bluuebunny/crossref_metadata_2025 huggingface dataset:
1311. Incorporating an “Escape Room” Game Design in Infectious Diseases Instruction
Authors: Cotner Sarah , Smith Kelly M , Simpson Leah , Burgess David S , Cain Jeffrey
Published: November 2018

Background

As health professions education evolves toward active learning environments, interest in using games as an educational tool is increasing. One contemporary commercial game that has design potential for learning activities is an “escape” or “breakout” room. Escape rooms are live-action games where teams of players work to achieve a common goal in a set amount of time. Limited literature is available assessing this type of gaming format for education design. This study investigated the design and implementation of an escape room learning activity in a third-year pharmacy infectious disease elective course at the University of Kentucky College of Pharmacy.

Methods

During a Gram-positive antimicrobial resistance module, third-year pharmacy students participated in both patient case-based instruction and an escape room learning activity. Three IRB-approved surveys were distributed electronically to students; the first was completed prior to class and functioned as a standard teaching tool to assess mastery of content based on pre-assigned reading and previous coursework. Two surveys were completed after the session to assess knowledge and perceptions gained during each learning activity. Students answered multiple-choice knowledge-based questions and then responded to five statements using a Likert scale from 1 to 7 (1 = Not at all, 4 = Somewhat, and 7 = Very much) to indicate perceptions of each instructional activity.

Results

Nineteen students participated in the study. The mean correct scores for knowledge-based assessment were 90.5% in the pre-class survey, 82.1% in the post-case survey, and 90.5% in the post-escape room survey. There was an overall positive perception of both learning activities based on results of the survey questions. The escape room learning activity was preferred by 18 of 19 students (94.7%), but only 11 of 19 (57.9%) indicated they learned better from the escape room.

Conclusion

This study illustrates an escape room designed to meet lecture learning objectives is a feasible active learning technique. While students demonstrated knowledge gained from the activity and indicated positive perceptions, this approach warrants further evaluation.

Disclosures

All authors: No reported disclosures.
1317. Online Simulation-Based Education to Improve Primary Care Providers’ Knowledge About Best Practices in HIV Preexposure Prophylaxis Care
Authors: Gardner Allison , Evans David , McCord Alan , Krakower Douglas
Published: November 2018

Background

Primary care providers’ (PCPs’) lack of knowledge about and use of pre-exposure prophylaxis (PrEP) represent important barriers to its effective implementation on a national scale. To address these barriers, a collaboration of infectious diseases clinicians, patient advocates, and continuing medical education (CME) specialists developed and tested an educational intervention for PCPs to increase their knowledge about best practices for providing PrEP-related care.

Methods

An interactive, online CME-accredited simulation prompted PCPs to make clinical decisions about a hypothetical case of a 44-year-old African-American man seeking treatment for rectal gonorrhea who thus had indications for PrEP. The intervention included real-time educational feedback on clinical decisions and an opportunity to revisit suboptimal care decisions after feedback. PCPs were recruited via email and links on CME/patient advocacy websites and public health listservs. Outcomes included proportions of learners selecting correct answers prior to and after receiving feedback on their decisions.

Results

During October 2017–April 2018, 234 PCPs (88% physicians, 7% NP, 5% PA) completed the simulation for a total of 4,701 unique clinical decisions. Less than half (45%) of PCPs elicited a comprehensive sexual health history to begin the visit, which improved to 83% after feedback. Two-thirds (67%) of PCPs sought permission before asking about sexual behaviors, which increased to 82% after feedback. Nearly one-quarter of PCPs (24%) needed corrective action to nonjudgmentally ask about condom use. Almost all PCPs (91%) identified that PrEP was appropriate for the case patient on their first attempt. However, only 54% of PCPs initially selected all recommended baseline laboratory tests for PrEP; 75% did so after feedback. Of providers recommending PrEP, 29% selected regimens not FDA approved for this indication.

Conclusion

Many PCPs participating in an online simulation enacted clinical decisions that were inconsistent with best practices for providing PrEP-related care, but hypothetical care decisions improved after real-time educational feedback. Future studies to test the impact of this educational intervention on clinical practices are warranted.

Disclosures

D. Evans, Project Inform: Employee, Educational grant. A. McCord, Project Inform: Employee, Educational grant. D. Krakower, Gilead Sciences: Grant Investigator, Research grant.
1319. Examining PrEP Knowledge and Prescribing Likelihood Among Medical Residents Before and After PrEP Education
Authors: Christian Elizabeth , Craig Wendy , Thakarar Kinna
Published: November 2018

Background

Pre-exposure prophylaxis (PrEP) is effective for HIV prevention, but prescribing rates remain low. We examined the effect of an educational intervention on PrEP knowledge and prescribing likelihood among medical residents.

Methods

This was a prospective study using a convenience sample of Internal Medicine and Internal Medicine-Pediatrics residents at a tertiary care center in Portland, Maine. Participants attended a resident-led teaching session on PrEP and completed pre- and post-session surveys. PrEP knowledge was measured with five questions (definition, evidence, patient selection criteria, medication choice, and guidelines), and prescribing likelihood was assessed on a Likert scale. Participants identified motivating factors and barriers to prescribing. Survey data were analyzed with McNemar’s test or a paired Student’s t test as appropriate.

