bluuebunny/crossref_metadata_2025 huggingface dataset:
164. Reporting the High-resolution Structure of the Enterococcal Ribosome: A New Template for Antibiotic Discovery
Authors: Jogl Gerwald , Khayat Reza , Murphy Eileen , Kleffmann Torsten , Singh Kavindra , Murray Barbara , Krause Kurt
Published: November 2018

Background

The ribosome is a rich target for antibiotic design and its structural secrets have been described at the atomic level over the past 2 decades. However, most bacterial ribosome structures come from nonpathogenic species of Archaea or thermophilic bacteria. To aid in the development of modern antibiotics against the enterococcus, we report the structure of the ribosome from Enterococcus faecalis at 3.5 Å resolution using cryo-electron microscopy.

Methods

E. faecalis strain OG1 was grown in liquid culture, collected and lysed using a French press. 70S ribosomes were purified using centrifugation through a sucrose cushion followed by column chromatography and sucrose gradient centrifugation. 70S particles were diluted in buffer and applied to a holey carbon grid and using an FEI vitrobot were flash-frozen in liquid ethane. Data were collected on an FEI Titan Krios operating at 300 kV acceleration voltage. The particles classified into 6 distinct structures based on their composition. Completed maps were utilized for structure modelling using Coot and were then refined using real space refinement within Phenix.

Results

High-quality maps of the 70S ribosome were obtained at up to 3.5 Å resolution in several distinct conformations. The 23S, 16S, and 5S RNA structures were almost completely built into maps with clear density. All but 2 ribosome proteins L25 and L33 have been placed in density. The A, P, and E sites were built into unambiguous density and found to be consistent with other bacterial structures. Notably, 1 EM density map contains an uncharged t-RNA molecule in the E site. The sites identified for current antibiotics are also well defined and interpretable. This 70S structural platform is suitable for structural analysis of antibiotic binding sites, especially for those antibiotics directed specifically against the enterococcal ribosome.

Conclusion

For the first time, the structure of the ribosome from the important human pathogen Enterococcus faecalis has been determined. The maps were obtained at high resolution and found to be suitable for antibiotic design. It is anticipated that the continued determination of the structures of ribosomes from pathogens will aid in the discovery of new treatments for infectious diseases.

Disclosures

All authors: No reported disclosures.
861. Health Disparities in HIV and Pregnancy
Authors: Abbas Anum , Aurit Sarah , Destache Chris , Horne John , Gorby Gary , Vivekanandan Renuga
Published: November 2018

Background

HIV infection in pregnant females confers a higher risk of morbidity and obstetric complications. Widespread use of anti-retroviral therapy (ART) has dramatically decreased vertical HIV transmission. US HIV-infected pregnant females continue to be at higher risk for obstetric complications compared with nonHIV infected females. This study will be conducted with the objective to estimate the current US morbidity and mortality in HIV-infected pregnant females as well as incidence of obstetric complications in this patient population.

Methods

The National Inpatient Sample (NIS) was utilized to identify hospitalizations associated with pregnancy from 2002 to 2014. The aggregation of hospitalizations was stratified into 2 groups based on HIV status to determine whether there were differences in demographic factors, complications, and mortality. All analyses accounted for the NIS sampling design.

Results

There were 39,404,956 pregnancy-related hospitalizations identified; of which, 51,762 were also associated with a positive HIV status. There were differences in complications for those with and without HIV, which included eclampsia (1.27% vs. 0.45%; P < 0.001), preterm labor (11.81% vs. 6.41%; P < 0.001), gestational diabetes (0.92% vs. 0.38%; P < 0.001), group B strep (0.03% vs. <0.01%; P < 0.001), and Gram-negative infection (0.07% vs. 0.03%; P = 0.013). After adjusting for mortality risk, calendar year, age, race and ethnicity, insurance, and zip-code level income, it was found that a positive HIV status was associated with a 91.1% increased odds of mortality (95% CI: 3.9%–351.5%; P = 0.037).

Conclusion

As ART are readily available, we expected better outcomes for our HIV-positive pregnant females. Our results are concerning that there is such an increase rate of mortality and health disparity in HIV-positive pregnant females. As this is a retrospective study, there are limitation and further studies need to be conducted.

Disclosures

All authors: No reported disclosures.
863. Increasing PrEP Uptake: A Diffusion-Based Network Intervention for HIV Prevention Among Young Black Men Who Have Sex With Men
Authors: Ferreira Matthew , Young Lindsay , Schneider John
Published: November 2018

Background

Advances in biomedical prevention strategies provide new opportunities for reducing HIV incidence among young black men who have sex with men (YBMSM). Pre-exposure prophylaxis (PrEP) is for HIV-negative individuals and has been shown to be up to 99% effective in preventing HIV infection when taken as prescribed by CDC clinical practice guidelines. Several studies, however, have documented low rates of PrEP uptake among YBMSM.

Methods

PrEP Chicago is a randomized controlled trial peer leader intervention designed to promote uptake of PrEP for HIV prevention among YBMSM. Participants (n = 423) were recruited using respondent-driven sampling (RDS) and randomized to either an intervention (n = 209) or control (n = 214) condition. Eligibility criteria included: aged 18–35, identifies as a person of color, assigned male sex at birth, had sex with a man in the past 12 months, had an active Facebook profile, and resided in Chicago. The intervention includes a half-day, small group PrEP, and peer leader training workshop followed by monthly check-in booster calls. Approximately 12 months after their initial baseline visit, participants return to complete follow-up data collection and switch conditions, giving year 1 control participants the opportunity to learn about PrEP.

