bluuebunny/crossref_metadata_2025_split huggingface dataset:
1306. Antimicrobial Resistance Knowledge, Attitudes, and Perceptions Among Medical Students in Southern India
Authors: Menden Olivia , Prabhu Sumathi , Shetty Veena , Pandith Chaithra , Giri Shobha , Shetty Avinash 
Published: November 2018

Abstract

Background
Antimicrobial resistance (AMR) is a major public health problem in India. The World Health Organization recognizes that the education of medical students on antimicrobial stewardship plays a critical role in the efforts to combat AMR, but data related to knowledge, attitudes and practices (KAP) regarding AMR is limited in India.

Methods
This cross-sectional study was conducted in July-August 2017. Medical students at K.S. Hegde Medical Academy in Mangalore, India were surveyed with an anonymous questionnaire using a convenience sampling method involving second year, third year, fourth year, and intern students (n = 347). Data about demographics, sources of information, and antimicrobial training were collected. In addition, AMR knowledge and attitude scores were calculated. A Mann–Whitney U test was used to determine factors that were associated with significant differences in knowledge scores and attitude scores. The primary outcome measure of this study was to determine positive predictors of increased confidence in prescribing antimicrobials in the future using multivariate analysis.

Results
A total of 347 surveys were analyzed (response rate of 98.9%). The mean total knowledge score was 11.47 out to 31 with a standard deviation (SD) of 3.39, and the mean attitude score was 5.99 out of 16 (SD = 4.207). While 13.2% of students were “very familiar” or “familiar” with the term “Antimicrobial Stewardship,” and 88.2% of students said they would like more antimicrobial education in medical school. On multivariate analysis, female gender (OR 2.51, 95% CI (1.51, 4.18)), clinical vignette antimicrobial knowledge scores (OR 1.26, 95% CI (1.05, 1.51)), positive attitude scores (OR 0.94, 95% CI (0.88, 0.995)), awareness of Infection Control Policy (OR 1.87, 95% CI (1.09, 3.22)), and &gt; 3 years of antimicrobial prescribing clinical training (OR 2.48, 95% CI (1.29, 4.75)) were predictors of confidence in antimicrobial prescribing.

Conclusion
This study identifies several possible interventions for improving confidence such as increased clinical knowledge through clinical experience, increased awareness of infection control policies and antimicrobial guidelines, and empowering students to be antimicrobial stewards to combat AMR.

Disclosures
All authors: No reported disclosures.
1310. Improving Infectious Disease Electronic Medical Records Documentation: A Quality Improvement Study in an Academic Teaching Hospital
Authors: Lakshmi Seetha , Asquith Johonna , Alrabaa Sally , Sampson Mindy , Kraitman Natan , Akoghlanian Garabet , Balakrishnan Maya , Casanas Beata 
Published: November 2018

Abstract

Background
Improving efficiency of documentation and sign outs during transitions of care were identified as areas of interest by the University of South Florida Infectious Disease (ID) Division. Our aim is by May 2018, we will achieve &gt;50% improvement in our ID EMR note efficiency score for any adult patient at Tampa General Hospital. Note efficiency score involves listing all of the following key elements with 1 point awarded for each: active problem in the subjective section, updated hospital course under assessment, active problem prioritized first under assessment and non-relevant problems removed from assessment.

Methods
Institute of Healthcare Improvement’s model with Plan-Do-Study-Act (PDSA) cycles was used for project implementation from March 2018 to May 2018 (Figure 1). Cycle 1: Conducting a needs assessment survey and education. Cycle 2: Changing the existing template and implementing a new standardized template that includes the key elements, along with removal of auto populated non relevant information. Audits of notes with a 4-point system scoring was done. A pre and post implementation physician survey was conducted.

Results
ID fellow and faculty completed the baseline survey (N = 25). Less than half (46%) felt that they could interpret patient assessments with ease and even fewer respondents (36%) felt there was adequate weekend sign out. More than one-third (36%) reported writing majority of notes after 5 pm (Figure 1). Pilot project involved nine ID faculty and fellows. We had 95% compliance with use of the standardized EMR template. Notes were evaluated at baseline (n = 190), cycle 1 (n = 85), and cycle 2 (n = 56). An increase in average note efficiency score from baseline, cycle 1 and cycle 2 occurred as follows (Mean ± SD): 2.0 ± 0.84 vs. 2.8 ± 0.95 vs. 3.6 ± 0.5 (Figure 2). Compared with baseline, cycle 2 achieved 42% improvement in the ease of interpretation of patient assessments and 41% improvement in adequate sign out. No increase in note writing after 5pm (36% vs. 30% baseline and cycle 2, respectively) reported.

