bluuebunny/crossref_metadata_2025_split huggingface dataset:
969. GRP78 and Integrin β1/α3 Play Disparate Roles in Epithelium Invasion During Mucormycosis
Authors: Alqarihi Abdullah , Gebremariam Teclegiorgis , Alkhazraji Sondus , Uppuluri Priya , Edwards John E , Ibrahim Ashraf S 
Published: November 2018

Abstract

Background
Mucormycosis is a lethal fungal infection caused by Mucorales. Inhalation is the major route of entry resulting in rhino-orbital or pulmonary infections. Nasal and lung epithelial cells are among the first cells that encounter inhaled spores. We sought to identify the nasal and lung epithelial cell receptors interacting with Rhizopus during tissue invasion.

Methods
R. delemar-induced nasal (CCL30) or lung epithelial (A549) cell invasion was studied using Uvetix dye, while host cell injury was determined by 51Cr-release assay. Epithelial cell receptors were isolated by affinity purification of biotinylated host cell membrane proteins and then identified by LC-MS. Blocking antibodies were used to confirm the role of the receptor in the invasion/injury assays. For survival studies, ICR mice were immunosuppressed with cyclophosphamide and cortisone acetate on day-2, +3, and +8. Mice were infected with 2.5 × 105R. delemar spores intratracheally, and then treated with a single dose of 100 μg (i.p.) anti-β1 integrin antibody. Placebo mice received 100 µg of isotype-matching IgG.

Results
R. delemar invades and damages both cells in a time-dependent manner. Nasal Grp78 and alveolar β1α3 integrin were isolated as putative receptors. Polyclonal antibodies targeting Grp78 or β1 integrin blocked R. delemar-mediated endocytosis of nasal and lung cells by ~70%. Also, anti-Grp78 and anti-β1 integrin antibodies blocked R. delemar-induced nasal and lung cell injury by ~60% (P &lt; 0.001). Elevated glucose, iron, or BHB increased the expression of nasal Grp78 by 2- to 6-fold which resulted in enhanced R. delemar-mediated invasion and injury of host cells, while having no effect on β1α3 integrin expression. Finally, β1 antibodies protected mice from mucormycosis with median survival time of 16 days for treated mice versus 11 days for placebo and an overall survival of 30% versus 0% for placebo mice (P = 0.0006).

Conclusion
The upregulation of Grp78 on nasal epithelial cells in response to physiological elevated concentrations of glucose, iron, and BHB and subsequent enhanced invasion likely to provide insights into why diabetics in ketoacidosis are infected with the rhino-orbital mucormycosis rather than pulmonary disease. Our studies also provide a foundation for therapeutic interventions against mucormycosis.

Disclosures
All authors: No reported disclosures.
982. Summer Outbreak of Severe RSV-B Disease, Minnesota, 2017
Authors: Thielen Beth , Bye Erica , Wang Xiong , Friedlander Hannah , Maroushek Stacene , Shilts Meghan , Strain Anna , Como-Sabetti Kathryn , Ferrieri Patricia , Lynfield Ruth 
Published: November 2018

Abstract

Background
Respiratory syncytial virus (RSV) causes seasonal outbreaks peaking from October to April in the United States. While symptoms are typically mild and limited to the upper respiratory tract in older children and adults, RSV can cause severe lower respiratory disease, hospitalization and death, particularly among younger children, the immunocompromised and the elderly. During summer 2017, the Minnesota Department of Health (MDH) received a report of a cluster of severe respiratory illness in children with RSV-B infection admitted at an urban county hospital.

Methods
MDH conducts surveillance for RSV in Minneapolis-St. Paul with collection of respiratory specimens and clinical and demographic data. We compared characteristics of cases reported in summer 2017 with the previous 4 summer seasons. To understand the genetic relatedness among viruses, we performed complete genome sequencing from primary specimens using an Illumina MiSeq platform employing both a sequence-independent sequencing method and an RSV-specific, overlapping PCR-based approach.