Results

The number of HIV-negative intervention participants on PrEP at baseline vs. 12-month follow-up (PrEP Chicago Study, Chicago, 2016–2018). A total of 341 participants (80.6%) returned at 12 months. Of 209 intervention participants at baseline, 176 (84.2%) completed a follow-up survey at 12 months. At baseline, 13 (13.3%) of 98 HIV-negative intervention participants indicated that they were currently taking PrEP. At 12 months, this number grew to 25 (32.5%) of 77 HIV-negative intervention participants, indicating that they were currently taking PrEP. A total of 21 participants reported initiating PrEP during their time in the intervention.

Conclusion

PrEP is a valuable biomedical intervention for preventing HIV infection in those at risk. PrEP Chicago, a network intervention designed to promote uptake of PrEP among YBMSM, shows promising results for PrEP adoption among this community.

Disclosures

All authors: No reported disclosures.
924. Incidence of Symptomatic and Asymptomatic Influenza Among Healthcare Workers: A Multicenter Prospective Cohort Study
Authors: Bénet Thomas , Valette Martine , Amour Sélilah , Aho-Glélé Serge , Berthelot Philippe , Grando Jacqueline , Landelle Caroline , Lina Bruno , Vanhems Philippe ,   AFP Study Group
Published: November 2018

Background

Influenza is an important cause of viral nosocomial infections; however, the incidence of asymptomatic influenza among healthcare workers (HCWs) is poorly known. The objective was to estimate the cumulative incidence of asymptomatic and symptomatic influenza among HCWs.

Methods

The AFP (Asymptomatic Influenza Project, NCT02868658) multicenter prospective cohort study was conducted in 5 French university hospitals in Lyon (2 sites), Grenoble, Saint-Etienne, and Dijon. Each voluntary HCW was followed-up during the entire 2016–2017 influenza season with 3 visits for influenza diagnostic by PCR from nasal swabs and serology. The outcome was laboratory confirmed influenza (LCI) defined by an influenza detection by PCR, and/or influenza A seroconversion/significant increase in the anti-A antibodies titer against A/Hong-Kong/4801/2014, with the absence of seroconversion/significant increase in the level of anti-B/Brisbane/60/2008 antibodies; influenza A was indeed the only strain circulating this winter in the Lyon area. Asymptomatic cases presented no general or respiratory sign/symptom, paucisymptomatic LCI cases had those symptoms/signs but not conforming to clinical influenza, symptomatic LCI cases had temperature ≥37.8°C and cough or sore throat. Cumulative incidence was expressed per 100 HCWs.

Results

Overall 278 HCWs were analyzed, 84.2% were female, the mean age was 38 years, and influenza vaccination coverage in 2016–2017 was 45.3%. Globally, 62 HCWs had evidence of LCI. Among laboratory confirmed influenza cases, 67.7% (95% CI: 55.8%–79.7%, n = 42) were asymptomatic, 21.0% (95% CI: 10.5%–31.4%, n = 13) were paucisymptomatic, and 11.3% (95% CI: 3.2%–19.4%, n = 7) were symptomatic. Among HCWs, global cumulative influenza incidence was 22.3% (95% CI: 17.7%–27.5%). Cumulative incidence of asymptomatic influenza was 15.1% (95% CI: 10.9%–19.3%), it was 4.7% (95% CI: 2.2%–7.2%) for paucisymptomatic influenza, and 2.5% (95% CI: 0.1%–4.4%) for symptomatic influenza.

Conclusion

Asymptomatic influenza is frequent among HCWs, representing two-third of the influenza burden in this population. This highlights the importance of infection control measures among HCWs no presenting influenza symptoms.

Disclosures

All authors: No reported disclosures.
926. Outbreak of Invasive Nontuberculous Mycobacterium (NTM) Infections Associated With a Pediatric Dental Practice
Authors: Singh Jasjit , O’Donnell Kathleen , Ashouri Negar , Adler-Shohet Felice C , Nieves Delma , Tran M Tuan , Arrieta Antonio , Tran Lisa , Cheung Michele , Zahn Matthew
Published: November 2018

Background

In 2016, an Orange County, California, pediatric dental clinic’s contaminated water system led to the largest outbreak of odontogenic NTM infections yet described.

Methods

Mandatory reporting and active case finding directed by County Public Health were conducted in collaboration with community Pediatric Infectious Disease physicians for patients who underwent pulpotomy at Dental Clinic A from January 1 to September 6, 2016. Confirmed cases were those with positive NTM culture. Probable cases were those with multiple pulmonary nodules on computed tomography (CT), necrotic bone or osteomyelitis seen at surgery, or pathology with positive acid-fast bacilli stain, granulomatous inflammation or chronic osteomyelitis. Clinical data was collected from medical records.

Results

Of 1,089 patients at risk, 71 cases (22 (31%) confirmed and 49 (69%) probable) (Figure 1) had been identified as of March 19, 2018 (Figure 2). Median case age was 6 years (range 2–11 years). Symptoms began a median of 85 days (range 1–409 days) after pulpotomy (Figure 3). Pain and/or swelling on admission were reported in 79%; 21% were asymptomatic. CT findings included 49/70 with abnormalities of the mandible or maxilla, 13/70 with lymphadenopathy, and 19/68 with pulmonary nodules. Only 6/60 had erythrocyte sedimentation rate >40 mm/hour. Of 71 cases, 70 were hospitalized and underwent surgical debridement, for an average of 8.5 inpatient days (range 1–60 days); 23 had >1 hospitalization and 26 required >1 inpatient surgery. Permanent teeth were lost in 45/65 (range of 1–6 teeth lost). Intravenous antibiotics were administered to 32 cases for a median length of 137 days (range 113–282 days). Clofazimine was obtained for 29/32 cases as part of the regimen. Medical therapy was complicated by peripherally inserted central catheter malfunction/replacement/infection (18/27), rash (2/27), neutropenia (12/27), and elevated creatinine (7/27). All treated children showed evidence of jaw healing with resolved or improving lung nodules at 1-year follow-up.