Conclusion
Targeted education and changing the EMR note template can achieve improved efficiency of ID note. These efforts to improve documentation enhance physician’s ease of interpretation of patient assessments and sign out during transition of care.

Disclosures
All authors: No reported disclosures.
1313. Does Time Fly When Having Fun? A Study Assessing the Relationship Between Estimated Time on Task and Enjoyment of Infectious Diseases Serious Games
Authors: Jeffres Meghan , Biehle Lauren R 
Published: November 2018

Abstract

Background
Mastering the fundamentals of infectious diseases (ID) requires students to memorize large volumes of material about pathogens, antibiotics, patients, and the interactions between the three. It is hypothesized that there is a positive relationship between time on task and engagement. The objective of this study was to explore the relationship between enjoyment of a serious game and the estimated time spent playing.

Methods
During a one-time session, students from two colleges of pharmacy engaged in three ID game-based active learning strategies each lasting a pre-specified time. These strategies included a card game about calculations (Fightin Figures, FF), a quiz game about antibiotic fundamentals (Rapid Rounds, RR), and a board game using NAPLEX practice examination questions (Pills and Placebos, PP). Students completed a survey for each game assessing enjoyment and estimated time spent playing each game.

Results
Eighty-four students participated. Demographics of the sample include female 53%, mean age 26.7 years, and mean GPA 3.6. Using a Likert scale from 1–10 (1 = not enjoyable, 10 = very enjoyable) student rated each game: FF 6.5 ± 2.2, RR 7.2 ± 2.3, PP 8.4 ± 1.8. The time estimation ratio, calculated by dividing the estimated time by the actual time for each game was 0.9 ± 0.5 for FF, 1.5 ± 0.6 for RR, and 1.0 ± 04 for PP. The percentage of students who underestimated time spent playing was 57% for FF, 8% for RR, and 41% for PP. There were no differences in time estimation ratio based on sex, age, or GPA.

Conclusion
Although a small study, there was no trend toward association of time underestimation and enjoyment of these teaching methods. Students enjoyed the board game PP the most yet the time estimation ratio was 1.0, indicating estimated and actual time on task were the same. Students enjoyed FF the least but this was the only game they underestimated time spent on task.

Disclosures
All authors: No reported disclosures.
1326. Inter-Professional Education and Training to Build Capacity Among Healthcare Workers in Singapore
Authors: Michaels Jessica , Olszyna Dariusz , Ng Frank , Lee Cheng Chuan , Archuleta Sophia 
Published: November 2018

Abstract

Background
People Living with HIV (PLHIV) in Singapore continue to face stigma and confidentiality concerns in their interactions with Healthcare Workers (HCWs). There is a recognized gap in HIV-related knowledge and lack of training opportunities for HCWs in Singapore, particularly amongst nonphysicians and other HCWs who do not regularly care for PLHIV. The HCW HIV Education Series was conceptualized to address these issues and to improve the HIV-related knowledge, attitudes and practices of HCWs in Singapore.

Methods
The HCW HIV Education Series is organized by an interprofessional organizing committee. The series is made up of four half day modules which are conducted quarterly. The modules are designed and implemented to cater to as many HCWs as possible. The modules function as a series but can also be run as standalone education sessions. The modules are: HIV Basics, Working with PLHIV, Basic HIV Clinical Care and Advanced HIV Clinical Care. In its pilot year (2016–2017), 334 HCWs, predominantly nurses, pharmacists, and social workers attended the series. The HCWs attended from diverse healthcare settings, including public and private hospitals, nursing homes, faith based and community organizations. Pre- and post-module evaluations were completed by participants.

Results
Only 5% of Module 1 attendees had previously received training in HIV. Across all four modules, there was a marked improvement in knowledge and confidence pre- and post-training. 95% of attendees across all modules felt that they had gained new skills that would add value to their work. While 97% of attendees of Module 1 planned to attend future modules, the attrition rate between modules was high.