Results
From May to September 2017, 58 cases of RSV (48 RSV-B) were reported to MDH compared with 18 (7 RSV-B) during the same period in 2016, 27 in 2015, and 29 in 2014. The median age and frequency of co-morbidities were similar across years; however, 50% required ICU admission in 2017 compared with 12% in preceding 3 years. The RSV-B genome was sequenced from 10 specimens from March to May 2016, 20 specimens from May to September 2017 and 30 specimens from October 2017-January 2018. Phylogenic analysis revealed that 15 cases from May to September. 2017 formed a unique clade distinct from the lineage encompassing 2016 cases from Minnesota and 35 representative complete RSV genomes in GenBank isolated from 6 continents over 13 years. From October 2017 to January 2018, we detected co-circulation of viruses from both lineages among older adults and children.

Conclusion
We identified an outbreak of RSV-B associated with severe disease among urban Minnesota children during a time of expected low RSV circulation. Complete genome sequencing data suggested emergence of a new lineage distinct from viruses circulating in Minnesota during the previous season. Genomic characterization can provide useful insights into epidemiologic variations.

Disclosures
All authors: No reported disclosures.
1632. Non-Visit-Based and Non-Infection-Related Ambulatory Antibiotic Prescribing
Authors: Linder Jeffrey A , Brown Tiffany , Lee Ji Young , Chua Kao-Ping , Fischer Michael A 
Published: November 2018

Abstract

Background
Many studies have examined or intervened on ambulatory antibiotic prescribing based on infection-related diagnosis codes. However, clinicians may prescribe antibiotics without seeing patients face-to-face or without documenting an infection-related diagnosis.

Methods
We measured the prevalence of non-visit-based and non-infection-related oral, antibacterial–antibiotic prescribing between November 2015 and October 2017 using the EHR of an integrated health delivery system. We examined the visit type (in-person vs. other) and classified prescriptions into 3 mutually exclusive groups based on same-day diagnosis codes: (1) infection-related for prescriptions associated with at least one of 21,730 ICD-10 codes that may signify infection; (2) non-infection-related for prescriptions only associated with the 72,519 ICD-10 codes that do not signify infections; and (3) associated with no diagnosis.

Results
There were 509,534 antibiotic prescriptions made to 279,169 unique patients by 2,413 clinicians in 514 clinics. Patients had a mean age of 43 years old, were 60% women, and 75% white. Clinicians were 54% women; were 63% attending physicians, 18% residents/fellows, 10% nurse practitioners, and 7% physician assistants; and were 41% medical specialists, 21% primary care clinicians, and 7% surgical specialists. The most common antibiotic classes were penicillins (30%), macrolides (23%), cephalosporins (14%), fluoroquinolones (11%), tetracyclines (10%), and sulfonamides (6%). Clinicians prescribed 20% of antibiotics outside of an in-person visit; prescription encounters were in-person (80%), telephone (10%), order-only (4%), refill (4%), and online portal (1%). Clinicians prescribed 46% of antibiotics without an infection-related diagnosis: 54% of antibiotic prescriptions were infection-related, 29% were non-infection-related, and 17% were associated with no diagnosis. Various look-back and look-forward durations for diagnosis codes changed the results only slightly.

Conclusion
Clinicians prescribed 20% of antibiotics outside of in-person visits and 46% of antibiotics without an infection-related diagnosis. Interventions that target visit-based, diagnosis-specific prescriptions miss a large share of antibiotic prescribing.

Disclosures
All authors: No reported disclosures.
1637. Improving Transitions of Care in the Division of Infectious Diseases
Authors: Paim Ana , Vijayvargiya Prakhar , Garrigos Zerelda Esquer , Tan Eugene , O’Horo John 
Published: November 2018

Abstract

Background
Patients dismissed from the hospital on oral or intravenous antibiotics frequently need follow-up appointments with the Division of Infectious Diseases (ID). Follow-up appointments may be inappropriately scheduled with respect to timing and indication. Suboptimal transitions of care may lead to increased no-shows and ultimately poor patient outcomes.

Methods
The baseline sample included 102 patients seen by the inpatient ID services at Mayo Clinic’s Rochester Methodist and Saint Mary’s Hospitals between January 1, 2017 and June 30, 2017. Defects in transitions of care were categorized as those pertaining to sign-off templates, sign-off labels, follow-up priority, and timing. The current transfer of care system from our institution is outlined in Figure 1.