Results

Thirty residents completed the study; of these, 24 (83%) had at least 1 patient that they considered at high risk for HIV, and 14 (46%) reported having >5 such patients. None had ever prescribed PrEP. Average PrEP knowledge score increased after the intervention (pre = 2.33 vs. post = 4.1, P < 0.001). After the intervention, more participants reported that they would be likely to prescribe PrEP (pre = 76% vs. post = 90%, P = 0.014), fewer identified unfamiliarity with PrEP guidelines as a barrier (pre = 73% vs. post = 27%, P < 0.001), and Òother residents are prescribing PrEPÓ became a significant motivating factor (pre = 47% vs. post = 70%, P = 0.04). Preceptor comfort with prescribing PrEP was a consistently important influence on prescribing likelihood (90% vs. 82%, P = 0.22).

Conclusion

Familiarity with PrEP is relevant to resident practice, and an educational intervention is effective in the short term for addressing inadequate knowledge as a barrier to offering PrEP. Resident practice is influenced by preceptors and peers, suggesting that it may be helpful to include attending physicians in future PrEP education efforts at our institution.

Disclosures

All authors: No reported disclosures.
1328. Medical Education in an Epidemic: Historical Lessons From the Early Days of HIV in America (1982–1986)
Authors: Koretzky Maya Overby
Published: November 2018

Background

Much historical work has investigated the impact of HIV on patient rights, American culture, and medical research; however, there is little scholarship on the impact of HIV on medical education. This study asks how the process of training at the epicenter of an epidemic disease that was poorly understood, incurable, and contagious shaped a cohort of physicians’ experience of residency, beliefs about the role of the doctor in society, and their approach to practicing medicine.

Methods

Members of the University of California San Francisco (UCSF) intern classes of 1982 and 1983 were interviewed, as well as individuals who were young faculty at San Francisco hospitals in the 1980s. Other sources included academic publications from the 1980s on HIV and medical education, archival documents, nursing and volunteer communications books from the SF General Hospital AIDS Ward, and patient ephemera such as thank you notes and obituaries.

Results

These interviews and documents highlight themes of commitment to care for HIV patients regardless of risk, lack of formal institutional support for residents engaged in HIV care, and differences in professional norms that allowed nurses and volunteers access to modes of reflection that were unavailable to trainee physicians. For residents, the day to day experience of the HIV epidemic became an important locus for a narrative of medical professionalism and resilience that continues to animate medical education today. Provider narratives about the encounter with HIV served a parallel function to the creation of HIV clinics and public health programs—both were interventions that made HIV into an intelligible cultural and biological entity that could be managed by the medical profession.

Conclusion

Using the HIV epidemic in San Francisco as a historical example, this project argues that formalizing narrative practices by setting aside time for journaling and verbal reflection in residency and fellowship training can build resilience and prevent burnout. Historical narratives of provider experience, like the oral histories collected in this project, may also be valuable in undergraduate medical education to generate discussion about professional ethics and the responsibilities of providers in an epidemic.

Disclosures

All authors: No reported disclosures.
1345. Comparative Activity of Plazomicin and Other Aminoglycosides Against Enterobacteriaceae Isolates From Various Infection Sources From Hospitalized Patients in the United States
Authors: Castanheira Mariana , Streit Jennifer M , Serio Alisa W , Krause Kevin M , Flamm Robert K
Published: November 2018

Background

Plazomicin is a next-generation aminoglycoside that is currently under review at the United States Food and Drug Administration for complicated urinary tract infections (cUTIs), including acute pyelonephritis, and bloodstream infections (BSIs) due to certain Enterobacteriaceae (ENT) in patients who have limited or no alternative treatment options. We evaluated the activity of plazomicin and aminoglycosides against ENT isolates collected in US hospitals during 2014 to 2017 by site of infection.

Methods

A total of 8,510 ENT isolates were collected from BSIs (2,133), pneumonia in hospitalized patients (PIHP; 1,826), skin and skin structure infections (SSSIs; 1,155), intra-abdominal infections (IAIs; 731), UTIs (2,508), and other or unknown infection sites (others; 157) in 71 US hospitals during 2014 to 2017. Isolates were susceptibility (S) tested by reference broth microdilution methods and results were interpreted using CLSI breakpoints.

Results

Plazomicin (MIC50/90 ranges, 0.25–0.5/1–2 µg/mL) inhibited 98.8–99.9% of the ENT isolates at ≤4 µg/mL across all infection types (figure). At ≤4 µg/mL, plazomicin inhibited 93.8–100% of the carbapenem-resistant ENT (CRE) isolates stratified by infection type. The S rates for amikacin ranged from 98.7% to 99.7% against ENT isolates overall. However, amikacin S rates for CRE ranged from 53.1% for UTI to 100% for IAI isolates. Gentamicin (89.2–93.6%S) and tobramycin (88.8–94.3%S) were slightly less active than plazomicin and amikacin against the ENT isolates stratified by infection source. Gentamicin S rates against CRE isolates ranged from 43.8% to 66.7% while tobramycin inhibited <45% of the CRE isolates from the different infection sources.

Conclusion

The activity of plazomicin and amikacin was similar against ENT isolates from US hospitals and did not vary by infection type; however, amikacin activity against CRE isolates varied by infection source while plazomicin remained active against CRE isolates regardless of infection source. These results highlight the potential role of plazomicin for treating serious infections caused by CRE. This project was partially funded under BARDA Contract No. HHSO100201000046C.

Disclosures

M. Castanheira, Achaogen: Research Contractor, Research support. J. M. Streit, Achaogen: Research Contractor, Research support. A. W. Serio, Achaogen: Employee, Salary. K. M. Krause, Achaogen: Employee, Salary. R. K. Flamm, Achaogen: Research Contractor, Research support.
1350. Therapeutic Effects of Baloxavir Marboxil against Influenza A Virus Infection in Ferrets
Authors: Kitano Mitsutaka , Matsuzaki Takanobu , Oka Ryoko , Baba Kaoru , Noda Takahiro , Yoshida Yuki , Sato Kenji , Yoshida Ryu , Sato Akihiko , Kamimori Hiroshi , Shishido Takao , Naito and Akira
Published: November 2018

Background

Baloxavir marboxil (BXM) is a novel small molecule inhibitor of cap-dependent endonuclease that is essential for influenza virus transcription and replication. In this study, pharmacokinetic profiles of BXM and baloxavir acid (BXA), an active form of BXM, were first examined in ferrets, and then the therapeutic effects of BXM against influenza A virus infection were compared with that of oseltamivir phosphate in ferrets.

Methods

The plasma exposure of BXA and BXM was examined after a single oral administration of BXM at doses of 10 and 30 mg/kg. The concentrations in plasma were determined by liquid chromatography-tandem mass spectrometry(LC/MS/MS). For efficacy study, ferrets infected intranasally with A/Kadoma/2006 (H1N1) were administrated 10 or 30 mg/kg of BXM orally twice daily for 1 day, starting at 1 day post-infection (p.i.) or administrated 10 mg/kg of BXM orally twice daily for 1 day, starting at 2 days p.i.. Oseltamivir phosphate was administered at doses of 5 mg/kg orally twice daily for 2 days as a comparison. The virus titer in the nasal washes and body temperature change were monitored during infection.

Results

BXA was detected in ferret plasma after a single oral administration of BXM at 10 and 30 mg/kg, in more than a dose-proportional manner. When the treatment was initiated at 1 day p.i., BXM at 10 and 30 mg/kg showed reduction of virus titer to an undetectable level on day 2 p.i. and statistically significant reduction in virus titer over time from day 2 to 3 p.i. compared with vehicle and oseltamivir phosphate. Moreover, the change of body temperature over time from 8 hours after the first administration to 3 days p.i. was significantly lower in BXM at 10 and 30 mg/kg than vehicle and oseltamivir phosphate. These effects were also observed in ferrets treated with BXM at 10 mg/kg even when administered at 2 day p.i. where ferret exhibit fever that is more than 1 degree higher than on 1 day p.i..

Conclusion

Single-day oral administration of BXM had beneficial effects on viral titer and symptoms in ferrets infected with influenza A virus, which were superior to those observed with oseltamivir phosphate and vehicle.

Disclosures

M. Kitano, Shionogi & Co., Ltd.: Employee, Salary. T. Matsuzaki, Shionogi & Co., Ltd.: Employee, Salary. R. Oka, Shionogi & Co., Ltd.: Employee, Salary. K. Baba, Shionogi TechnoAdvance Research & Co., Ltd.: Employee, Salary. T. Noda, Shionogi TechnoAdvance Research & Co., Ltd.: Employee, Salary. Y. Yoshida, Shionogi & Co., Ltd.: Employee, Salary. K. Sato, Shionogi & Co., Ltd.: Employee, Salary. R. Yoshida, Shionogi & Co., Ltd.: Employee, Salary. A. Sato, Shionogi & Co., Ltd.: Employee, Salary. H. Kamimori, Shionogi & Co., Ltd.: Employee, Salary.

T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. A. Naito, Shionogi & Co., Ltd.: Employee, Salary.
1356. Improvement in Quality of Life for Adults With Acute Bacterial Skin and Skin Structure Infections Following Treatment With Omadacycline or Linezolid
Authors: Tzanis Evan , Chitra Surya , Curran Marla , McGovern Paul , Hinahara Jordan , Goss Thomas
Published: November 2018

Background

The appearance of multidrug-resistant Gram-positive bacteria is a major challenge in clinical care. Omadacycline is the first aminomethylcycline antibiotic (semisynthetic compounds related to tetracyclines) in late-stage clinical development for acute bacterial skin and skin structure infections (ABSSSI), and demonstrates potent in vitro activity against many pathogens.

Methods

Seven hundred thirty-five patients were enrolled in the OASIS-2 randomized controlled trial comparing omadacycline and linezolid for the treatment of adult subjects with ABSSSI known or suspected to be due to a Gram-positive pathogen, with 368 and 367 enrolled in each group, respectively. Subjects completed the 36-Item Short Form Health Survey Version 2 (SF-36v2), a validated questionnaire on physical and mental health, at both screening and post-treatment evaluation. Results of the SF-36v2 were analyzed in accordance with established norm-based standards for the survey (Ware 2000) for the intention-to-treat population.

Results

Subjects who received omadacycline experienced a 3.25 point mean improvement in overall physical health (P < 0.001, Figure 1) and reported significant improvements across all but one component parameter of overall physical and mental health, including physical functioning, bodily pain, role physical, vitality, role emotional, mental health, and social functioning (Figure 2). In contrast, while overall physical health improved for subjects who received linezolid, the improvement in vitality, role emotional, mental health, and general health was not significant (Figure 2). Although omadacycline achieved greater increase from baseline than linezolid across all domains analyzed, the difference in scores was not statistically significant at the P < 0.05 level (Figure 1).

Conclusion

Omadacycline provides significant improvement in the physical component of quality of life over baseline for adult subjects with ABSSSI known or suspected to be due to a Gram-positive pathogen. Although the OASIS-2 trial was neither designed nor powered to measure differences in quality of life following treatment, trends identified in this analysis merit further investigation.