Conclusion

This is the largest outbreak of invasive NTM infections seen associated with a pediatric dental practice. While infections were indolent, patients suffered medical and surgical consequences of treatment. Enhanced national dental water quality standards are needed to prevent future outbreaks.

Disclosures

A. Arrieta, Melinta Therapeutics: Investigator, Research support
930. HCV Treatment Is Associated With a Reduced Risk of Cardiovascular Disease Events: Results From ERCHIVES
Authors: Butt Adeel Ajwad , Yan Peng , Shuaib Ashfaq , Abou-Samra Abdul-Badi , Saikh Obaid , Freiberg Matthew
Published: November 2018

Background

Studies reporting on the association between HCV and cardiovascular disease (CVD), and effect of HCV treatment upon future risk of CVD have shown mixed results.

Methods

Within ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified all persons treated for ≥7 weeks and propensity-score-matched group who never received HCV treatment. We excluded those with HIV, HBV, or previously diagnosed CVD. Incidence rate (per 1,000 person-years) and risk factors for CVD events (Cox proportional hazards analysis) were determined for various treatment groups. CVD events were identified using ICD-9CM/ICD-10 codes. Kaplan–Meier plots were generated to show and compare CVD-free survival by treatment status and attainment of SVR.

Results

Among 32,575 treated and same number of untreated persons in the final dataset, median age was 58 years, 27% were Black race, and 96% were male. The incidence rate for CVD events/1,000 person-years (95% CI) among the treated was 19.10 (17.79, 20.50) vs. 32.37 (30.51, 34.33) among the untreated (P < 0.01). Treatment with a DAA regimen (vs. PEG/RBV; HR [95% CI] 0.68 [0.53,0.88]) and achieving SVR (HR [95% CI] 0.76 [0.63,0.92]) were associated with a lower risk of incidence CVD event (table). Kaplan–Meier curves demonstrated that untreated persons had a shorter CVD event-free survival during 30 months of follow-up compared with the treated persons. (figure; log-rank P < 0.0001)

Conclusion

HCV treatment is associated with a reduction in incident CVD events. Directly acting antiviral regimens (vs. PEG/RBV) and attainment of SVR (vs. no SVR) are associated with a lower risk of incident CVD events.

Disclosures

A. Ajwad Butt, Gilead: Grant Investigator, Research grant.
972. Asymptomatic Carriage of Clostridiodes difficile and Risk of Subsequent Infection
Authors: Espiritu Katrina , Vernon Michael , Schora Donna , Peterson Lance , Singh Kamaljit
Published: November 2018

Background

C. difficile is one of the most common healthcare-associated infections in the United States. Studies of patients with asymptomatic carriage of toxigenic C. difficile have reported conflicting results on the risk of subsequent C. difficile infection (CDI). Older studies suggest that the risk was low and colonization may be protective. Subsequent studies indicate that asymptomatic carriers have a 6-fold greater risk of developing CDI. The aims of our study were to assess the burden of asymptomatic C. difficile carriage and risk of subsequent CDI.

Methods

Adult inpatients at NorthShore University HealthSystem, Illinois hospitals between August 1, 2017 and February 28, 2018 were eligible for the study. Focused admission screening of patients at high risk of C. difficile carriage was performed: (1) history of CDI or colonization, (2) prior hospitalization past 2 months, or (3) admission from a long-term care facility. A rectal swab was collected and tested using the cobas® Cdif Test (Roche) real-time PCR. The development of hospital onset CDI (HO-CDI) in colonized patients was monitored prospectively for at least 2 months. HO-CDI testing of colonized patients was performed using the Cepheid GeneXpert RT-PCR. HO-CDI was defined as patients hospitalized for at least 72 hours with 3 or more episodes of diarrhea/24 hours, in the absence of other potential causes of diarrhea. Patient demographics were collected using a standardized form and data analyzed using VassarStats.

Results

There were 6,104 patients enrolled in the study and 528 (8.7%) were positive on admission for toxigenic C. difficile carriage. The mean age of colonized patients was 75.5 years (range 24–103) and 56.4% (298 patients) were females. Of 528 colonized patients, 21 (4%) had a positive CDI test. A total of 7 patients (1.3%) developed HO-CDI. Mean time to positive HO-CDI was 46.1 days (range 5–120 days). Of 5,576 patients that were negative for C difficile carriage on admission, 14 (0.3%) patients developed HO-CDI. The relative risk of HO-CDI was 5.28 (95% CI: 2.14–13.03, P = 0.05).

Conclusion

We found that 8.7% of at-risk admissions were asymptomatic toxigenic C. difficile carriers. While only 1.3% developed HO-CDI, asymptomatic carriers had a 5 times higher risk of subsequent CDI compared with non-carriers.

Disclosures

All authors: No reported disclosures.
978. Assessing the Impact of a Mobile Device-Based Clinical Decision Support Tool on Guideline Adherence and Mental Workload
Authors: Richardson Katherine , Fouquet Sarah , Kerns Ellen , Mcculloh Russell
Published: November 2018

Background

Fever in infants <90 days old can indicate a serious bacterial infection (SBI) such as urinary tract infection, bacteremia, or meningitis. Clinical management of febrile infants varies widely. Implementing clinical practice guidelines (CPGs) can help standardize care, and electronic clinical decision support (eCDS) tools are a potential means of distributing CPGs. Little is known regarding the individual-level impact of eCDS tool use on medical decision-making. Children’s Mercy Kansas City developed a mobile eCDS tool (CMPeDS: Pediatric Decision Support) that was used internationally in a practice standardization project focused on the management of febrile infants.