Results
Out of 102 patients, 75 (74%) had at least one defect identified. Root cause analysis revealed multiple factors contributing to this performance gap (Figure 2). Patients often have variable health literacy and social or financial difficulties. There are often multiple ID providers with inadequate time to properly orchestrate follow-up. There are undefined checkpoints and triaging in the department’s scheduling policies. Interventions involved reformatting the ID sign-off template and clarifying the roles of providers in the transitions-of-care process. Analysis after 6 months of implementation revealed improvement of communication among teams, decline in improper sign off by 13% and decrease in antibiotic prescription errors by 2%.

Conclusion
This study demonstrates that well-designed sign-off templates can help with effective communication of the final treatment plan among providers and possibly improve patient outcomes. The target goal is to reduce the number of improper sign-offs by 50% within 1 year.

Disclosures
All authors: No reported disclosures.
1646. Combined Resistance Analyses From Phase 2b Studies of Presatovir Treatment in RSV-Infected Adults
Authors: Porter Danielle , Guo Ying , Perry Jason , Gossage David , Watkins Timothy , Chien Jason , Jordan Robert 
Published: November 2018

Abstract

Background
Presatovir is an oral respiratory syncytial virus (RSV) fusion inhibitor in development for the treatment of RSV infection. Results from a healthy volunteer challenge study show that presatovir significantly reduced RSV viral load and clinical signs and symptoms. Here we present combined resistance analyses from 4 phase 2b studies in naturally RSV-infected adults.

Methods
RSV RNA was isolated from nasal swabs collected at baseline and postbaseline in studies GS-US-218-0108, GS-US-218–1502, GS-US-218–1227, and GS-US-218–1797. Full-length RSV fusion (F) gene was PCR amplified and population sequencing was performed.

Results
Of 233 presatovir-treated adults in the efficacy analyses, post-baseline resistance-associated substitutions were detected in 18 (7.7%) subjects. Frequencies of resistance development varied by study (Table 1). Resistance substitutions known to confer high-level (&gt;200 fold) reduced susceptibility to presatovir detected in &gt;1 subject were: T400I (n = 6), S398L (n = 3), L141F (n = 2), and F140I (n = 2) in F. Subjects with resistant virus had less viral load reduction than presatovir-treated subjects without resistant virus. Resistance development did not impact clinical outcomes. In study GS-US-218-0108, subjects with lymphopenia (&lt;200 cells/μL) at baseline were significantly more likely to develop resistance substitutions.

Conclusion
Presatovir treatment resulted in varying rates of resistance development across 4 phase 2b studies. Resistance development impacted virologic response without affecting clinical outcomes. Differences among study populations and dosing regimens may have influenced rates of resistance development.

Disclosures
D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. Y. Guo, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Perry, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. D. Gossage, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. T. Watkins, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. R. Jordan, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks.
1659. Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Clinical Data and Impact on Hospital Outcome Comparisons
Authors: Rhee Chanu , Jentzsch Maximilian , Kadri Sameer S , Seymour Christopher , Angus Derek , Murphy David , Martin Greg , Dantes Raymund , Epstein Lauren , Fiore Anthony E , Jernigan John A , Danner Robert L , Warren David K , Septimus Edward , Hickok Jason , Poland Russell , Jin Robert , Fram David , Schaaf Richard , Wang Rui , Klompas Michael 
Published: November 2018

Abstract

Background
Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices may confound efforts to benchmark hospital sepsis outcomes using claims data.

Methods
We evaluated the sensitivity of claims data for sepsis and organ dysfunction relative to clinical data from the electronic health records of 193 US hospitals. Sepsis was defined clinically using markers of presumed infection (blood cultures and antibiotic administrations) and concurrent organ dysfunction. Organ dysfunction was measured using laboratory data (acute kidney injury, thrombocytopenia, hepatic injury), vasopressor administrations (shock), or mechanical ventilation (respiratory failure). Correlations between hospitals’ sepsis incidence and mortality rates by claims (using “explicit” ICD-9-CM codes for severe sepsis or septic shock) versus clinical data were measured by the Pearson correlation coefficient (r) and relative hospital rankings using either data source were compared. All estimates were reliability-adjusted to account for random variation using hierarchical logistic regression modeling.

