bluuebunny/crossref_metadata_2025_split huggingface dataset:
01. Serum Bactericidal Activity Against Circulating and Reference Strains of Meningococcal Serogroup B in the United States: A Review of Meningococcal Serogroup B (MenB) Vaccines in Adolescents and Young Adults
Authors: Coyne-Beasley Tamera , Bocchini Joseph , Cane Alejandro , Burman Cindy , Tort Maria J , Presa Jessica 
Published: December 2021

Abstract

Background
US adolescents and young adults are at particular risk of invasive meningococcal disease (IMD). In 2018, menincococcal serogroup B was responsible for 36% of IMD cases in the US overall and for 66% of cases in adolescents and young adults. This age group is at high risk of IMD during outbreaks, which result in significant response-related costs. MenB vaccine efficacy against IMD relies on its ability to provide broad protection against diverse disease-causing strains. MenB-FHbp (Trumenba) and MenB-4C (Bexsero) are MenB vaccines licensed in the US as 2-dose series with an interval of 6 mo or 1 mo, respectively, recommended in healthy adolescents and young adults. We review available data on vaccine coverage of serogroup B strains.

Methods
A literature review identified relevant information from peer-reviewed publications, congress presentations, and ClinicalTrials.gov. Previously presented but unpublished data from phase 2/3 studies were included.

Results
After 2 MenB-FHbp doses, percentages of adolescents and young adults achieving serum bactericidal activity assay using human complement (hSBA) titers ≥1:8 were 79%–99% for 4 heterologous representative test strains and 71%–97% for 10 additional strains, confirming cross-protection against a diverse strain panel (Figure 1; unpublished data). These 14 heterologous strains collectively represent ~80% of disease-causing strains in the US and Europe. In a published study with limited sample size, 44%–78% of subjects had hSBA titers ≥1:8 against strains from 4 US college outbreaks after 2 MenB-FHbp doses. After 2 MenB-4C doses, percentages of 10–25-year-olds achieving hSBA titers ≥1:5 against 3 reference strains homologous to the vaccine antigen were 82%–93% (published data); 15%–100% of adolescents achieved hSBA titers ≥1:4 against a panel of 14 strains (unpublished data). Of college students who received 2 MenB-4C doses, 53%–93% achieved hSBA titers ≥1:4 against 5 US outbreak strains (4/5 strains had antigenic similarity to MenB-4C; published data).

Conclusion
MenB-FHbp and MenB-4C protect against various serogroup B strains. As for the breadth of coverage provided by these vaccines, available data show that MenB-FHbp elicits robust immune responses to a wide variety of disease-causing strains prevalent in the US (Figure 2).

Disclosures
Tamera Coyne-Beasley, MD, MPH, Pfizer Inc and GlaxoSmithKline (Advisor or Review Panel member) Joseph Bocchini, MD, Pfizer Inc and Dynavax (Advisor or Review Panel member) Alejandro Cane, M.D., Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Maria J. Tort, PhD, Pfizer Inc (Employee, Shareholder) Jessica Presa, MD, Pfizer Inc (Employee, Shareholder)
18. An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Clinical Trials
Authors: Andrew Melissa K , Matthews Sean , Kim Joon Hyung , Riley Megan , Curran Desmond 
Published: December 2021

Abstract

Background
The impact of frailty on the efficacy and safety of vaccines and therapeutic interventions is increasingly recognized, yet assessment of frailty in clinical trials is often considered logistically challenging. We developed the retrospective Clinical Trial Frailty Index (CT-FI), using baseline medical history and patient reported outcomes collected via standard instruments (Short Form Survey-36 and Euro Quality of Life-5 Dimension) in two clinical trials of the adjuvanted recombinant zoster vaccine (RZV, ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]). This post-hoc analysis aimed to show that CT-FI is a robust measure that may be used in any analysis where sufficient patient data has been collected in a clinical trial.

Methods
Items included in the CT-FI were scored from 0 to 1, summed for each participant and divided by the total number of potential deficits. CT-FI was validated using descriptive methods verifying distribution and age- and sex-associations in relation to established FI characteristics, Cox regressions in relation to fatal outcomes hypothetically related to frailty, and re-sampling methods (Jackknife and Bootstrap procedures) within the FI to demonstrate robustness to inclusion/exclusion of specific individual variables.

