi Inc. (Consultant), Anju Menon, PhD, Shionogi Inc. (Employee), Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee).