bluuebunny/crossref_metadata_2025_split huggingface dataset:
1312. Division Divided: Using Debate as an Educational Tool to Teach Evidence-Based Clinical Decision-Making
Authors: Spicer Jennifer O , Phadke Varun K 
Published: November 2018

Abstract

Background
In medical education, there has been a push to implement innovative teaching techniques that encourage critical thinking rather than just knowledge dissemination. Debate promotes critical thinking by challenging individuals to consider alternate viewpoints, which could make it an ideal format to review the evidence relevant to common clinical dilemmas in infectious diseases (ID). We describe a pilot of one such debate format in our ID fellowship program.

Methods
We reviewed literature regarding the effectiveness of ceftriaxone for outpatient antibiotic therapy (OPAT) in methicillin-susceptible Staphylococcus aureus (MSSA) osteoarticular infections. The evidence was presented as a structured debate in place of our weekly case conference. Pre- and post-session surveys containing multiple choice questions and Likert items were administered to assess the impact of the debate on attendees’ knowledge, attitudes, and practices on this topic along with their attitudes toward the debate format. Differences between pre- and post-session surveys were analyzed using paired t-tests and McNemar’s test.

Results
At the first debate 33 residents, fellows, and faculty members were present, and 24 (73%) completed both the pre- and post-session surveys. Attendees demonstrated significant improvement between the pre- and post-session knowledge questions, which covered the following topics: study design of articles supporting ceftriaxone use (31% vs. 62%, P = 0.008), appropriate method to assess ceftriaxone susceptibility (64% vs. 100%, P = 0.004), and whether the inoculum effect applies to ceftriaxone (35% vs. 77%, P = 0.003). After the debate, attendees were more willing to use ceftriaxone (P = 0.001) and felt more familiar with the literature (P &lt; 0.001). The post-session survey showed that individuals both enjoyed the format and found it effective (Figure 1). Most individuals stated that they were either extremely likely (85%) or likely (8%) to attend if this format was used again. Written comments included “strongly recommend continuing this format” and “much better than regular case conference with more discussion and critical thinking.”

Conclusion
Debate appears to be an effective and enjoyable format to teach clinical controversies in ID.

Disclosures
All authors: No reported disclosures.
1318. Are We PrEPared? Awareness and Prescribing Patterns of HIV Pre-Exposure Prophylaxis (PrEP) by Internal Medicine Resident Physicians at an Academic Medical Center
Authors: Hornak J Patrik 
Published: November 2018

Abstract

Background
HIV PrEP uptake remains low by primary care physicians, amongst whom increased awareness has been positively associated with its adoption. Prior studies have also revealed deficits in knowledge and comfort providing PrEP amongst internal medicine (IM) trainees. This is among the first reports of assessing PrEP uptake by IM residents; this appears to be the first examining pre- and post-instruction assessment of prescribing attitudes following a single lecture on the topic.

Methods
An anonymous, online survey was distributed to all IM residents at our institution to measure baseline PrEP awareness and prescribing patterns. A comprehensive PrEP lecture was formulated with assistance from infectious diseases (ID) faculty; focus was paid to addressing concerns about cost, safety, risk behavior compensation, and drug resistance. The lecture was made available electronically to those unable to attend the live session. PrEP knowledge and prescribing attitudes were measured and compared pre- and post-lecture. Fisher’s exact test was used for descriptive statistics.

Results
Of 97 initial surveys distributed, 41 were completed. A majority of respondents were aware of PrEP (68%). A modest number had either prescribed PrEP or referred a prospective patient to an ID specialist in the prior year (15%). The majority preferred to learn about PrEP with a dedicated didactic session (76%). Compared with baseline data, following the lecture, residents were better able to identify both the number of daily pills required (100% vs. 49%, P = 0.007) and the proper medication regimen (100% vs. 49%, P = 0.007); there was no significant difference in self-reported comfort with providing PrEP (89 vs. 65%, P = 0.25). In the post-lecture survey, nearly half reported a preference to refer a PrEP candidate to an ID specialist or PrEP clinic (43%).

Conclusion
These findings suggest value in providing PrEP education to IM trainees, but indicate that a single lecture may not be effective for ultimately improving its adoption by this important group of physicians. Determining the optimal method for incorporating PrEP into residency curricula deserves further study. Despite efforts to expand PrEP into the realm of primary care, many of these physicians may continue to defer management of these patients to ID/HIV clinicians.

Disclosures
All authors: No reported disclosures.
1321. The UNZA/UMB MMed ID Collaboration: Training and Retaining HIV Specialist Physicians in Zambia
Authors: Hachaambwa Lottie , Claassen Cassidy , Mulenga Lloyd , Lambwe Nason , Sikazwe Izukanji , Watson Douglas , Patel Devang , Bositis Christopher , Sheneberger Robert 
Published: November 2018

Abstract

Background
To mitigate the HIV pandemic and increasing outbreaks of infectious diseases, sub-Saharan African countries need increased healthcare worker capacity at all levels. We describe a successful collaboration between the Ministry of Health (MOH), the University Teaching Hospital (UTH), the University of Zambia (UNZA), and the University of Maryland Baltimore (UMB) to train Zambian physicians in advanced HIV medicine and infectious diseases.

Methods
Recognizing the need for advanced HIV clinical care expertise in Zambia, UNZA, UTH and UMB partnered in 2008 to create a 1-year Postgraduate Diploma in HIV Medicine. The consortium extended this to an 18-month Master of Science in HIV Medicine to better align with existing professional advancement schema. In 2012, UNZA and UMB started a 4-year Master of Medicine in infectious diseases (MMedID), which was then expanded to a 5-year training program combining internal medicine and infectious disease (MMed IM/ID) in order to produce a cadre with wider expertise in internal medicine and infectious diseases. Instruction consists of bedside teaching, didactic lectures, case conferences, and journal clubs. The bulk of teaching came from UMB clinical faculty with expertise in HIV and ID; faculty are either based in Zambia or visit from the United States.

Results
The MSc HIV program trained 27 physicians; of these, 24 (89%) are in health leadership positions in Zambia, with 17 (63%) directly involved in clinical care (mostly in the public sector), while 7 (15%) work for international implementing partners in Zambia. 1 physician emigrated to another African country, another one died and the third is in clinical nonleadership position in Zambia. The MMed ID program has enrolled 14 physicians. The first two graduates of the program completed the program in 2017 and took health leadership roles within the MOH as well as teaching positions at UNZA.

Conclusion
Educational collaborations embedded within local institutions and structures can provide advanced healthcare expertise within resource-limited settings. The UNZA/UMB MMed IM/ID collaboration is a model example of a successful university partnership that has resulted in retaining health leadership and clinical care expertise in Zambia.

Disclosures
L. Hachaambwa, Centers for Disease Control and Prevention (CDC): Cooperative Agreement to Institution, Financial support for the work described in this abstract was made possible by a cooperative agreement award from the Centers for Disease Control and Prevention (CDC) to the University of Zambia and to the University of Maryland School of Medicine.
1327. Educational Intervention to Improve Communication With Patients Who Have Opioid Use Disorder
Authors: Kershaw Colleen , Stead Wendy , Rowley Christopher F 
Published: November 2018

Abstract

Background
Infectious complications of opioid use disorder (OUD) have increased significantly in the last decade. Patients with OUD encounter stigma from healthcare providers, and providers find interactions with patients with OUD to be very challenging. At our teaching institution, anecdotal experience and objective data suggested clinician discomfort with communicating with OUD patients, as well as a “hidden curriculum” of stigma and bias around care of this group. We attempted to characterize this problematic learning environment and created an intervention focusing on reduction of bias and stigma and improved communication with OUD patients.

Methods
General internal medicine faculty and residents completed a preintervention survey to measure knowledge and attitudes about OUD, as well the institutional learning environment related to this issue. A workshop on communication, bias, and stigma in OUD was then administered to 78 faculty and residents. Immediately after participation, they completed a postintervention survey assessing concepts addressed in the session.

Results
The preintervention survey of 99 faculty and residents showed that 47% felt patients with OUD were difficult to work with. Faculty were more likely than residents to agree there was a negative hidden curriculum around OUD (70% vs. 43%, P &lt; 0.001). This included witnessing other physicians using stigmatizing language (80%), minimizing time with OUD patients (49%), and choosing not to involve medical students with OUD patients (34%). Fifty participants completed the postsurvey. Respondents identified a mean of 86% of stigmatizing words within patient scenarios, which improved from 60% before the intervention (P &lt; 0.0001).

Conclusion
Clinicians reported negative attitudes and difficulty caring for patients with OUD. The majority identified a negative hidden curriculum around this disease, including stigmatizing language and avoidance of engagement with OUD patients. A workshop on communication, stigma, and bias improved scores on knowledge of stigmatizing language.

Disclosures
All authors: No reported disclosures.
1335. Safety and Pharmacokinetic Profile of PC786, a Novel Inhibitor of Respiratory Syncytial Virus L-protein Polymerase, in a Single and Multiple-Ascending Dose Study in Healthy Volunteer and Mild Asthmatics
Authors: Cass Lindsey , Davis Amanda , Murray Alison , Woodward Kathy , Ito Kazuhiro , Strong Pete , Rapeport Garth 
Published: November 2018

Abstract

Background
RSV is the most common cause of bronchiolitis in infants and is responsible for severe respiratory infections in the elderly and immunocompromised populations. RSV replicates in the columnar epithelial cells of the proximal and distal airways which are accessible to inhaled therapies. PC786 is a potent non-nucleoside RSV L-protein polymerase inhibitor designed for inhaled delivery. In preclinical studies, PC786 exhibits prolonged lung tissue residence with minimal systemic exposure, thus limiting the potential for adverse systemic effects.

Methods
A phase 1 study was conducted to evaluate the safety and pharmacokinetics of PC786 delivered in a suspension formulation by nebulizer (PARI LC SPRINT® device). Healthy volunteers (HVs) received placebo or PC786 as single ascending doses (0.5–20 mg, Cohort (C) 1), 5 mg BD for 7 days (C2), or 10 mg BD for 7 days (C3). Mild asthmatics received a single dose of PC786 5 mg or placebo (C4). PC786 PK was measured in plasma and in nasal mucosal lining fluid (MLF) collected using a synthetic absorptive matrix.

Results
PC786 was well tolerated, with no significant adverse clinical nor laboratory findings. Following single inhaled doses PC786 appeared rapidly in the plasma; mean plasma Cmax of 190, 571, 1,760, and 3,270 pg/mL, for the 0.5, 2, 8, and 20 mg doses, respectively, were measured on average at 0.68 to 0.93 hours (Tmax) post-inhalation. Following administration of 5 mg BD (C2) the extent of accumulation was approximately 2-fold. The geometric mean apparent terminal half-life measured following 10 mg BD (C3) was 97 hours. The ratio of MLF:plasma concentrations ranged from 6,347 (+2 hours) to 1,050 (+24h).

Conclusion
PC786 was well tolerated by HVs and asthmatics. The compound showed a rapid Tmax, suggesting rapid exposure of the respiratory epithelium. The PC786 concentrations in MLF exceed the IC90 for RSV, but circulating plasma concentrations were low. The MLF:plasma measured in this study was consistent with lung:plasma ratios measured in preclinical studies. The long plasma half-life is consistent with slow absorption from the lung being the dominant process controlling systemic kinetic behavior. The long t½ and 2-fold accumulation ratio observed on repeat dosing supports once daily dosing in subsequent studies.

Disclosures
L. Cass, Pulmocide Ltd.: Employee and Shareholder, Salary. A. Davis, Pulmocide Ltd.: Employee and Shareholder, Salary. A. Murray, Pulmocide Ltd.: Employee and Shareholder, Salary. K. Woodward, Pulmocide Ltd.: Consultant, Consulting fee. K. Ito, Pulmocide Ltd.: Employee and Shareholder, Salary. P. Strong, Pulmocide Ltd.: Board Member, Employee and Shareholder, Salary. G. Rapeport, Pulmocide Ltd.: Board Member, Employee and Shareholder, Salary.
1336. Assessment of the In Vivo Efficacy of WCK 5222 (Cefepime-Zidebactam) Against Carbapenems-Resistant Acinetobacter baumannii (CR-ACBN) in the Neutropenic Murine Thigh Infection Model
Authors: Abuhussain Safa Almarzoky , Avery Lindsay , Abdelraouf Kamilia , Nicolau David P 
Published: November 2018

Abstract

Background
Zidebactam (ZID) is a novel β-lactam enhancer with high binding affinity to PBP2 and intrinsic activity against many Gram-negative pathogens, with the exception of ACBN. ZID also inhibits β-lactamases but not OXA carbapenemases associated with ACBN or metallo-β-lactamases. However, WCK 5222 (a combination of cefepime [FEP] and ZID) has shown in vitro activity against ACBN, including OXA producers. Moreover, we have previously shown that WCK 5222 human-simulated regimen (HSR) causes extensive (i.e., &gt;2 log) eradication of ACBN from neutropenic mice lung. This study aimed to evaluate the in vivo efficacy of the HSR of WCK 5222 compared with FEP HSR or ZID HSR alone against ACBN in the neutropenic murine thigh infection model.