References

1. Ware JE. SF-36 Health Survey Update. SPINE 2000; 25(24); 3130–3139.

Disclosures

E. Tzanis, Paratek Pharmaceuticals: Employee, Salary. M. Curran, Paratek Pharmaceuticals: Employee, Salary. P. McGovern, Paratek Pharmaceuticals: Employee, Salary. J. Hinahara, Paratek Pharmaceuticals: Consultant, Consulting fee. T. Goss, Paratek Pharmaceuticals: Consultant, Consulting fee.
1371. Safety, Tolerability, and Pharmacokinetics of Multiple Doses of TP-6076, a Novel, Fully Synthetic Tetracycline, in a Phase 1 Study
Authors: Tsai Larry , Moore Alison
Published: November 2018

Background

TP-6076 is a novel, fully synthetic tetracycline being developed for the treatment of serious bacterial infections, including those caused by multidrug-resistant Acinetobacter baumannii. TP-6076 has demonstrated potent activity in vitro against carbapenem-resistant strains of A. baumannii, with MIC90 64 times lower compared with tigecycline and 256 times lower compared with minocycline. We now report the results of a multiple ascending dose study in normal healthy volunteers.

Methods

This was a phase 1, single-site, randomized, double-blind, placebo-controlled dose-escalating, multiple dose study in healthy adults who met the inclusion/exclusion criteria and provided informed consent prior to any study procedure. Cohorts of eight subjects each (six active and two placebo) received daily doses of 6.0 to 40.0 mg TP-6076 or placebo for 7 days. Plasma and urine samples for pharmacokinetic (PK) analyses were collected starting immediately prior to dosing until 96 hours after the last dose. Safety was assessed through collection of adverse events (AEs), clinical laboratories, vital signs, ECG, and physical examination data.

Results

The geometric mean derived PK parameters for TP-6076 were:

There were no serious or severe AEs reported. The most frequently reported AEs were gastrointestinal events, including nausea and vomiting, and localized infusion site reactions. There were no clinically significant changes in clinical laboratory values, ECG parameters, or physical examination findings.

Conclusion

Following multiple IV doses of TP-6076, plasma exposure increased as dose increased. Multiple IV doses of TP-6076 were generally well tolerated, with higher gastrointestinal adverse event rates in the higher dose groups.

Disclosures

L. Tsai, Tetraphase Pharmaceuticals: Employee and Shareholder, Salary. A. Moore, Tetraphase Pharmaceuticals: Employee, Salary.
1380. Effect of Absolute Body Weight on Clinical Outcomes of Obese Patients Treated with Cefepime
Authors: Wagner Jamie L , Morrison Austin R , Loper J Taylor , Barber Katie E , Stover Kayla R
Published: November 2018

Background

Differences in pharmacokinetic and pharmacodynamic parameters for obese (OB) patients compared with nonobese (NOB) patients are well known, but drug safety and efficacy when using package insert dosing remain unclear. The purpose of this study was to evaluate the clinical outcomes of cefepime (FEP) for OB patients vs. NOB patients.

Methods

This retrospective cohort included inpatient adults ≥18 years treated with FEP monotherapy for ≥72 hours between July 2015 and July 2017. Exclusion criteria were source control not achieved within 72 hours and polymicrobial infections requiring > 1 antibiotic for definitive therapy. Additional data collected were demographics, comorbid conditions, laboratory markers, site of infection, and microbiology. The primary endpoint was clinical treatment failure, defined as change in definitive therapy at >72 hours due to clinical worsening, leukocytosis (WBC > 10 × 109/L) for >72 hours after treatment initiation, fever (single temperature >100.9°F) after >72 hours of treatment initiation, or readmission within 30 days due to re-infection. Secondary outcomes were 30-day inpatient all-cause mortality and 30-day readmission.

Results

One hundred fourteen subjects were included (58 OB; 56 NOB). Median (IQR) age 58[46–66] years; 66(58%) males. Median [IQR] weight 107[95–124] kg OB patients; 75[63–84] kg NOB patients. Median Charlson score was 3[2–5] (P = 0.478). Sixty-two percent OB patients vs. 46% NOB patients experienced a respiratory infection (P = 0.094); 28% OB patients vs. 39% NOB patients experienced a urinary tract infection (P = 0.185). 62% OB patients and 59% NOB patients received FEP 1g q8h (P = 0.732). Most common minimum inhibitory concentration (MIC) in both groups was 1 mg/L (74% OB vs. 83% NOB; P = 0.289). Clinical failure occurred in 52% (67% OB vs. 36% NOB; P = 0.001). OB patients more likely to need a second antibiotic (31% vs. 14%; P = 0.033) and have persistent leukocytosis (50% vs. 30%; P = 0.033). Inpatient all-cause mortality occurred in 17% (22% OB vs. 12% NOB; P = 0.164). 72% of patients were not readmitted within 30 days of discharge.

Conclusion

OB patients experienced higher treatment failure than NOB patients. Further examination is needed to assess impact of FEP dose and organism MIC on clinical failure in OB patients.

Disclosures

All authors: No reported disclosures.
1398. β-Lactam Probability of Target Attainment (PTA) and Penetration into Epithelial Lining Fluid (ELF) Based on Multiple Bronchoalveolar Lavage (BAL) Sampling Time Points in a Swine Pneumonia Model
Authors: Motos Ana , Kuti Joseph L , Bassi Gianluigi Li , Torres Antoni , Nicolau David P
Published: November 2018

Background

Defining ELF concentrations is desired for antibiotics developed for pneumonia. For ethical reasons, BAL sampling in humans is routinely done at a single time point, thereby creating ambiguity in the precise ELF profile. It is unknown if additional sampling of the ELF would lead to more accurate estimates of exposure. The swine pneumonia model was used to characterize the full ELF profiles (5-BAL) of two β-lactams for comparison with models employing 1-BAL (1B) and 2-BAL (2B) sampling time points only.