Results
The CT-FI distribution followed a gamma distribution with a range of 0 to 0.695; the distribution shifted to the right with age. The age-related slope of mean deficit accumulation per year increased with chronological age and was higher for women than men. The rate of mean deficit accumulation was 0.0025 for women vs 0.0016 for men &lt; 70 years of age, and this increased to 0.0058 for women vs 0.0047 for men ≥70 years of age. In univariate and multivariate Cox regression survival analyses, FI, chronological age and sex were significant predictor factors for mortality. The Jackknife and Bootstrap re-sampling methods showed that the performance of CT-FI was not sensitive to inclusion/exclusion of specific individual or groups of variables, demonstrating the robustness of this methodology.

Conclusion
The current analysis validates that CT-FI, an easy-to-implement FI, is a robust method which allows retrospective/prospective evaluation of clinical outcomes by frailty status in clinical trials.

Disclosures
Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Sean Matthews, MSc, GSK (Independent Contractor) Joon Hyung Kim, MD, GSK group of companies (Employee, Shareholder) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder)
29. Impact of Antimicrobial Stewardship Intervention on Unrestricted Meropenem Use Upon Transitions of Care
Authors: Zaidan Noor , Britt Rachel S , Reynoso David , Enwere Emmanuel , Rucker Kathryn , Scott Ferren R 
Published: December 2021

Abstract

Background
Broad-spectrum antimicrobials, like carbapenems, are often initiated empirically and can be continued for long periods of time, which may increase rates of multi-drug resistant organisms. Antimicrobial stewardship programs (ASP) have been shown to decrease the duration of antimicrobial therapy. Since July 2017 at UTMB Health, meropenem use has been restricted to infectious diseases and intensive care unit (ICU) providers. This study evaluated the impact of an electronic medical record (EMR)-based ASP intervention on meropenem days of therapy (DOT) in patients transitioning from the ICU to the general floors.

Methods
Patients aged at least 18 years with an active medication order for meropenem upon transition from an ICU to a medical/surgical unit were included. Once transitioned, the active meropenem order appeared in the “review” column of the pharmacists’ queue. Pharmacists contacted the primary team, requested infectious diseases or ASP approval to continue therapy, and documented communication in the chart. Data for the pre- and post-intervention groups was collected retrospectively for the months of November 2017 to April 2018 and March 2020 to August 2020. The primary outcome of the study was meropenem DOT after transition from the ICU to the medical/surgical unit. Secondary outcomes of the study included meropenem total DOT, total number of meropenem doses after transfer to the medical unit, 30-day all-cause mortality, and 30-day readmission.

Results
A total of 163 patients were evaluated in both the pre-intervention (n = 87) and post-intervention groups (n = 76). Median meropenem DOT after transition of care (3 days vs. 2 days, P = 0.0004) and number of meropenem doses after transition (6 doses vs. 4 doses, P = 0.014) were significantly lower after TOC intervention implementation. However, total meropenem DOTs were not different at 5 days in both groups. Recommendations for de-escalation or discontinuation were accepted 60% of the time among providers.

Conclusion
An EMR-based ASP intervention did decrease meropenem DOT after patients were transitioned from the ICU to the medical/surgical floors. Results of the meropenem EMR-based ASP intervention may be used to expand to other broad-spectrum antimicrobials/antifungals in patients transitioning levels of care.

Disclosures
All Authors: No reported disclosures
32. Impact of a Four-Year Antimicrobial Stewardship Program on Antimicrobial Resistance
Authors: Chrysou Konstantina , Zarkotou Olympia , Mamali Vasiliki , Rekleiti Nektaria , Themeli-Digalaki Katina , Chrysos Georgios , Tsakris Athanasios , Pournaras Spyridon 
Published: December 2021

Abstract

Background
Antimicrobial resistance (AMR) is an increasing threat to public health and antimicrobial consumption is a primary driver of resistance. Many studies have shown that the implementation of an antibiotic stewardship program (ASP) improves prescribing of antibiotics and can reduce AMR. Purpose of the study was to assess the impact of a successful ASP, implemented for four years, on AMR in our 427-bed tertiary general hospital.

Methods
We monitored pharmacy data for the years 2015 (pre-intervention) and 2016-2019 (post-intervention) for antibiotic consumption (DDD/100 bed-days) and resistance rates. AMR data were obtained from the clinical microbiology laboratory’s electronic database. To achieve the goals of ASP we used a range of interventions as pre-authorization strategy for the protected antibiotics (tigecycline, carbapenems, quinolones, glycopeptides, daptomycin, colistin, linezolid), prospective audit and feedback with direct intervention, de-escalation or switch from iv to oral administration and appropriate selection and duration of chemoprophylaxis in surgery.

