bluuebunny/crossref_metadata_2025_split huggingface dataset:
866. Increased Diagnosis of Varicella-Zoster Virus Infection of the Central Nervous System With the BioFire FilmArray Meningitis/Encephalitis Panel
Authors: Chen Lynette , Pettengill Matthew , Hess Bryan , DeSimone Joseph 
Published: November 2018

Abstract

Background
Varicella-zoster virus (VZV) infection of the central nervous system (CNS) is relatively uncommon. Diagnostic tests historically utilized culture, serologies, and targeted PCR methods. In April 2016, our institution began using the BioFire FilmArray meningitis/encephalitis (BFME) panel for cerebrospinal fluid (CSF) specimen analysis. We hypothesized that the diagnosis of VZV CNS infection increased at our institution with the implementation of this diagnostic panel.

Methods
We conducted chart reviews of patients from 2 time periods. In the first period, April 2013–March 2016, BFME was not available for CSF analysis (pre-BFME period). We reviewed all positive CSF VZV PCR results during this period. Medical charts of these patients were reviewed for epidemiology, clinical presentation, treatment course, and outcome. In the second period, April 2016–March 2018, BFME was performed on all CSF specimens obtained by lumbar puncture (BFME period). Patients with a positive VZV result on BFME underwent similar chart review.

Results
In the 3-year pre-BFME period, 292 VZV PCR tests were performed. Six patients were diagnosed with VZV CNS infection; median age 61 years. Five of the 6 patients (83%) had cutaneous zoster. All 6 patients received antiviral therapy. Five of the 6 patients clinically improved; 1 patient with VZV encephalitis died. In the 2-year BFME period, 1,113 CSF samples were evaluated, and 18 of these were positive for VZV (1.6%); median age 55 years. Only 7 of the 18 (39%) had cutaneous zoster at the time of hospitalization. All 18 received antiviral therapy with clinical improvement.

Conclusion
Prior to implementation of the BFME panel at our institution, VZV CNS infection was rarely diagnosed. Diagnosis at that time relied on physicians’ requests for a targeted CSF VZV PCR. The majority of the patients during that period had a concurrent zoster rash. In a shorter period utilizing syndromic testing (BFME) on CSF specimens, we diagnosed 3 times as many cases of VZV CNS disease. Only a minority of these patients presented with a concurrent zoster rash. The use of syndromic testing of CSF will likely identify more cases of VZV CNS disease.

Disclosures
All authors: No reported disclosures.
868. Prospective Pathogen Detection in Patients With Central Nervous System Inflammation Using Metagenomic Sequencing
Authors: Piantadosi Anne , Mukerji Shibani , Ye Simon , Leone Michael , Freimark Lisa , Lemieux Jacob , Solomon Isaac , Ahmed Asim , Kanjilal Sanjat , Goldstein Robert , Ganesh Vijay , Ostrem Bridget , Thon Jesse , Kinsella Cormac , Adams Gordon , Rosenberg Eric , Goldberg Marcia , Sabeti Pardis , Cho Tracey 
Published: November 2018

Abstract

Background
Metagenomic sequencing can identify pathogens in patients with central nervous system (CNS) inflammation, who often have no diagnosis achieved despite extensive clinical testing.

Methods
This prospective study enrolled patients with CNS inflammation at a tertiary hospital from 2016 to 2017. Total nucleic acid was extracted from cerebrospinal fluid (CSF). Libraries were constructed by random primer cDNA synthesis from RNA, and Nextera XT preparation from both cDNA and DNA. Sequencing was performed on an Illumina platform. Reads from human and environmental contaminants were removed. Metagenomic analysis was performed with Kraken and confirmed with viral-ngs. The Institutional Review Board approved the study, and informed consent was obtained.

Results
Of 68 subjects enrolled, 63% were men and 84% were white. The median age was 58 years. The median CSF pleocytosis was 80 cells/mm3 [IQR 17–132]. A median of 2.4 million RNA and 6.8 million DNA sequencing reads were generated per sample. Twenty-five subjects had no diagnosis achieved by routine clinical testing; metagenomic sequencing identified enterovirus in 2 of these subjects, and no pathogen in 23. Thirty-six subjects were clinically diagnosed with an infection. In 12 of these, pathogen nucleic acid was detected in CSF by clinical polymerase chain reaction (PCR); metagenomic sequencing detected the expected pathogen in 10 subjects (83%). The other 24 subjects were clinically diagnosed with infection by serology or PCR from blood. Among these, metagenomic sequencing detected the CSF presence of HIV and locally important tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. Four subjects with West Nile Virus (WNV) infection did not have WNV RNA detected in CSF by sequencing or clinical PCR testing. Among 7 subjects diagnosed with malignancy or autoimmune disease, no pathogens were detected by metagenomic sequencing.

Conclusion
When applied broadly to patients with CNS inflammation, metagenomic sequencing identified known and unexpected pathogens in CSF, including emerging tick-borne pathogens, highlighting its potential as a diagnostic tool. Patients in whom no pathogen nucleic acid was detected could have had an infection with low pathogen burden or short duration in CSF, or a noninfectious syndrome.