Methods
Six CR-ACBN clinical isolates, including five isolates expressing OXA-23 or OXA-24, were studied. FEP and WCK 5222 MICs were 128 to &gt;512 and 16 to 64 mg/L, respectively. The ZID MIC was &gt;512 mg/L for all isolates. ICR mice were rendered transiently neutropenic via cyclophosphamide prior to thigh inoculation with bacterial suspensions of 107 CFU/mL. Treatment mice received either FEP HSR (equivalent to a clinical dose of 2 g IV q8h as a 1 hour infusion), ZID HSR (equivalent to a clinical dose of 1 g IV q8h as 1 hour infusion), or WCK 5222 HSR (FEP HSR + ZID HSR). Control mice were vehicle-dosed. Changes in log10 CFU/mL at 24 hours compared with 0 hours controls were measured to assess efficacy.

Results
The average log10 CFU/thigh at 0 hours across all isolates was 5.85 ± 0.22. Compared with 0 hours control, the mean bacterial growth at 24 hours in the untreated control mice, FEP HSR, and ZID HSR were 2.34 ± 0.93, 1.36 ± 1.40, and 2.04 ± 0.80 log10CFU/thigh, respectively. The WCK 5222 HSR produced a decline in bacterial burden for all isolates [mean reduction of −2.09 ± 1.01 log10CFU/thigh]; 4/6 isolates achieved ≥ 2-log reduction while ≥1-log reduction was attained with the remaining two isolates.

Conclusion
HSR of WCK 5222 showed potent in vivo activity against CR-ACBN expressing OXA carbapenemases in the murine thigh model which is attributed to the β-lactam enhancing effect of ZID, driven by the complementary PBP binding of FEP and ZID. These results support the clinical evaluation of WCK 5222 for the management of infections due to CR-ACBN.

Disclosures
D. P. Nicolau, Wockhardt: Investigator, Research support.
1342. Comparison of Lysin CF-301 (Exebacase) Activity Against S. aureus Isolates From Bacteremic Patients Enrolled in a Phase 2 Study (CF-301-102) to Contemporary Surveillance Isolates
Authors: Anastasiou Diane , Jandourek Alena , Traczewski Maria , Cassino Cara , Schuch Raymond 
Published: November 2018

Abstract

Background
CF-301 (exebacase) is a novel, recombinantly produced, bacteriophage-derived lysin (cell wall hydrolase) which is the first lysin to enter Phase 2 (Ph2) in the United States and is being studied for the treatment of S. aureus bacteremia including endocarditis. We examined the activity of CF-301 against methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) isolates from participants in the ongoing, CF-301 “first in-patient’ Ph2 study (NCT03163446) in comparison to activity reported in a recent surveillance study.

Methods
Patients with complicated bacteremia or endocarditis caused by S. aureus were enrolled into Study CF-301-102 at study centers in the United States and Guatemala between 2017 and 2018. Baseline isolates from blood cultures were collected prior to administration of CF-301. The activity of CF-301 activity against the first 36 isolates of MRSA (14) and MSSA (22) was determined at a central laboratory. Surveillance data for CF-301 were generated against 300 isolates of MRSA (150) and MSSA (150) collected between 2016 and 2017 from patients with various infection types at US centers. CF-301 MICs were determined using the modified broth microdilution method approved by the CLSI for CF-301.

Results
In vitro activity of CF-301 against S. aureus isolates from Ph2 Study CF-301-102 and surveillance

Conclusion
The activity of CF-301 against baseline S. aureus isolates from blood cultures obtained from bacteremic patients enrolled in the Ph2 study was similar to that observed in the surveillance study. Based on data from previously presented exposure target attainment animal studies, PK/PD modeling and preliminary non-clinical breakpoint assessments, we expect that strains with MIC values of ≤1 µg/mL will be susceptible to the clinical CF-301 dose (0.25mg/kg) under study in Ph2.

Disclosures
D. Anastasiou, ContraFect Corporation: Consultant, Consulting fee. A. Jandourek, ContraFect Corporation: Employee, Salary. C. Cassino, ContraFect Corporation: Employee, Salary. R. Schuch, ContraFect Corporation: Employee, Salary.
1343. Prophylactic Dosing of Baloxavir Acid Eliminates Mortality in Mice Lethal Influenza A Virus Infection Model
Authors: Shano Shinya , Fukao Keita , Noshi Takeshi , Sato Kenji , Sakuramoto Masashi , Baba Kaoru , Shishido Takao , Naito Akira 
Published: November 2018

Abstract

Background
Baloxavir acid (BXA), an active form of orally available prodrug baloxavir marboxil (BXM, formerly S-033188), is a novel small molecule inhibitor of cap-dependent endonuclease (CEN) of influenza A and B virus, and was recently launched for the treatment of acute and uncomplicated influenza with single dosing of BXM (the trade name XOFLUZA™) in Japan in March 2018. Here, we evaluated the prophylactic efficacy of BXA in mice lethally infected with influenza A virus.