Methods

We conducted a prospective cross-over simulation study amongst pediatric healthcare providers. Attending and resident physicians performed simulated patient scenarios using either CMPeDS or a standard text reference (the Harriet Lane Handbook). Participants’ responses in the simulation were evaluated based on adherence to evidence-based guidelines. Participants’ mental workload was assessed using the NASA Task Load Index survey (NASA-TLX, in which lower scores are optimal) to assesses mental, physical, and temporal demand, as well as performance, effort, and frustration when completing a series of tasks. Paired t-test and ANOVA were used to determine significance for case performance scores and NASA-TLX scores, respectively. A System Usability Scale (SUS) was used to determine usability of the CMPeDS app.

Results

A total 28 of 32 planned participants have completed trial procedures to date. Mean performance scores on the cases were significantly higher with CMPeDS vs. standard reference, (87.7% vs. 72.4% [t(27) 3.22, P = 0.003]). Participants reported lower scores on the NASA-TLX when using CMPeDS compared with standard reference tool (Figure 1). Mean score on SUS was 88.2 (scale 0–100) indicating excellent tool usability (Figure 2).

Conclusion

Using the eCDS tool CMPeDS was associated with significantly increased adherence to evidence-based guidelines for febrile infant management and decreased mental workload in simulation. Our findings highlight the potential value of eCDS deployment as part of CPG implementation projects.

Disclosures

All authors: No reported disclosures.
980. Using Videoconferencing with the Clinical Microbiology Lab to Enhance Medical Student Learning During Clinical Rotations
Authors: Chin-Hong Peter , Schwartz Brian
Published: November 2018

Background

Preclinical medical student learning in the microbiology laboratory traditionally focuses on enhancing understanding of microbiology but less on understanding clinical workflow. During a novel course that revisited foundational sciences during clerkships, we designed a virtual microbiology laboratory session to enhance understanding and familiarity with clinical workflow on testing of patient samples.

Methods

The virtual microbiology laboratory sessions were conducted twice in 2018, each including 80 third-year medical students. Clinical cases were used to build upon foundational knowledge. We live-streamed video and audio content from the clinical microbiology laboratory to a remote classroom via the Zoom videoconferencing platform. We conducted the session as a tour and lively interview with microbiology staff who explained the processing as well as diagnostic testing Methods. Students were able to ask questions. To evaluate the sessions we (1) distributed a quantitative survey using a 5-point Likert scale (5 = strongly agree) and (2) conducted focus groups with learners. Qualitative data were analyzed using open and axial coding.

Results

In a questionnaire administered to 160 students, 74% of respondents agreed that the technical aspects and faculty in the session provided the feeling on a “hands-on” tour. Of the respondents, 58% reported that they would be more likely to contact the microbiology laboratory team for help in ordering or interpreting various laboratory tests. In focus groups, learner reflections reinforced the ability of this format to ensure standardization with each student getting to clearly see the demonstration and hear instructor perspectives. Students also appreciated the linear approach of following a specimen from arrival to the laboratory, a better understanding of the laboratory staff and their roles in performing and interpreting laboratory tests. The live feed could be enhanced further by better audio and video synchronization and by reducing ambient noise.

Conclusion

Videoconferencing with the clinical microbiology laboratory can be used to effectively teach microbiology and infectious diseases content to advanced medical students. Whether this exposure to the microbiology laboratory can enhance patient care outcomes requires further study.

Disclosures

All authors: No reported disclosures.
981. A Comprehensive Survey of Infectious Diseases Curriculum Among US Pharmacy Schools
Authors: Jeffres Meghan , Kufel Wesley , Biehle Lauren , Cho Jonathan , Narayanan Navaneeth , Macdougall Conan
Published: November 2018

Background

Pharmacists are key partners in institutional antimicrobial stewardship and require adequate knowledge and skills in antimicrobial pharmacotherapy to fulfill this role, whether or not they have specialized postgraduate training in infectious diseases (ID). The objective of this study was to describe ID topics and teaching strategies across US schools of pharmacy.

Methods

A 23-question electronic survey was sent to ID faculty or curricular deans at all 137 US pharmacy schools.

Results

Surveys were collected from 106 schools (77% response rate). ID curriculum was allotted 60 (IQR 40–80) hours of classroom time and primarily taught in the third year. Respondents dedicated 33% of curriculum hours to ID fundamentals and 66% to disease states. Content was primarily delivered through traditional lectures compared with active learning (75% and 25%, respectively). Greater than 94% of schools taught all tier 1 ID topics from the 2016 American College of Clinical Pharmacy Pharmacotherapy Didactic Curriculum Toolkit. Utilization of active learning methods and time allocated to ID fundamentals differed across schools. Public schools dedicated more time to antimicrobial fundamentals than private schools (40 vs. 30 hours, P = 0.023). Schools using a block schedule allotted more classroom hours to ID content than schools using semester or quarter schedules (77.5 vs. 60 vs. 50 hours, P = 0.001). Schools established less than 5 years ago devoted more classroom hours to active learning than schools established 5 to 10, 11 to 20, and greater than 20 years ago (65 vs. 25 vs. 25 vs. 20, P = 0.012). Private schools were more likely to consistently or frequently use audience response systems (86% vs. 68%, P = 0.037) and concept maps (27% vs. 6%, P = 0.005) compared with public schools. Public schools were more likely to use debates (18% vs. 2%, P = 0.006). Schools established 10 or less years ago were more likely to use concept maps (28% vs. 12%, P = 0.050), games (38% vs. 19%, P = 0.050), and simulation (41% vs. 18%, P = 0.015).

Conclusion

Increased communication and collaboration between ID pharmacotherapy educators is warranted to increase consistency of ID education and distribution of educational innovations.