Conclusion
The HCW HIV Education Series is highly evaluated and well attended. Efforts to maintain and strengthen attendance across all modules is needed, the delivery of the modules over a 2-day period may be an effective way to achieve this. Research into the experiences of PLHIV in healthcare facilities should also be considered.

Disclosures
All authors: No reported disclosures.
1354. Novel Formulation SUBA-Itraconazole in Fed and Fasted Healthy Volunteers: Expanding the Clinical Utility of the Established Mold Active Agent
Authors: Lindsay Julian , Mudge Stuart 
Published: November 2018

Abstract

Background
Itraconazole has been established as an effective mold active agent; however, wide interpatient variability in bioavailability and poor gastrointestinal tolerability have made using the agent challenging. A novel formulation, SUBA-Itraconazole (SUperBioAvailable) has been developed by Mayne Pharma to alleviate these negative properties.

Methods
An open-label, randomized, cross-over study of SUBA–Itraconazole capsules 65 mg (2 × 65 mg BID) in healthy adults under fasting and fed conditions was assessed for steady-state levels. Subjects (n = 20) were administered two capsules of SUBA–Itraconazole twice daily on Days 1–14 and once on the morning of Day 15, either on an empty stomach or with a meal. Safety was monitored by vital signs measurements, electrocardiogram measurements, clinical safety laboratory tests (liver and kidney function tests), and physical examination.

Results
Overall, SUBA–Itraconazole demonstrated similar concentrations at the end of the dosing interval (trough), with modestly lower total and peak exposure when administered under fed conditions compared with the fasted state (fed/fasted ratios of 78.09% for AUCtau [14,183.2 vs. 18,479.8] 73.05% for Cmax,ss [1,519.1 vs. 2,085.2] and 91.53% for Ctrough[1,071.5 vs. 1,218.5]); see Figures 1 and 2. The administration of SUBA–Itraconazole 65 mg capsules was well-tolerated by the healthy subjects participating in this study.

Conclusion
The results demonstrate a promising clinical utility for SUBA–Itraconazole in practice. Unlike the conventional capsule formulation which requires a high fat meal for absorption, or the oral solution formulation which requires a fasted administration, SUBA–Itraconazole reached a therapeutic steady state in both fasted and fed states. The similar trough level, however higher peak with fasted state, likely represents a more gradual absorption of drug in the fed state. The slightly higher bioavailability in a fasted state, without gastrointestinal intolerability, is particularly promising for the clinical use of SUBA–Itraconazole in patients unable to have a high fat content meal due to chemotherapy or post-surgery such as hematology patients and transplant recipients.

Disclosures
J. Lindsay, Mayne Pharma: Consultant, Consulting fee. S. Mudge, Mayne Pharma: Employee, Salary.
1361. Pharmacokinetics and Safety of Ridinilazole (RDZ), a Potential New Therapy for Clostridium difficile Infection (CDI): From Animal Models to Patients
Authors: Duperchy Esther , Chowdhury Sumita , Vickers Richard , Robinson Neil 
Published: November 2018

Abstract

Background
CDI is the leading cause of nosocomial diarrhea associated with 29,000 deaths p.a. in the United States. RDZ is a novel oral drug highly selective for C. difficile limiting collateral damage to the gut microbiota. Here we present a combined analysis of all pharmacokinetic (PK) and tolerability data obtained throughout the development of RDZ from animal models to Phase 2, including new human PK data.

Methods
RDZ levels were measured in plasma and in the GI tract of infected hamster after a single oral dose at 25 mg/kg. Quantitative whole-body autoradiography (QWBA) and excretion mass balance studies were performed in rats following a single 50 mg/kg oral dose of 14C RDZ. In GLP toxicology studies, RDZ was administered orally for 28 days to dogs and rats at 1,000 mg/kg/day. Toxicokinetic, clinical pathology, and histopathology analysis were performed. The Phase 1 study enrolled 56 healthy male subjects receiving single ascending doses from 2 to 2,000 mg, or, 200 or 500 mg BID for 10 days. The Phase 2 enrolled 100 patients assigned 1:1 to 10 days oral RDZ 200 mg BID or VAN 125 mg QID treatment. Both clinical trials quantified RDZ in plasma and feces, and assessed safety and tolerability.