Results
Significant reductions were observed for: total antibiotics, colistin, carbapenems, quinolones and tigecycline consumption during study period. Significantly lower resistance rates were documented in 2019 compared to 2015 for Pseudomonas aeruginosa and for Klebsiella pneumoniae. As for Acinetobacter baumannii isolates, which in our hospital are highly-resistant exhibiting &gt;90% resistance to carbapenems, no significant changes were noted during the study period. Infections caused by Gram-positive pathogens are less prevalent in our hospital. Lower rates of vancomycin-resistant enterococci were noted after the implementation of our ASP (30.4% in 2019 vs. 50.0% in 2015 for E. faecium and 0.6% vs. 6% for E. faecalis, respectively), whereas methicillin-resistant S. aureus isolates increased (40% in 2019 vs. 31.1% in 2015), possibly because most of these infections were not hospital-acquired.
Resistance rates of Pseudomonas and Klebsiella

Conclusion
Our ASP was successful in reducing antibiotic consumption and AMR for important pathogens.

Disclosures
All Authors: No reported disclosures
48. Local Implementation of an Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria Through Centralized Facilitation Required Minimal Costs and Effort
Authors: Rajan Suja S , Grigoryan Larissa , Van John , Lichtenberger Paola , Patel Payal K , Shukla Bhavarth , Calub Feliza , Brown Nui G , Nguyen Phuong Khanh , Hershey Cheryl , Drekonja Dimitri M , Graber Christopher J , Trautner Barbara 
Published: December 2021

Abstract

Background
The cost of an antibiotic stewardship intervention is an important yet often neglected factor in antibiotic stewardship research. We studied the costs associated with successful implementation of the “Kicking CAUTI” intervention to decrease treatment of asymptomatic bacteriuria (ASB).

Methods
A central coordinating site facilitated roll-out of an audit and feedback intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB in four Veterans Affairs medical centers. Each site had a physician site champion, a part-time research coordinator, and 1-2 additional participants (often pharmacists). Participants kept weekly time-logs to collect the minutes associated with intervention tasks, and percent full-time effort (FTE) and costs were computed. For weeks with missing logs the average minutes for each activity associated with each type of professional was imputed. Salary information was obtained from the Bureau of Labor Statistics and Association of American Medical Colleges.

Results
Research coordinator time comprised of majority of the personnel time, followed by the physician site champions (Figure 1). Each intervention site required about 10% FTE/year of a research coordinator, and 3.5% FTE/year and 3.8% FTE/year of a physician and pharmacist respectively. The coordinating site required 37% FTE/year of a research coordinator, and 9% FTE of a physician to spearhead the intervention. Research coordinators predominantly spent their time on chart-reviews and project coordination. Physician champions predominantly spent their time on delivering audit and feedback and project coordination. The intervention cost USD 22,299/year per site on average, and USD 45,359/year for the coordinating site.

Conclusion
The Kicking CAUTI intervention was successful at reducing urine cultures and associated antibiotic use, with minimal time from the local team members. The research coordinators’ time was primarily spent on collection of research data, which will not be necessary outside of a research project. Our model of centralized facilitation makes economic sense for widespread scale-up and dissemination of antibiotic stewardship interventions in integrated healthcare systems.

Disclosures
Barbara Trautner, MD, PhD, Genentech (Consultant, Scientific Research Study Investigator)
56. High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose Trimethoprim-Sulfamethoxazole: An Opportunity for Antibiotic Stewardship
Authors: Vuong Lisa , Davis Susan L , Davis Susan L , Jedinak Tyler , Medler Corey , Zofchak Kristen , Veve Michael P , Kenney Rachel 
Published: December 2021

Abstract

Background
Trimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX.

Methods
IRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and &gt; 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium &lt; 135 mmol/L, hyperkalemia with potassium &gt; 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed.

Results
Each group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received &gt;1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2.
Table 1. Baseline and Clinical Characteristics

Table 2. Adverse Effects

Conclusion
Patients on IV TMP-SMX therapy were more likely to experience an ADE compared to PO, likely driven by the high volume of free water. Most patients on IV TMP-SMX were on other PO medications, suggesting a missed stewardship opportunity for IV to PO conversion to reduce patient harm.