Disclosures

All authors: No reported disclosures.
1630. Antibiotics Prescribed for Infection Prophylaxis Prior to Dental Procedures Are Frequently Unnecessary in the United States
Authors: Suda Kj , Adimadhyam Sruthi , Calip Greg , Rowan Susan , Gross Alan E , Perez Rose , Hershow Ronald , McGregor Jessina C , Evans Charlesnika
Published: November 2018

Background

Antibiotics are recommended prior to certain dental procedures (“antibiotic prophylaxis”) in patients with select comorbidities to prevent serious distant site infections. Our objective was to assess the appropriateness of antibiotic prophylaxis by dentists using Truven, a national integrated medical, dental, and prescription (Rx) claims database of 350 commercial plans.

Methods

Cross-sectional study of 8.7 million adult dental visits in 2015. Antibiotic prophylaxis was defined as Rx with <3 days supply dispensed within 7 days before a dental visit. Medical diagnoses were evaluated in medical/hospital claims from 2009 to 2015. Patients with hospitalizations and infection diagnoses 14 days prior to the Rx date were excluded. Appropriate antibiotic prophylaxis was defined as a dental visit with a procedure that manipulated the gingiva/tooth periapex in patients with an appropriate cardiac diagnosis. Chi Square and logistic regression were applied.

Results

In 2015, 30,726 antibiotics were prescribed for dental infection prophylaxis for 21,986 patients (mean age=58.6 + 15.0 years; 55.9% female). Amoxicillin (68.5%) and clindamycin (14.7%) were most common. 29,879 dental visits were associated with 69,639 dental codes ([CDTs]; range 1–14 CDTs/visit). Most dental visits were diagnostic (65.9% of visits with >1 diagnostic CDT), preventative (53.0%), and restorative (11.2%). 98.4% of dental visits had an appropriate CDT for antibiotic prophylaxis. Comorbidities include orthopedic implants (45.4%) and cardiac diagnoses at the highest risk of infective endocarditis (22.2%). Per guidelines, 78.0% of dental visits with antibiotic prophylaxis were inappropriate. Amoxicillin was more likely to be inappropriate than other agents (OR=1.65; 95% CI: 1.55–1.76). Orthopedic implants (OR=3.35; 95% CI: 3.14–3.56), tooth implant procedures (OR=3.30; 95% CI: 2.48–4.39), females (OR=1.35; 95% CI: 1.27–1.43) and the western US (OR=1.22; 95% CI: 1.09–1.36) were associated with inappropriate prescribing.

Conclusion

Antibiotic prophylaxis is prescribed for indicated dental procedures, but is not appropriately limited to patients with cardiac diagnoses per guidelines. Implementing antimicrobial stewardship efforts in dental practices may be an opportunity to improve antibiotic prescribing for infection prophylaxis.

Disclosures

J. C. McGregor, Merck: Grant Investigator, Research grant.
1631. Made to Measure: Development of a Scoring Tool to Customize Antimicrobial Stewardship Goals Across a Large Health System
Authors: Logan Andrea Y , Williamson Julie E , Jarrett Steven , Davidson Lisa E
Published: November 2018

Background

The 2015 National Action Plan for Combating Antimicrobial Resistance called for a 20% decrease in antibiotic use among inpatients. Atrium Health (AH), formerly Carolinas HealthCare System, established reductions in antibiotic use (determined by days of therapy [DOT] per 1,000 patient days [PD]) as a yearly system-wide quality goal since 2016. Hospitals in the AH inpatient network vary by size, scope, and antimicrobial stewardship program (ASP) maturity. Prior to our third year, we recognized the need to develop an objective method for determining antibiotic use reduction goals (AURGs); understanding that as ASPs mature, opportunities for reduction stabilize over time and may eventually plateau with consistent ASP. We sought to develop a tool that would better identify hospitals in need of aggressive AURGs.

Methods

A scoring tool was developed to assess ASP implementation and metric achievement at individual hospitals to determine AURGs. Tool components were developed from ASP best practices and consensus among a multi-disciplinary team. The tool yields a maximal score of 41.5 points, with higher scores corresponding to more established ASPs who require less aggressive AURGs. An additional 6 points could be earned for tracked intervention data.

Figure 1. Scoring Tool Components

The tool was applied and a score calculated for each of 27 hospitals. Achieved score placed each hospital into one of 4 AURG ranges: maintain, 1–2.5%, 2.5–5%, and 5–7.5% of DOT/1000 PD. Goals were determined in relation to the median and 75th percentile scores. A minimum score of 39.5, representing full implementation of ASP score components, was required for a maintenance goal.

Results

Scores ranged from 3 to 34.5 points across facilities (median 27.5; 75th percentile 31). Twelve facilities scored below 27.5 points, 10 hospitals between 27.5 and 31 points, and 5 facilities between 31 and 39.5 points corresponding to 5–7.5%, 2.5–5% and 1–2.5% AURGs, respectively.

Figure 2. Facility Scores and AURGs

Conclusion

Scores and corresponding AURGs were generally well accepted by stakeholders at facilities within the AH network. Next steps include examining the feasibility of achieving AURGs and obtaining feedback from facilities to refine the tool. The tool will also be applied to other healthcare networks to assess external validity.

Disclosures

All authors: No reported disclosures.
1635. Do Persons With Opioid Use Disorder and Injection-Related Infections Really Need Prolonged Hospitalizations to Complete Intravenous Antibiotic Therapy?
Authors: Fanucchi Laura , Walsh Sharon , Thornton Alice , Nuzzo Paul , Lofwall Michelle
Published: November 2018

Background

Persons with opioid use disorder (OUD) hospitalized with severe, injection-related infections (e.g., endocarditis) often remain inpatient to complete intravenous (IV) antibiotics due to assumptions that, if outpatient, patients will inject drugs into the IV catheter and will fail to complete prescribed antibiotic regimens. No evidence supports these assumptions, and unfortunately, the inpatient stay infrequently includes OUD pharmacotherapy. The aim is to determine whether inpatients with OUD and injection-related infections can be safely discharged to complete antibiotics through a IV catheter in the context of comprehensive outpatient OUD treatment including buprenorphine.