Methods

Sixteen ventilated swine were infected with Pseudomonas aeruginosa to establish pneumonia and then treated for 72 hours with ceftolozane/tazobactam (C/T) 50 mg/kg q8h (n = 8) or piperacillin/tazobactam (TZP) 200 mg/kg q8h (n = 8). Plasma and BAL concentrations were measured in each swine at 1, 2, 4, 6, and 8 hours after the first dose. Urea correction was used to calculate ELF values. Ceftolozane and piperacillin plasma and ELF data were fitted to a two compartment model using the nonparametric adaptive grid program in Pmetrics. Hypothetical models were refitted after randomly selecting either 1B or 2B sampling time points from each swine. A 5,000 subject Monte-Carlo simulation was performed for each model to define PTA (60% free time above the MIC) and ELF penetration [area under the curve in ELF (AUCELF) vs. free AUCplasma]. The KS-test was used to analyze distribution differences, reporting maximum vertical deviation (D) as percent difference; D < 20% was defined as negligible.

Results

Thirty-two C/T and 34 TZP plasma samples and 29 and 32 BAL samples were available for the full model, respectively; 1B and 2B sampling models used eight and 16 BAL samples. All models adequately fitted the data. C/T PTA at 4 mg/L was 94.8, 96.1, and 98.0%, for the full, 1B and 2B models. TZP PTA at 16 mg/L was 55.8, 46.8, and 46.7%, respectively. C/T median [interquartile range] penetration differences were negligible between the full (65% [25––109]) and 1B (72% [45––125], D = 15%) or 2B models (62% [32––111], D = 6%). TZP penetration differences were also minimal between the full (32% [9––67]) and 1B (17% [5––49], D = 18%) or 2B models (27% [9––44], D = 15%).

Conclusion

These data suggest that antibiotic ELF models constructed from a single BAL time point result in similar exposure estimates to full ELF profiles.

Disclosures

G. Li Bassi, MSD: Grant Investigator, Grant recipient. A. Torres, MSD: Grant Investigator, Grant recipient.
668. Clinical Spectrum of Powassan Virus Infection in Patients Presenting with Suspected Acute Tick-Borne Illness From a Lyme-Endemic Focus in the Midwest
Authors: Kehl Sue , Callister Steven , Jobe Dean , Thomm Angela , Yin Ziyan , Kim Soyoung , Pratt Phillip , Knox Konstance
Published: November 2018

Background

Powassan virus (POWV) is the North American member of the tick-borne encephalitis complex of viruses. The potential for concurrent transmission with other tick-borne pathogens, particularly the Lyme disease agent Borrelia burgdorferi, is under studied. To better understand the clinical spectrum of POWV infection patient health records were reviewed and laboratory studies performed to evaluate the frequency of tick-borne pathogen exposure in patients presenting with suspected acute tick-borne illness (TBI) from a Lyme-endemic focus in the Midwest.

Methods

One hundred and thirty-five samples selected from patients seen at Gundersen Health System presenting during 2016 with Lyme-like symptoms were tested for Anaplasmosis, Babesiosis, Lyme disease and POWV. PCR testing was performed for Anaplasma and Babesia. Serologic testing for B. burgdorferi was performed using two-tier serologic testing. POWV infection was confirmed by POWV-EIA/IFA (Coppe Laboratories). IRB approval was obtained.

Results

Anaplasma infection was seen in 44/88 (50%), Babesia infection in 5/67 (7.5%), Lyme disease in 45/135 (33.3%) and POWV infection in 16/132 (12.1%) patients. Co-infections were seen in 21/135 (15.5%) patients. Patients with Babesia more often presented with anemia, myalgia and decreased appetite. Patients with Anaplasma presented with fever, chills/sweats, nausea/vomiting, rash, elevated liver function tests, thrombocytopenia, leukopenia, and remembered the tick exposure. Lyme disease patients complained of fatigue, rash, chills/sweats, headache and remembered the tick exposure. Co-infection with both Lyme and Powassan virus was seen in 10/45 (23%) of patients. Patients with Lyme, Powassan virus or co-infection had no other significant difference in symptoms.

Conclusion

POWV infection is more prevalent in the Midwest than previously appreciated. Clinical data suggest that symptoms of POWV infection may be indistinguishable from those of Lyme disease, requiring laboratory testing for proper TBD diagnosis and avoidance of unnecessary antibiotic use. The high rate of POWV co-occurrence with Lyme disease may have relevance for patient outcomes and warrants further investigation.

Disclosures

S. Kehl, Coppe Laboratories: Consultant, Consulting fee. A. Thomm, Coppe Laboratory: Employee, Salary. P. Pratt, Coppe Laboratory: Employee, Salary. K. Knox, Coppe Laboratory: Owner, Equity as compensation.
675. Current Physician Knowledge, Attitudes, and Clinical Practice Regarding Legionnaires’ Disease in the Aftermath of the Flint Water Crisis in Genesee County, Michigan
Authors: Alaga Katanya C , Konja Jewel M , Salim Abdulbaset , Levine Pete , Smith Sherry , Zervos Marcus J , Kilgore Paul
Published: November 2018

Background

Legionnaires’ disease (LD) is a respiratory illness caused by the inhalation of aerosolized water contaminated with Legionella bacteria. For reasons not yet understood, the incidence of LD has steadily increased across the United States during the past 10 years. In 2014 and 2015, the City of Flint in Genesee County (GC), Michigan underwent a change in the city’s water source, which resulted in the third largest recorded LD outbreak in American history and over 100,000 residents being exposed to contaminated water. In order to reduce the incidence of LD in at-risk populations it is imperative that we evaluate and improve LD knowledge and clinical practice among healthcare personnel.