Disclosures
Susan L. Davis, PharmD, Nothing to disclose Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)
59. Impact of Pharmacist-Led De-Escalation of MRSA Therapy Using MRSA Nasal PCR
Authors: Salvatus Marc , Jung Hemi , Eskandarian Romic , Lee Su 
Published: December 2021

Abstract

Background
Experts suggest that a highly sensitive MRSA nasal PCR can be used to rule out MRSA pneumonia with a negative predictive value greater than 95%. At Adventist Health Glendale (AHGL), the MRSA nasal PCR had a 97% negative predictive value. Pharmacist-led de-escalation of MRSA therapy using MRSA nasal PCR may reduce unnecessary MRSA coverage, patient adverse events, and medication costs. The purpose of this study was to assess the impact on duration of antimicrobial therapy of pharmacist-driven de-escalation of MRSA-targeted antibiotics in pneumonia using MRSA nasal PCR.

Methods
This was a prospective quasi-experimental study (Oct 2018 – Mar 2019 vs. Oct 2019 – Mar 2020) at AHGL, a 515-bed acute care community hospital in Los Angeles, CA, which included adults on MRSA pneumonia agents (either IV vancomycin or IV/PO linezolid). Upon receiving CPOE orders of these MRSA-targeted therapies for pneumonia, the pharmacist ordered a MRSA nasal PCR per protocol for eligible patients, followed up with the results of the MRSA nasal PCR, and recommended to discontinue MRSA therapy if the MRSA nasal PCR was negative. This study received an exemption determination from AHGL IRB.

Results
The total number of patients in the pre-protocol group was 97, and 155 in the post-protocol group. There was a statistically significant decrease in the median duration of MRSA pneumonia agents from the pre-protocol group compared to the post-protocol group (3 days vs. 2 days, P-value = 0.0004). Additionally, there was a statistically significant decrease in the median hospital length of stay from the pre-protocol group compared to the post-protocol group (9 days vs. 7 days, P-value = 0.02).

Conclusion
Implementation of a protocol involving pharmacist-led de-escalation of MRSA-targeted antibiotics for pneumonia utilizing MRSA nasal PCR led to significant decreases in both duration of therapy of MRSA-targeted antibiotics and length of hospital stay.

Disclosures
All Authors: No reported disclosures
70. Impact of the Accelerate Pheno™ System on Clinical and Antimicrobial Outcomes among Inpatients with Gram-Negative Bacteremia at a 528-bed Community Teaching Hospital
Authors: DePasquale William P , Staicu Mary L , Stainton Sean , Laguio-Vila Maryrose R , Hite Mindee , Berg Deanna 
Published: December 2021

Abstract

Background
Traditional methods in blood culture analysis require 24-72 hours to yield identification (ID) and antimicrobial susceptibility testing (AST) results, which may contribute to the use of empiric broad-spectrum antibiotic therapy. Hence, the primary objective of this study was to determine the impact of rapid blood culture analysis with the Accelerate Pheno™ system (AXDX) on time to antibiotic de-escalation.

Methods
This was a single center, case-control analysis of adult inpatients with E. coli or Klebsiella spp. bacteremia. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 after the implementation of AXDX in July 2020. Subjects were matched to historical controls (July 2018-July 2020) based on age (± 3 years), gender, source of infection, and identified organism. The primary outcome was time to antibiotic de-escalation and time to oral antibiotic therapy from the time of positive blood cultures. Secondary outcomes included hospital length of stay, 30-day mortality, 30-day readmission, and 60-day C. difficile infection. Outcomes were compared using descriptive and inferential statistics.

Results
Of 33 cases identified, 30 (91%) were matched with historical controls. E. coli bloodstream infection was identified in 24 (80%) subjects while Klebsiella spp. was identified in 6 (20%) subjects. The average age was 66 years (SD ± 19) and there was an even distribution of males and females in both groups. Other demographics were similar between groups. The median time to species identification [14 hours (IQR 13 – 18) vs 34 hours (29 – 39), p&lt; 0.001) and AST [20 hours (19 – 37) vs 45 hours (38 – 51), p&lt; 0.001] from laboratory registration was significantly shorter in cases. The average time to antibiotic de-escalation was 1.7 (±1.2) days for cases compared to 2 (±1.3) days for controls (p=0.460). Median time to oral antibiotic therapy from positive blood cultures was 2.9 (1.8 – 4.7) days for cases and 3.4 (2.5 – 5.1) days for controls (p=0.166). There were no significant differences in the secondary outcomes.

Conclusion
AXDX did not appear to have a significant impact on time to antibiotic de-escalation and time to oral antibiotic therapy. However, time to organism ID and AST results were significantly shorter in the AXDX cohort.

Disclosures
All Authors: No reported disclosures