Methods

Pilot proof-of-concept, randomized study enrolling hospitalized adults with OUD and severe injection-related infections. Participants are provided inpatient buprenorphine treatment with counseling and randomized (1:1) to usual care (UC) [completing IV antibiotics inpatient] or to early discharge (ED) [completing IV antibiotics outpatient]. Both groups receive 12 weeks of comprehensive OUD treatment with buprenorphine after discharge.

Results

Seventy-six patients screened, 20 met eligibility criteria, provided informed consent, and randomized; 10 to UC and 10 to ED. Similar baseline characteristics; 90% in UC with endocarditis and 100% in ED. Length of stay, UC: 45.9 days (SD ±7.8), ED 22.7 (SD ±7.5) (P < 0.001). Ten in UC and 9 in ED completed recommended IV antibiotics, one in ED group is still receiving antibiotics; ED finished 19.8 days (SD ±11.7) IV antibiotics outpatient. Self-reported illicit opioid use 30 days before hospitalization compared with 12-week outpatient phase decreased in both groups (P = 0.009); no significant difference between groups (P = 0.141) (Figure 1).

Conclusion

Early results suggest patients with OUD and complex injection-related infections may be safely discharged to complete IV antibiotics via indwelling catheters if comprehensive OUD treatment with buprenorphine is started while inpatient and continued after discharge. Importantly, while prolonged inpatient care is common practice, viewed as protective but extremely costly, these data suggest that comprehensive outpatient care is feasible and may be equi-effective.

Disclosures

All authors: No reported disclosures.
1642. Safety and Efficacy of Bacteriophage Therapy: Analysis of Clinical Case Series Data
Authors: Aslam Saima , Gilbey Timothy , Maddocks Susan , Morales Sandra , Lehman Susan , Branston Steven , Fabijan Aleksandra Petrovic , Furr Carrie-Lynn Langlais , Rosas Francisco , Bilinsky Igor , Grint Paul , Schooley Robert T , Iredell Jonathan
Published: November 2018

Background

Bacteriophage therapy (BT) is a re-emerging strategy to treat antibiotic-resistant infections. Here, we describe our initial experience with intravenous (IV) and inhaled BT to treat life-threatening Staphylococcus aureus and Pseudomonas aeruginosa infections not responding to antibiotic therapy. Emergency Investigational New Drug application approvals (United States) or Special Access Scheme Category A notifications (Australia) and informed consent from the patients were obtained.

Methods

Patients were treated with AB-SA01 (3-phage product targeting S. aureus) and AB-PA01 (4-phage product targeting P. aeruginosa) produced in a Good Manufacturing Practice-certified facility. Pre- and posttreatment bacterial isolates were tested for phage susceptibility during BT. In all cases, concomitant antibiotics were continued. Safety was assessed clinically and using laboratory parameters with up to 90 days of follow-up. Samples to assess bacterial loads, bacteriophage kinetics in blood, and immune responses to phage were collected.

Results

As of April 2018, 8 patients were treated with BT; 5 with AB-SA01 (bacteremia, n = 4; endocarditis, n = 1) and 3 with AB-PA01 (lung infection, n = 3). Median duration of BT was 14 days and treated patients received over 90 IV doses of AB-SA01 (3 × 109 PFU/dose) and over 490 IV and nebulized doses of AB-PA01 (4 × 109 PFU/dose). BT was well tolerated, with no treatment-related adverse events. Clinical treatment success was documented in 75% of patients. Isolates collected during therapy showed ongoing susceptibility to the BT products with changes in sensitivity to the individual phage components observed in some cases. Bacteriophage kinetics revealed bloodstream clearance within a few hours after IV infusion, with an inferred initial bacteria:bacteriophage ratio of ~200 for the bacteremia patients.

Conclusion

BT was well tolerated as an adjunct to antibiotics, with several examples presented of microbiological eradication and improvement of objective clinical criteria. BT appears to be a safe adjunct to antibiotic therapy in life-threatening S. aureus and P. aeruginosa infections and is a promising candidate for controlled clinical trials.

Disclosures

S. Morales, AmpliPhi Biosciences: Employee, Salary. S. Lehman, AmpliPhi Biosciences: Employee, Salary. S. Branston, AmpliPhi Biosciences: Employee, Salary. A. Petrovic Fabijan, AmpliPhi Biosciences: Collaborator, Research support. C. L. Langlais Furr, AmpliPhi Biosciences: Employee, Salary. F. Rosas, AmpliPhi Biosciences: Employee, Salary. I. Bilinsky, AmpliPhi Biosciences: Employee and Shareholder, Salary. P. Grint, AmpliPhi Biosciences: Board Member, Employee and Shareholder, Salary. J. Iredell, AmpliPhi Biosciences: Collaborator, Research support.
1647. Real-Time Metagenomic Sequencing Reveals Discrete Transmission Clusters Within a Hospital-Associated Norovirus Outbreak
Authors: Casto Amanda , Adler Amanda , Makhsous Negar , Qin Xuan , Crawford Kristen , Jerome Keith , Zerr Danielle , Greninger Alex
Published: November 2018

Background

Norovirus is the most common cause of acute gastroenteritis in the United States and a major challenge for infection control efforts. The high burden of norovirus in most communities and health care systems makes it difficult to discern viral transmission patterns using traditional epidemiological approaches alone.

Methods

We performed real-time metagenomic sequencing of norovirus isolates from an outbreak among inpatients at Seattle Children’s Hospital (SCH). We also sequenced isolates from norovirus cases within the larger University of Washington (UW) Medical System that occurred during and after the outbreak.