Results
In all animal studies, plasma levels of RDZ were below or at the limit of quantification (LOQ, 1.0 ng/mL). In the GI tract of hamsters, RDZ levels were highest in the colon. QWBA and excretion studies showed RDZ accumulated in the cecum and colon, the site of infection; &gt;99% of radioactivity was excreted in feces and no radioactivity was detected systemically. 28 days repeat dosing in dog and rat resulted in no observations from treatment, histopathology or in-life parameters. In Phase 1 and 2 studies, RDZ plasma levels were generally near or below the LOQ (0.1 ng/mL). Concomitant medications, CDI severity, and age had no impact on exposure. In Phase 1, AEs were mild with no dose-dependent relationship, occurring and at a similar incidence to placebo. No significant findings from clinical laboratory, ECGs or other assessment were observed. RDZ was well tolerated in Phase 2 with the incidence of AEs and SAEs similar in both RDZ and VAN groups.

Conclusion
In both clinical and nonclinical studies to date, RDZ has been well tolerated and associated with low systemic absorption. Further assessment of safety, tolerability, and PK in Phase 3 studies is warranted.

Disclosures
E. Duperchy, Summit Therapeutics: Employee, Salary. S. Chowdhury, Summit Therapeutics Inc.: Employee and Shareholder, Salary and Shareholder. R. Vickers, Summit Therapeutics: Employee, Salary and Stock options. N. Robinson, Summit Therapeutics: Consultant, Consulting fee.
1367. Clinical Cure in Secondary Efficacy Populations in Patients With Complicated Urinary Tract Infection Treated With ZTI-01 (Fosfomycin for Injection): Findings From the ZEUS Trial
Authors: Kaye Keith , Rice Louis B , Stus Viktor , Sagan Olexsiy , Fedosiuk Elena , Das Anita , Skarinksy David , Eckburg Paul B , Manvelian Kristina , Ellis-Grosse Evelyn J 
Published: November 2018

Abstract

Background
ZTI-01 (fosfomycin for injection) is an investigational epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has a broad spectrum of in vitro activity, including multidrug-resistant Gram-negative pathogens, and is being developed for the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.

Methods
ZEUS was a multicenter, double-blind, Phase 2/3 trial in hospitalized adults with cUTI and AP to evaluate safety and efficacy. Randomized patients received 6 g ZTI-01 q8h or 4.5 g IV piperacillin/tazobactam (PIP-TAZ) q8h for 7 days; patients with baseline bacteremia could receive up to 14 days; study continued to late follow-up (LFU, 26 ± 2 days). Oral step-down therapy was prohibited. ZTI-01 met the primary endpoint of noninferiority to PIP-TAZ. Secondary objectives included comparing clinical cure rates (assessed by investigator) in the modified intent-to-treat (MITT), microbiologic MITT (m-MITT), clinical evaluable (CE), and microbiologic evaluable (ME) populations at test-of-cure (TOC, Day 19 ± 2 days).

Results
There were 464 patients randomized who received study drug. In all populations, clinical cure rates at TOC were high and similar between treatment groups (&gt;90%) (table).

Conclusion
These results demonstrate consistent efficacy in multiple secondary efficacy populations for patients with cUTI and AP who were treated with either ZTI-01 or PIP-TAZ. If approved by FDA, ZTI-01 may provide a new IV option with a differentiated MOA for patients in the United States with serious Gram-negative infections.
95% confidence intervals (CIs, two-sided) were computed using a continuity-corrected Zstatistic.

Disclosures
K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. V. Stus, Zavante Therapeutics, Inc.: Investigator, Research support. O. Sagan, Zavante Therapeutics, Inc.: Investigator, Research support. E. Fedosiuk, Zavante Therapeutics, Inc.: Investigator, Research support. A. Das, Zavante Therapeutics, Inc.: Consultant, Consulting fee. D. Skarinksy, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder, Consulting fee. K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary.
1382. Acute Kidney Injury with Piperacillin–tazobactam and Vancomycin in the Intensive Care Unit
Authors: Smith Tameka , Lewis James S , Forrest Graeme N 
Published: November 2018

Abstract

Background
Several recent retrospective studies have suggested that the combination of vancomycin (V) with piperacillin–tazobactam (PTZ) is associated with increased nephrotoxicity. We prospectively evaluated the outcomes of patients admitted to all of our medical and surgical intensive care units (ICU) with a normal baseline creatinine clearance (CrCl) that received vancomycin in combination with either cefepime (CEF) or PTZ to determine whether kidney injury occurs using RIFLE criteria.