Methods

This investigation surveyed clinicians practicing in Genesee County who are also members of the Genesee County Medical Society (GCMS). A survey was designed to assess current clinical knowledge, attitudes, and practices related to LD, in addition to measuring the uptake and utility of the LD clinical guidelines. The survey and the LD clinical guidelines were distributed to all GCMS members over a 6-month period. Prompts to complete the survey using Qualtrics programming were emailed to GCMS members and posted in the GCMS monthly bulletin. In addition, surveys were distributed to members at GCMS meetings. Completed responses were entered into Qualtrics software and exported into MS Excel and SPSS statistical software for analysis.

Results

In total, 95 healthcare personnel responded. Of those surveyed, 79.5% have been in practice for more than 10 years and 55% identified as practicing in family, internal or emergency medicine. Despite, the well-publicized LD outbreak in GC, 45% of respondents did not believe or were unsure if LD was a current public health issue, and 65% have either not received, have received but are not interested, or have received but not read the LD clinical guidelines. Despite this, 47% and 61% of respondents were able to correctly identify the symptoms and risk factors for LD, respectively. In addition, 34% of participants believe that drinking tap water is a risk factor for contracting LD.

Conclusion

This survey underscores the continuing need for comprehensive physician education to improve the clinical recognition and evaluation of patients with LD.

Disclosures

All authors: No reported disclosures.
677. Using a Multisectoral One Health Approach to Prioritize Zoonotic Diseases in the United States
Authors: Krishnasamy Vikram , Behravesh Casey Barton , Varela Kate , Goryoka Grace , Oussayef Nadia , Rooney Jane , Dutcher Tracey , Bond Elaine , Hopkins M Camille , Gibbs Samantha
Published: November 2018

Background

Emerging and endemic zoonoses continue to have adverse global impacts. One Health approaches promoting multisectoral, transdisciplinary collaboration are important methods to address zoonoses threats through disease surveillance, prevention, control, and response. We conducted a One Health Zoonotic Disease Prioritization (OHZDP) workshop in the United States (US) to identify zoonotic diseases of greatest national concern that should be jointly addressed by the Centers for Disease Control (CDC), US Department of Agriculture (USDA), Department of the Interior, and partners.

Methods

We used CDC’s OHZDP tool to prioritize zoonoses. Workshop participants selected criteria for prioritization, and developed questions and weights for each criterion. Questions were answered using available literature and expert opinion with subsequent scoring resulting in a ranked zoonotic disease list. After agreeing on a final prioritized disease list, participants used components of the One Health Systems Mapping and Analysis Resource Toolkit, developed by USDA and University of Minnesota, to review multidisciplinary coordination processes for the prioritized zoonotic diseases.

Results

Participants selected epidemic or pandemic potential, disease severity, economic impact, introduction or increased transmission potential, and national security as criteria to prioritize 56 zoonoses. The eight prioritized zoonotic diseases for the US were zoonotic influenzas, salmonellosis, West Nile virus, plague, emerging coronaviruses (e.g., SARS, MERS), rabies, brucellosis, and Lyme disease. Agencies then discussed recommendations to enhance One Health approaches to surveillance, response, prevention, and control of the prioritized zoonoses. Key themes and next steps for further implementation of One Health approaches were identified.

Conclusion

This OHZDP workshop represents the first use of a One Health approach to zoonotic disease prioritization in the United States. It is a critical step forward in US government agency collaboration using One Health approaches. Further, the workshop created a foundation for future US government One Health systems strengthening for the prioritized zoonoses.

Disclosures

All authors: No reported disclosures.
681. Epidemiology and Outcomes of Patients with Carbapenem-Resistant Bloodstream Infection in United States Hospitals, 2010–2015
Authors: Echols Roger , Corvino Frank , Cai Bin , Lodise Thomas P
Published: November 2018

Background

Carbapenem resistance (CR) in patients with Gram-negative (GN) bloodstream infections (BSI) presents a mounting therapeutic challenge. To gain a better understanding of CR among patients in US hospitals, we explored their characteristics and outcomes.

Methods

We performed a retrospective cohort analysis of consecutive adult patients (age ≥18 years) with a positive blood culture for GN pathogens (11 most prevalent pathogens reported in ~53,811 study patient samples), hospitalized in one of 181 institutions contributing microbiology data to the Premier Healthcare Database (October 2010–September 2015). We compared patients with CR vs. carbapenem-susceptible (CS) BSIs based on their characteristics and outcomes. Primary outcome was mortality, and secondary outcomes included post-index culture hospital and ICU lengths of stay (LOS), and likelihood of being discharged home.

Results

Of the ~53,811 study patient samples, 46,381 patients had a GN BSI, with the prevalence of CR occurring at 3.5% (n = 1,602). Compared with patients with CS, those with CR were younger (mean/SD 60.4/17.1 vs. 67.4/16.4 years, P < 0.01), more likely to be male (52.8% vs. 45.9%, P < 0.01), black (22.7% vs. 17.7%, P < 0.01), and had Medicaid as a payor (18.1% vs. 10.9%, P < 0.01). The mean/SD Charlson Comorbidity Index was higher in CR than CS group (2.9/2.5 vs. 2.3/2.5, P < 0.01). Crude mortality was also higher (20.6% vs. 9.7%, P < 0.01) in the setting of CR than CS, as were unadjusted median (IQR) post-index culture hospital (9 [6, 15] vs. 7 [5, 10] days, P < 0.01), and ICU (5 [2, 11] vs. 3 [2, 6] days, P < 0.01) LOS. Patients with CR BSI were less likely to be discharged home than those with CS (32.7% vs. 53.8%, P < 0.001).

Conclusion

Patients with CR BSIs have lower likelihood of surviving hospitalization or being discharged home, and longer post-index culture hospital and ICU LOS, compared with those with CS BSIs. This highlights the need for better and more preventive and therapeutic strategies aimed at combating GN CR.