Results
The study cohort included 4.3 million adult hospitalizations in 2013 or 2014. The sensitivity of hospitals’ claims data for sepsis and organ dysfunction was low and variable: median sensitivity 30% (range 5–54%) for sepsis, 66% (range 26–84%) for acute kidney injury, 39% (range 16–60%) for thrombocytopenia, 36% (range 29–44%) for hepatic injury, and 66% (range 29–84%) for shock (Figure 1). There was only moderate correlation between claims and clinical data for hospitals’ sepsis incidence (r = 0.64) and mortality rates (r = 0.61), and relative hospital rankings for sepsis mortality differed substantially using either method (Figure 2). Of 48 (46%) hospitals, 22 ranked in the lowest sepsis mortality quartile by claims shifted to higher mortality quartiles using clinical data.

Conclusion
Variation in the completeness and accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospital sepsis rates and outcomes. Sepsis surveillance using objective clinical data may facilitate more meaningful hospital comparisons.

Disclosures
All authors: No reported disclosures.
1727. Sustained Antimicrobial Activity of a Novel Disinfectant Against Healthcare Pathogens
Authors: Rutala William , Gergen Maria , Sickbert-Bennett Emily , Anderson Deverick J , Weber David 
Published: November 2018

Abstract

Background
Environmental contamination plays an important role in the transmission of MRSA, VRE, and C. difficile. Suboptimal compliance with hand hygiene or inappropriate glove use can result in indirect transfer of these pathogens to patients. This study evaluates a novel disinfectant that claims to kill microbes on surfaces for ≥24 hours.

Methods
We investigated the persistent antimicrobial activity of a novel disinfectant using an EPA protocol for sustained disinfecting activity. In brief, surfaces are inoculated, treated with the novel disinfectant, allowed to dry, and then abraded using a standardized abrasion machine under multiple alternating wet and dry wipe conditions (N = 12) interspersed with 6 re-inoculations. After 24 hours, the surface was re-inoculated a final time and ability of the disinfectant to kill ≥99.9% of 9 test microbes within 5 minutes was measured on 3 test surfaces (glass, formica, and stainless steel).

Results
The novel disinfectant demonstrated a 3–5 log10 reduction in 5 minutes when testing S. aureus, VRE, C. auris, CRE E. coli and antibiotic-sensitive strains of E. coli, and Enterobacter sp. (table). The disinfectant demonstrated lower killing for CRE isolates of Enterobacter sp. and K. pneumoniae, and for antibiotic-sensitive K. pneumoniae (~2 log10 reduction in 5 minutes). When the novel disinfectant was compared with 3 other commonly used disinfectants using the same methodology with S. aureus, the mean log10 reductions were: 4.4 (novel disinfectant); 0.9 (quat-alcohol); 0.2 (improved hydrogen peroxide); and 0.1 (chlorine).

Conclusion
Persistent disinfectants may reduce or eliminate the problem of recontamination and minimize the role of environmental surfaces in transmission of healthcare pathogens.

Disclosures
W. Rutala, PDI: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. D. Weber, PDI: Consultant, Consulting fee
1760. Interferon Gamma Release Assay for Diagnosis of Lyme disease
Authors: Hefter Yosefa , D’Arco Christina , Shute Travis , Dattwyler Raymond , Arnaboldi Paul , Nolan Sheila 
Published: November 2018

Abstract

Background
The sensitivity of current antibody detection assays against Borrelia burgdorferi in the early stage of Lyme disease is very low. In children especially, who commonly have febrile viral illnesses, manifestations of early Lyme disease can be misdiagnosed. We previously demonstrated that IFNγ secretion could be detected in whole blood collected from Lyme disease patients at first clinical presentation following overnight incubation of the blood with peptides derived from B. burgdorferi. In the present study, we further evaluated the utility of IFNγ release for the laboratory diagnosis of Lyme disease in children with varying stages of the illness.

Methods
Children ages 2–18 years with no prior history of Lyme disease and with manifestations of Lyme disease at any stage were enrolled in the study. Sick and healthy controls were enrolled for comparison. We collected history and physical examination data and blood samples at the time of enrollment, at 1 month, and at 6 months. Standard 2-tier testing with ELISA (whole cell sonicate [WCS] and C6) and western blot were run in parallel to the IFNγ release assay for all blood samples. Sensitivity and specificity of the study assay were determined for presentation at all stages of Lyme disease. Clinical data were summarized.