Results

Our data showed that the month-long outbreak at SCH was actually characterized by 3 distinct concurrent transmission clusters contained within 3 different hospital units. We were able to report this information to the infection control team at SCH while the outbreak was still in progress. The virus responsible for one of these 3 clusters was genetically stable over a period of 4.5 weeks suggesting serial transmissions from a contaminated fomite, rather than patient to patient transmission. After cases meeting the epidemiological definition for hospital-acquired had ceased, we demonstrated that the virus from one of the 3 outbreak clusters continued to be transmitted to other patients within the SCH medical system. Finally, we showed that one of the patients who acquired norovirus during the outbreak developed a chronic infection with viral shedding documented up until the time of the patient’s death, 8 months after the outbreak.

Conclusion

These results demonstrate the value of using metagenomics as an adjunct to traditional epidemiologic techniques in the setting of a hospital-associated norovirus outbreak. Real-time metagenomic sequencing elucidated viral transmission patterns within the outbreak while it was still in progress and follow-up sequencing revealed further infections due to an outbreak-associated viral strain even after the outbreak was thought to be over. Given this potential, metagenomic analyses represent an invaluable, largely untapped resource for improving our understanding of and reducing adverse effects from viral outbreaks.

Disclosures

All authors: No reported disclosures.
1719. Pharmacokinetics (PK) of Oritavancin in Children: The ORKIDS Trial
Authors: Bradley John , Arrieta Antonio , Bokesch Paula , Fusaro Karen , Griffith David C , Loutit Jeffrey S
Published: November 2018

Background

Oritavancin (ORI) is a lipoglycopeptide antibiotic approved in adults as a single 1,200 mg intravenous (IV) dose for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive organisms, including methicillin-resistant Staphylococcus aureus. The objective in children is to achieve a PK profile that is similar to that attained in adults. PK and safety data from the first 3 age-specified cohorts are presented.

Methods

The ORKIDS trial is a Phase 1 open-label, sequential, dose-finding study evaluating the PK, safety and tolerability of a single-dose 15 mg/kg (max 1,200 mg) IV infusion of oritavancin in children under 18 years. The first 3 age cohorts (12 to <18 years, 6 to <12 years, 2 to < 6 years) with 8 subjects in each cohort have completed the study. Subjects were required to have a suspected or confirmed Gram-positive bacterial infection for which they received standard-of-care antibiotic therapy. Following a single dose of ORI, PK samples were obtained at 3, 4, 9, 24, 48, 72, and 336 hours after the start of the 3-hour infusion. Plasma concentrations were analyzed by noncompartmental Methods. Subjects were evaluated for safety through Day 60. An independent data safety monitoring board evaluated the safety and PK data of each cohort prior to dosing the subsequent cohort.

Results

PK in children compared with adult data from the SOLO Phase 3 ABSSSI studies (Table 1).

Conclusion

In subjects 6 to <18 years, a single 15 mg/kg dose of ORI appears to be well tolerated and provides a PK profile similar to a single 1,200 mg dose in adults. Mean AUC0-inf of 1,963 h μg/mL in subjects 2 to <6 years is lower than the targeted exposure range in adults. A higher dose of ORI is currently being studied in this cohort.

Disclosures

J. Bradley, Melinta Therapeutics: Investigator, Research support. A. Arrieta, Melinta Therapeutics: Investigator, Research support. P. Bokesch, Melinta Therapeutics: Consultant, Consulting fee. K. Fusaro, Melinta Therapeutics: Employee, Salary. D. C. Griffith, Melinta Therapeutics: Consultant, Consulting fee. J. S. Loutit, Melinta Therapeutics: Consultant, Consulting fee.
1720. Regional Differences in Trends of Hospitalizations Associated With Tick-Borne Diseases in the United States, 2009–2014
Authors: Adjemian Jennifer , Lai Yi Ling , Ricotta Emily , Prevots D Rebecca
Published: November 2018

Background

Tick-borne diseases are increasing in incidence in the United States; however, limited data exist on regional trends of associated hospitalizations. Using a nationally distributed dataset of US hospital-based medical records, we aimed to assess trends in incidence of hospitalizations from tick-borne disease by geographic region.

Methods

Data were examined from 156 US hospitals from 2009 to 2014 to identify hospitalizations with tick-borne disease. Cases were described and Poisson regression used to estimate the annual percent change (APC) and associated 95% confidence intervals (CI) in incidence by region over time.

Results

Overall, 2,543 hospitalized patients with tick-borne disease were identified (average annual incidence = 28.4 cases/100,000 hospitalized persons), including 1,613 (63%) with Lyme disease, 379 (15%) tick-borne fever, 293 (12%) ehrlichiosis, 93 (4%) babesiosis, 43 (2%) rickettsiosis, and 122 (4%) multiple tick-related diagnoses. Tick-borne diseases varied significantly by region, with Lyme disease more frequent in those residing in the Northeast (68%) than the South (57%) or West (42%) and tick-borne fever more common in the West (28%) vs. the South (18%), Midwest (14%), and Northeast (13%) (P < 0.0001). Significant increases in tick-borne disease hospitalizations were identified across nearly all US regions, ranging from 15% per year in the South (95% CI=8–24%) to 45% per year in the West (34–58%), with the exception of the Northeast, where incidence declined by 6% per year (0.04–11%). Lyme disease hospitalizations showed similar trends, with the greatest increase in the South (APC = 53%, 95% CI = 33–76%) and a decrease in the Northeast (APC = 13%; 3%–23%). Hospitalizations with tick-borne fever increased in the Midwest (APC = 49%; 8–206%) and Northeast (APC = 18%; 4–34%); with ehrlichiosisincreased in the West (APC = 231%; 75–306%); and with babesiosis increased in the South (APC = 50%; 12–201%) and the Midwest (APC = 21%; 5–39%).