Disclosures

A. F. Shorr, Astellas: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium

Cidara: Consultant, Consulting fee. Merck & Co.: Consultant and Speaker’s Bureau, Consulting fee, Research support and Speaker honorarium. T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee.
682. The Changing Epidemiology of Bacterial Meningitis During 2015–2017 in Turkey: A Hospital-Based Prospective Surveillance Study
Authors: Ceyhan Mehmet , Ozsurekci Yasemin , Bayhan Cihangül , Gurler Nezahat , Sali Enes , Emiroglu Melike Keser , Öz Fatma Nur , Camcioglu Yıldız , Salman Nuran , Kurugol Zafer , Akisoglu Havva Ozlem Altay , Tuygun Nilden , Belet Nursen , Ulusoy Emel , Dinleyici Ener Cagri , Tezer Hasan , Parlakay Aslınur , Karbuz Adem , Aktar Fesih , Hacimustafaoglu Mustafa , Basaranoglu Sevgen Tanır , Aykac Kubra , Kocabas Emine , Gundeslioglu Ozlem Ozgur , Hatipoglu Nevin , Hatipoglu Sadık Sami , Şensoy Gülnar , Oncel Eda Karadag , Solmaz Mehmet Ali , Kara Soner Sertan , Çelebi Solmaz , Çelik Ümit , Metin Özge , Bozdemir Şefika , Devrim Ilker , Kara Ahu , Sütçü Murat
Published: November 2018

Background

The etiology of bacterial meningitis in Turkey has been changed after the implementation of conjugated vaccines against Streptococcus pneumonia and Haemophilus influenzae type b (Hib) in Turkish national immunization schedule. Methods. This prospective study was conducted in 25 hospitals located seven regions of Turkey (representing 30% of Turkey population) and children aged between 1 month and 18 years with suspected meningitis and hospitalized were included. Cerebrospinal fluid samples were collected and bacterial identification was made according to the multiplex PCR assay results. Results. During the study period, 927 children were hospitalized for suspected meningitis and Hib (n:1), S. pneumonia (n:17) and Neisseria meningitidis (n:59) were detected in 77 samples (Figure 1, Table 1). During 2015–2016, N. meningitidis serogroup W, B, A, Y, X frequencies were as 5 (13.9%), 16 (44.4%), 1 (2.8%), 1 (2.8%), 1 (2.8%), respectively. There were 12 nongroupable N. meningitidis samples and serogroup C was not detected. In 2017, of meningococcal meningitis serogroup B, W, A, Y and X were identified in two (8.7%), 15 (65.2%), two (8.7%), 1 (4.3%) and 1 (4.3%) cases, respectively (Figure 2). There were four deaths in this study period, all of them were caused by N. meningitidis serogroup B and three of them were under 1 year old. Conclusion. The epidemiology of meningococcal diseases has been varied in time with or without any apparent reasons. Hajj is a well-known cause for serogroup W epidemics and serogorup W was the most common cause of meningitis in Turkey during 2009–2014 as in other Middle East countries. After the impact of serogroup W epidemics related to Hajj seen in 2010’s was diminished, serogroup B has been leading cause of childhood meningitis since 2015. In countries affected from Hajj like Turkey, vaccination of children with serogroup B meningococcal vaccine as well as quadrivalentconjugated vaccine seems to be very important. It should be kept in mind that meningococcal epidemiology is dynamic and needed to be closely monitored to detect changes in years

Disclosures

All authors: No reported disclosures.
705. Four Superbugs Isolated From a Single Patient in the United States: E. coli (EC) and K. pneumoniae (KP) Harboring NDM-5, P. aeruginosa (PA) Harboring NDM-1 and Candida auris
Authors: Khan Ayesha , Hanson Blake , Dinh An , Wanger Audrey , Ostrosky-Zeichner Luis , Miller William , Arias Cesar
Published: November 2018

Background

The spread of carbapenem resistance in Enterobacteriacae (CRE) and PA is an urgent public health concern. Candida auris (CA) is also an emerging threat, with the epicenter of US cases on the East Coast. Transcontinental spread of multi-drug-resistant (MDR) organisms has the potential to change local susceptibility patterns via dissemination of resistance determinants or high-risk clones. Here, we report and characterize MDR-isolates of EC, KP, PA and CA, all isolated from a single patient admitted to an ICU in Houston, Texas after complications from plastic surgery in India.

Methods

CRE were isolated from the urine, PA from respiratory cultures and CA from wound cultures. Antimicrobial susceptibility testing was performed on Vitek 2 or by Etest. Synergy testing was done by Aztreonam (ATM) E-test on Mueller-Hinton agar supplemented with 2.2 µg/mL avibactam. Bacterial isolates underwent whole genome sequencing on an Illumina MiSeq, and resistance determinants (Abricate using CARD), plasmid replicon types (PlasmidFinder 1.3) and sequence type (Tseemann MLSTtool) were identified. Genes were verified by PCR.

Results

The CRE were resistant to all β-lactams, including ceftazidime/avibactam (CZA) and ceftolozane/tazobactam. Synergy testing with CZA+ATM reduced the ATM MICs of the EC from >256 to 0.5 µg/mL and the KP from >256 to .094 µg/mL, while the PA ATM MIC was 4 µg/mL irrespective of the presence of avibactam. WGS indicated that the EC and KP shared the blaNDM-5, blaTEM-4, and blaCTX-M-15 β-lactamase genes, as well as IncFII and IncX3 plasmid replicon types. In addition, the EC harbored blaCMY-59, blaOXA-181, qnrS1 and two additional IncB and IncY plasmid replicon types. The PA isolate harbored blaNDM-1, qnrVC1, several aminoglycoside resistance genes and a type 1 integrase. The CA isolate had a fluconazole MIC of >256 µg/mL and a micafungin MIC of 0.125 µg/mL.