Methods
T1/2 of BXA in human is more than 10 times longer than that in mice. Therefore, suspension of BXA was subcutaneously administered at 0.8 or 1.6 mg/kg in mice to maintain the plasma concentration of BXA as seen in humans, and then mice were intranasally inoculated with a lethal dose of A/PR/8/34 strain at 48, 72, or 96 hours after the administration of BXA. Survival time and body weight change were then monitored through a 28-day period after virus infection. Mice were euthanized and regarded as dead if their body weights were lower than 70% of the initial body weights according to humane endpoints.

Results
Single dosing of BXA (1.6 mg/kg) completely eliminated mortality in mice, when the mice were administrated the drug at 48, 72, or 96 hours before virus infection (Figure 1). BXA treatment also significantly prevented body weight loss, consistent with the prolonged survival.

Conclusion
Prophylactic dosing of BXA exhibited significant protective efficacy against mortality and body weight loss in mice following a lethal infection with influenza A virus. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of BXM for the prophylaxis of influenza in human.

Disclosures
S. Shano, Shionogi & Co., Ltd.: Employee, Salary. K. Fukao, Shionogi & Co., Ltd.: Employee, Salary. T. Noshi, Shionogi & Co., Ltd.: Employee, Salary. K. Sato, Shionogi & Co., Ltd.: Employee, Salary. M. Sakuramoto, Shionogi & Co., Ltd.: Employee, Salary. K. Baba, Shionogi TechnoAdvance Research & Co., Ltd.: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. A. Naito, Shionogi & Co., Ltd.: Employee, Salary.
1344. Ridinilazole (RDZ) for Clostridium difficile Infection (CDI): Impact of Diagnostic Method on Outcomes From a Phase 2 Clinical Trial
Authors: Vickers Richard , Chowdhury Sumita , Wilcox Mark 
Published: November 2018

Abstract

Background
Diagnosis of CDI includes fecal detection of a C. difficile toxigenic strain (TS) or free toxins (FT). TS detection does not distinguish infection from colonization. Guidelines recommend an FT test be part of diagnostic algorithms. Here we report outcome differences, based on diagnostic method at enrollment, from a Phase 2 clinical trial of RDZ, a novel CDI antibiotic designed to treat CDI and reduce recurrence of CDI (rCDI).

Methods
This double-blind study randomized 100 patients 1:1 to 10 days RDZ 200 mg BID or vancomycin (VAN) 125 mg QID treatment. Subjects were enrolled with CDI symptoms and a positive diagnostic result (FT or TS). Baseline (BL) stool samples were assessed for the presence of FT. All subjects entered the intent to treat (ITT) population; those subjects positive for FT entered a modified ITT (mITT), the primary analysis population. Primary endpoint was sustained clinical response (SCR) defined as cure at end of therapy and no rCDI for the next 30 days. rCDI was defined as CDI symptoms, a positive diagnostic test and need for therapy; a sensitivity analysis considered positive FT rCDI cases. BL fecal concentrations of lactoferrin and calprotectin were determined by enzyme immunoassay.

Results
Of 100 subjects enrolled, 69 (36 RDZ: 33 VAN) were FT positive at BL. RDZ compared with VAN recipients had improved SCR rates via reduced rCDI. Absolute differences in SCR between RDZ and VAN (prespecified 90% CI) for MITT (FT positive) and ITT subjects were 24.3% (3.1, 39.1) and 14.0% (−1.8, 28.8), respectively. Absolute SCR differences between the MITT and ITT subjects from the sensitivity analysis were 26.2% (4.6, 40.6) and 14.3% (−1.7, 29.1). Median BL calprotectin and lactoferrin levels (µg/mL) were significantly higher for FT positive subjects at 1,002 and 87, than for FT negative subjects at 53 and 4, respectively.

Conclusion
RDZ showed improved SCR in comparison with VAN. Treatment differences were greater in MITT subjects. Lower SCR improvement in RDZ ITT subjects is likely due to enrollment of some colonized rather than infected subjects; this explanation is supported by higher calprotectin and lactoferrin levels in FT-positive samples. These data demonstrate the importance of FT testing in-line with CDI guideline recommendations.

Disclosures
R. Vickers, Summit Therapeutics: Employee, Salary and Stock options. S. Chowdhury, Summit Therapeutics: Employee, Salary and Stock options. M. Wilcox, Summit Therapeutics: Consultant, Research Contractor and Scientific. Advisor, Consulting fee, Research grant and Research support.