Methods
ICU patients who received combinations of V with either PTZ or CEF were prospectively evaluated from June 1, 2017 to April 28, 2018 using Theradoc. V and PTZ dosing were standardized per ICU policy and monitored by clinical pharmacists. We included patients between ages 18 and 90, and receipt of &gt;72 hours of combination antibiotic therapy. We excluded patients that were pregnant, had a hematologic malignancy, chronic kidney disease, or neuromuscular disease. Data collected included, CrCl, V troughs, dosage and length of all antibiotics used, ICU length of stay (LOS), and co-administered nephrotoxic medications (e.g., NSAIDs and IV contrast). The primary objective was to compare the incidence of AKI in these study groups, as defined by the RIFLE criteria.

Results
Of 233 patients evaluated, 58 (25%) met inclusion criteria, 45 received PTZ-V and 13 CEF-V. Only eight of 58 (14%) MRSA-positive culture.
We found no correlation with co-administered nephrotoxic agents, vancomycin troughs, or body weight and AKI.

Conclusion
Our prospective observational study data revealed significant AKI with PTZ-V compared with CEF-V but it did not impact patient long-term outcomes. Caution with PTZ-V may be required when used in ICU settings even in patients with normal baseline CrCl.

Disclosures
J. S. Lewis II, Merck: Consultant, Consulting fee.
1384. RSV Monoclonal Antibody (MK-1654) Phase 1 Pharmacokinetics (PK) in Healthy Adults and Population PK Modeling to Support Pediatric Development
Authors: Maas Brian , Aliprantis Antonios , Wolford Dennis , Fayad Ghassan , Vora Kalpit , Geng Dong , Ma Hua , Caro Luzelena 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection and hospitalization in infants. MK-1654 is a monoclonal antibody (mAb) being developed to prevent RSV infection in infants and is undergoing evaluation in a Phase 1 study. Incorporation of YTE mutations extend its half-life to allow for dosing once every RSV season. Preliminary Phase 1 PK results and the development of a population PK model that characterizes adult PK to predict pediatric exposures are presented here.

Methods
In this double-blinded Phase 1 study, 152 healthy males and females of nonchildbearing potential aged 19–59 years were randomized in a 3:1 ratio to receive a single dose of MK-1654 or placebo as a bolus intramuscular injection (IM) or in an intravenous infusion (IV) over 2.5 hours. Dose levels included 100 mg IM, 300 mg IM, 300 mg IV, 1,000 mg IV and 3,000 mg IV. Serial serum samples were collected to measure MK-1654 PK via a validated LC/MS assay. A noncompartmental PK analysis was conducted using preliminary data from 60 subjects up to Day 150 (900 observations). A population PK model was developed to simultaneously characterize the IM and IV adult PK data and to predict pediatric PK through allometric scaling. Pediatric MK-1654 PK was predicted for several IM doses for a typical sized infant (35 weeks gestational age at birth; 4 months chronological age at dosing; 50th percentile weight).

Results
In adults, the median time to maximum concentration observed was ~6–10 days following IM injection. The apparent half-life of MK-1654 ranged from ~70–85 days after either IM or IV doses. The estimated IM bioavailability was ~71%. Cmax and AUC0-90 days increased dose proportionally following IV administration. MK-1654 adult PK was best characterized using a two-compartment model with first-order elimination. IM absorption was described using a first-order rate constant with lag time. Inter-individual variability was included for clearance (CL and Q), central volume (V2), and absorption rate (Ka). The pediatric model suggested apparent terminal half-life in a typical infant is shorter than adults, likely being driven by infant growth during treatment.

Conclusion
Predicted infant PK profiles support further development of MK-1654 in children.

Disclosures
B. Maas, Merck: Employee and Shareholder, Salary and stock options. A. Aliprantis, Merck: Employee and Shareholder, Salary and stock options. D. Wolford, Merck: Employee and Shareholder, Salary and stock options. G. Fayad, Merck: Employee and Shareholder, Salary and stock options. K. Vora, Merck: Employee, Salary. D. Geng, Merck: Employee and Shareholder, Salary and stock options. H. Ma, Merck: Employee and Shareholder, Salary and stock options. L. Caro, Merck: Employee and Shareholder, Salary and stock options.