Results
Blood samples from 22 patients with Lyme disease and 7 controls (4 sick, 3 healthy) were obtained at the first visit. The IFNγ release assay detected early and early disseminated Lyme disease with 78% sensitivity compared with 59% sensitivity of 2-tier testing in our study. For patients presenting with a single erythema migrans (EM) lesion, the IFNγ release assay detected Lyme disease with 63% sensitivity compared with 14% sensitivity with 2-tier testing. The IFNγ release assay had only 25% sensitivity for detecting late disease. A single control patient was positive for both the IFNγ release assay and 2-tier serology.

Conclusion
A novel IFNγ release assay demonstrated significantly increased sensitivity when compared with 2-tier testing in the laboratory diagnosis of Lyme disease in patients presenting with a single EM lesion. Future study is needed to determine its utility in detecting early Lyme disease in patients with nonspecific febrile illness in the absence of erythema migrans.

Disclosures
R. Dattwyler, Qiagen: Collaborator, Research support. P. Arnaboldi, Qiagen: Collaborator, research materials.
1761. Effect of Carbapenem-Resistant Enterobacteriaceae (CRE) Surveillance Case Definition Change on CRE Epidemiology—Selected US Sites, 2015–2016
Authors: Duffy Nadezhda , Bulens Sandra N , Reses Hannah , Karlsson Maria S , Ansari Uzma , Bamberg Wendy , Janelle Sarah J , Jacob Jesse T , Bower Chris , Wilson Lucy E , Vaeth Elisabeth , Lynfield Ruth , Witwer Medora , Phipps Erin C , Dumyati Ghinwa , Pierce Rebecca , Cassidy P Maureen , Kainer Marion A , Muleta Daniel , See Isaac 
Published: November 2018

Abstract

Background
Carbapenem-resistant Enterobacteriacae (CRE) are an urgent US public health threat. CDC reported CRE incidence to be 2.93/100,000 population in 2012–2013 in selected sites but changed the CRE surveillance case definition in 2016 to improve sensitivity for detecting carbapenemase-producing (CP) CRE. We describe CRE epidemiology before and after the change.

Methods
Eight CDC Emerging Infections Program sites (CO, GA, MD, MN, NM, NY, OR, TN) conducted active, population-based CRE surveillance in selected counties. A case was defined as having an isolate of E. coli, Enterobacter, or Klebsiella meeting a susceptibility phenotype (figure) at a clinical laboratory from urine or a normally sterile body site in a surveillance area resident in a 30-day period. We collected data from medical records and defined cases as community-associated (CA) if no healthcare risk factors were documented. A convenience sample of isolates were tested for carbapenemase genes at CDC by real-time PCR. We calculated incidence rates (per 100,000 population) by using US Census data. Case epidemiology and the proportion of CP-CRE isolates in 2015 versus 2016 were compared.

Results
In total, 442 incident CRE cases were reported in 2015, and 1,149 cases were reported in 2016. Most isolates were cultured from urine: 87% in 2015 and 92% in 2016 (P &lt; .001). The crude overall pooled mean incidence in 2015 was 2.9 (range by site: 0.45–7.19) and in 2016 was 7.48 (range: 3.13–15.95). The most common CRE genus was Klebsiella (51%) in 2015, and in 2016 was Enterobacter (41%, P &lt; 0.001). Of the subset of CRE isolates tested at CDC, 109/227 (48%) were CP-CRE in 2015 and 109/551 (20%) were CP-CRE in 2016. In 2015, 52/442 (12%) of cases were CA CRE, and in 2016, 267/1,149 (23%) were CA CRE (P &lt; 0.001). In 2016, 3/111 (2.7%) of CA CRE isolates tested were CP-CRE.

Conclusion
A large increase in reported CRE incidence was observed after the change in the case definition. The new case definition includes a substantially larger number of Enterobacter cases. A decrease in CP-CRE prevalence appears to be driven by an increase in non-CP-CRE cases. Although CP-CRE in the community still appear to be rare, a substantial proportion of phenotypic CRE appear to be CA, and CDC is undertaking efforts to further investigate CA CRE, including CP-CRE.

Disclosures
G. Dumyati, Seres: Scientific Advisor, Consulting fee.