Conclusion

Incidence of hospitalizations from tick-borne disease is increasing throughout much of the nation, except in the Northeast where decreases in Lyme disease were observed. While hospitalizations with tick-borne diseases remain rare, the increases noted are substantial and may reflect rising incidence of these diseases within the represented states.

Disclosures

All authors: No reported disclosures.
1757. Using the Desirability of Outcome Ranking for Management of Antimicrobial Therapy (DOOR-MAT) to Assess Antibiotic Therapy Guided by Rapid Molecular Diagnostics (RMD) in Bloodstream Infection (BSI) Caused by Escherichia coli and Klebsiella pneumoniae
Authors: Wilson Brigid , Viau Roberto , Perez Federico , Jiang Yunyun , Fowler Vance G , Chambers Henry F , Kreiswirth Barry N , Bonomo Robert A , Evans Scott R ,   ARLG
Published: November 2018

Background

In the setting of Escherichia coli and Klebsiella pneumoniae BSI, empiric antibiotic therapy is determined by clinical judgement and Gram stain (GS) of the positive blood culture bottle up to 2 days before antibiotic susceptibility test (AST) results become available. Within hours of GS, RMD can detect E. coli and K. pneumoniae and predict the pattern of susceptibility to β-lactams (BL) of differing spectrum. In this study, our objective was to compare “real-life” empiric therapy for E. coli and K. pneumoniae BSI administered between GS and AST results with simulated RMD-guided therapy.

Methods

We identified a subset of patients hospitalized within VHA between 2006 and 2015 who had a blood culture positive for E. coli or K. pneumoniae, and received empiric BLs between GS and AST Results. We further restricted the cohort to those with observed or implied AST results for 4 representative BLs: cefazolin, ceftriaxone, piperacillin–tazobactam, and imipenem. We extracted BL resistance patterns and, based on previously analyzed RMD performance on 195 E. coli and K. pneumoniae, we simulated RMD results for our cohort by resampling RMD results stratified by resistance pattern at the observed frequencies of resistance patterns in our clinical isolates. We simulated therapy guided by RMDs and compared with the observed empiric BLs using a DOOR-MAT score (Figure 1).

Results

A total of 36,531 BSI cases were identified. Of these, 9,981 E. coli and 4,545 K. pneumoniae met our inclusion criteria (Figure 2). Among these, susceptibility to all BLs occurred in 88% of cases; resistance to all BLs occurred in <0.5%. The isolates previously analyzed using RMD included more resistant phenotypes (Figure 3). Empiric BLs were active in 98% of BSIs, with a mean DOOR-MAT score of 66.1 and 59% of cases classified as “moderate overtreatment.” Simulated RMD-guided BL therapy would be active in 95% of cases with a mean DOOR-MAT score of 91.4 (95% CI, 91.2–91.7), and 7% of cases would be classified as overtreatment.

Conclusion

In a large cohort of BSI patients where rates of BL resistance were low, we observed that empiric BL therapy, although highly effective, is of broader spectrum than necessary. RMD-guided therapy has the potential to reduce overtreatment without compromising effective therapy. DOOR-MAT provides a flexible framework for measuring appropriateness of therapy for BSI.

Disclosures

All authors: No reported disclosures.
1758. Impact of Accelerate Pheno™ Rapid Blood Culture Detection System on Laboratory and Clinical Outcomes in Bacteremic Patients
Authors: Dare Ryan , McCain Kelsey , Lusardi Katherine , Daniels Kay , Painter Jacob , Lakkad Mrinmayee , Emery Nicole , Rosenbaum Eric , Bariola J Ryan
Published: November 2018

Background

Molecular-based automated systems for the rapid diagnosis of bacterial infections have potential to improve patient care. The Accelerate Pheno™ blood culture detection system (ACCEL) is an FDA approved platform that allows for identification (ID) and antimicrobial susceptibility testing (AST) 8 hours following growth in routine culture.

Methods

This is a single-center retrospective chart review of bacteremic adult inpatients before and after implementation of ACCEL. Laboratory and clinical data were collected February–March 2018 (intervention) and compared with a January–April 2017 historical cohort (standard of care). Standard of care ID and AST were performed using VITEK® MS (MALDI-TOF MS) and VITEK®2, respectively. An active antimicrobial stewardship program was in place during both study periods. Patients with polymicrobial cultures, off-panel isolates, previous positive culture, or who were discharged prior to final AST report were excluded. Primary outcome was length of stay (LOS). Secondary outcomes were inpatient antibiotic duration of therapy (DOT) and time to optimal therapy (TTOT). Nonparametric unadjusted analyses were performed due to non-normal distributions. Statistics were performed using SAS 9.4.

Results

Of the 143 positive cultures performed on ACCEL during intervention, 118 (83%) were identified as on-panel organisms. Seventy-five (64%) of these 118 cultures and 79 (70%) of 113 reviewed standard of care cultures met inclusion criteria. Patient comorbidities (P = NS), MEWS severity score (P = 0.10), source of bacteremia (P = NS), and pathogen detected (P = 0.30) were similar between cohorts. Time from collection to ID (28.2 ± 12.7 hours vs. 53.8 ± 20.9 hours; P < 0.001) and AST (31.9 ± 11 hours vs. 71.8 ± 20 hours; P < 0.001) were shorter in the intervention arm.

Conclusion

Compared with standard of care, ACCEL shortens laboratory turn-around-time and improves clinical outcomes. The use of this system has resulted in decreased mean antibiotic DOT, TTOT, and LOS. Further studies are needed to verify these findings.

Disclosures

All authors: No reported disclosures.