Conclusion

Here we report the identification of 4 MDR organisms, including the first reported isolate of CA in Houston, in one patient. The pattern of resistance determinants suggests horizontal transmission of blaNDM-5 between the CRE isolates. Prompt recognition of MDR organisms is imperative to prevent healthcare-associated spread.

Disclosures

W. Miller, Merck: Investigator, Research support. C. Arias, Merck & Co., Inc.: Grant Investigator, Research support. MeMed: Grant Investigator, Research support. Allergan: Grant Investigator, Research support.
722. Normal Clinical Signs and Duration of Antibiotics in Hospitalized Patients with Pneumonia
Authors: Ochoa Aileen , Ji Wenjing , Smith Cara , Rhee Chanu , Klompas Michael
Published: November 2018

Background

The most common reason for antibiotic prescribing in hospitalized patients is suspected respiratory tract infection. In many cases, however, antibiotics may be started when the diagnosis is unclear and continued for a fixed course regardless of patients’ clinical trajectories. We sought to characterize the distribution of clinical signs in patients started on antibiotics for possible pneumonia, number of days to normalization of clinical signs, and duration of antibiotics beyond when signs normalized.

Methods

We performed a retrospective analysis on 43,820 consecutive adults admitted to Brigham and Women’s Hospital from May 2017 to January 2018. We identified all nonventilated patients started on antibiotics for pneumonia using clinicians’ stated indications in their medication orders. We analyzed the distribution of clinical signs indicative of pneumonia (maximum temperature, maximum white blood cell count, median respiratory rate, and supplemental oxygen need) on the first day of antibiotics. We then calculated median days to normalization for each sign, total days of antibiotics for pneumonia, and duration of antibiotics beyond when all signs normalized.

Results

We identified 2,754 nonventilated patients started on antibiotics for pneumonia. On the first day of antibiotics, 38%had oxygen saturations ≥95% without supplemental oxygen, 78% had normal temperatures, 63% had normal white blood cell counts, and 79% had median respiratory rates <22 breaths/minute. All signs were normal in 25% of patients. Amongst those with at least one abnormal clinical sign on the first day of antibiotics, all signs returned to normal within a median of 3 days (IQR 2–7 days). Antibiotics were nonetheless continued for ≥3 more days in 33% of these patients.

Conclusion

Pneumonia is a major driver of antibiotic utilization in hospitalized patients but we found 25% of cases lacked the cardinal clinical signs of pneumonia and antibiotics were continued for ≥3 days after all clinical signs normalized in a third of the 75% of patients who did have signs of pneumonia. These findings suggest substantial opportunities to improve antibiotic prescribing for suspected respiratory tract infections in hospitalized patients.

Disclosures

All authors: No reported disclosures.
726. Viral Genomic Load, Cytokine Profiles and Life-Threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants
Authors: Ferolla Fausto Martin , Caratozzolo Ana , Toledano Analía , Anselmino Cecilia , Lobo Carlos Mauricio Vergara , Chiormi Maria Agustina , Visingardi Gabriela , Ratto Patricia , Theiler Graciela , Neira Pablo , Dastugue Mónica , Mascardi Normando , Contrini Maria Marta , Lopez Eduardo
Published: November 2018

Background

Data are controversial regarding the role of viral load and the host immune response in the severity of respiratory syncytial virus (RSV) infection. The objective of this study was t. o analyze the relationship between viral load (VL) and host cytokine responses with RSV life-threatening disease (LTD).

Methods

Prospective cohort study including previously healthy infants <12 months, hospitalized with a first RSV infection in 2017. Viral titers were assessed by qPCR and cytokine levels measured in nasopharyngeal aspirates obtained on admission. All patients with LTD were admitted to the intensive care unit.

Results

Fifty-one patients, median age 3 months (IQR 2–4), 29(56.9%) male. Eight developed LTD (1,569 LTD cases/10,000 RSV-hospitalizations/year [95% CI 702–2.859]). Antibiotic prescription was significantly higher (42.9 vs. 87.5%, P < 0.001) and length of hospitalization significantly prolonged (5.2 ± 1.9 vs. 16.1 ± 12.7 days, P < 0.001) in infants with LTD. No differences were seen in the number of amplification cycles needed for a positive qPCR test (CT) nor in the viral titers of patients with LTD compared with those with better outcome (P = 0.71), Figure 1. VL was not a predictor of LTD (AUC = 0.53); however, no LTD was seen with ≤159,200 copies/mL. CT/VL did not correlate with other outcomes (Figure 2). IFN-y levels (Th1 response) were significantly lower in infants with LTD (P = 0.034). We detected no differences in TNF-α (pro-inflammatory), IL-9, IL-13 (Th2), IL-10 or IL-17 (regulatory) levels from mildly/severely or extremely severe ill patients; lower IL-5 levels were seen in LTD (Figure 3). VL correlated with TNF-α (P < 0.001) and IL-10 (P < 0.001) levels. After logistic regression analysis, socioeconomic, pregnancy and infant variables showed no association with bad outcomes; only frequent consumption of fruits and vegetables during pregnancy conferred protection (aOR 0.03; P < 0.001).

Conclusion

RSV titers did not correlate with LTD. Lower levels of IFN-γ were associated with increased disease severity.

These findings could provide additional data for future RSV preventive and therapeutic strategies.

Disclosures

All authors: No reported disclosures.