Disclosures
All authors: No reported disclosures.
931. Telemedicine for the Treatment of Hepatitis C: A Systematic Review and Meta-Analysis
Authors: De Gijsel David , Kruger Blake , Hakim Dema , Moore Sarah 
Published: November 2018

Abstract

Background
Hepatitis C (HCV) is a curable cause of liver disease, typically treated by specialists. Access to specialists is limited in rural areas. Telemedicine between generalists and specialists could yield outcomes comparable with care provided by specialists in face-to-face (FTF) encounters. To assess the effectiveness of HCV treatment through telemedicine compared with usual care, as measured by sustained virologic response (SVR).

Methods
We searched MEDLINE, the Cochrane Library, ClinicalTrials.gov, the Database of Abstracts of Reviews of Effects, and Excerpta Medica DataBASE from inception to March 2018. We included Randomized Controlled Trials (RCTs) and cohort studies comparing telemedicine in rural settings to FTF encounters with specialists in treating HCV. Studies reported cure as measured by SVR. We did not apply any exclusion criteria. At least 2 independent researchers used PRISMA guidelines to extract data. We used a modified Newcastle-Ottawa Scale and the Cochrane Collaboration Tool for Assessing Risk of Bias to assess observational studies and RCTs. We used a random-effects model to calculate pooled odds ratios (OR). The primary outcome was clinical cure. Cure was defined as SVR at 12 weeks after completion of treatment.

Results
Of 1,211 potentially eligible studies, 10 studies, representing 43,117 subjects, met inclusion criteria. Pooled analysis showed no difference in the odds of achieving SVR when comparing telemedicine to FTF specialist care (OR 1.01 [95% CI 0.78–1.30]). This result was robust across sensitivity analyses, including restriction to patients who completed treatment (OR 0.78 [95% CI 0.43–1.43]), exclusion of outliers, and exclusion of abstracts. There was significant heterogeneity [P = 0.003, I2 = 64].

Conclusion
In rural areas with limited access to specialists, care provided by telemedicine-supported generalists is as effective as FTF specialist care in achieving cure of HCV. Telemedicine is a viable option to expand access to HCV care in rural settings.

Disclosures
All authors: No reported disclosures.
932. Universal Hepatitis C Virus Screening in a Tennessee Tertiary Care Emergency Department
Authors: Chastain Cody A , Johnson Jakea , Miller Karen , Moore Katie , Lako Amanda , Zuckerman Autumn , Han Jin H , Self Wesley H 
Published: November 2018

Abstract

Background
Despite hepatitis C virus (HCV) age cohort and risk factor screening recommendations, many at-risk individuals remain undiagnosed. Current screening practices may not adequately capture those at high risk for infection, especially in regions with increasing injection drug use (IDU). Universal HCV screening in a Tennessee tertiary care emergency department (ED) was introduced to help define regional epidemiology and to improve diagnosis and linkage to care.

Methods
This screening program was implemented in the Vanderbilt University Medical Center ED. Adult patients who underwent phlebotomy for clinical purposes were offered HCV screening. Samples were initially tested for HCV antibodies; if positive, samples were reflexed for HCV RNA testing. Patients with positive HCV RNA tests (i.e., active HCV infection) were notified, counseled, and offered linkage to care.

Results
A total of 11,637 screening tests were performed between April 1, 2017 and March 31, 2018, with 1,008 (8.7%) HCV antibody positive and 488 (4.2%) RNA positive. Of note, 81 (0.7%) were HCV antibody positive but RNA testing could not be performed due to insufficient sample volume. Several notable populations had high rates of HCV (Table 1). Importantly, 3.9% of people not born between 1945 and 1965 were HCV RNA positive, and they were the majority (63.5%) of patients with active HCV (Table 2). A minority (31.6%) of those with active HCV had a known history of IDU (Table 2).

Conclusion
HCV is common among patients presenting for emergency care at a Tennessee tertiary care ED. Universal screening identified many infections that would have been missed using age cohort and risk factors alone. ED HCV screening may be a useful method to augment guideline-based testing and intervene among populations not consistently screened.

Disclosures
C. A. Chastain, Gilead Sciences, Inc.: Grant Investigator and Research Contractor, Grant recipient and Research support. J. Johnson, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. K. Miller, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. J. H. Han, Gilead Sciences, Inc.: Grant Investigator, Grant recipient. W. H. Self, Gilead Sciences, Inc.: Grant Investigator, Grant recipient.
935. Repeat Pregnancies Among Women Living With HIV: Evaluating Temporal Changes in HIV Disease Status and Exploring the Association Between Preterm Birth and Protease Inhibitor Use in Pregnancy
Authors: O’Brien Brigid , Williams Paige , Kacanek Deborah , Chadwick Ellen , Powis Kathleen , Correia Katharine , Haddad Lisa B , Yee Lynn , Chakhtoura Nahida , Dola Chi , Van Dyke Russell B ,   The Pediatric HIV/AIDS Cohort Study
Published: November 2018

Abstract

Background
With improved treatment, women living with HIV (WLHIV) are increasingly becoming pregnant. Studies have shown suboptimal viral suppression following pregnancy. In addition, protease inhibitors (PI) have been associated with preterm birth (PTB).

Methods
We studied WLHIV with at least 2 live births while on the PHACS SMARTT study. We first compared CD4 counts and viral loads (VL) between the first and second pregnancies using Wilcoxon rank-sum tests. We then examined trends in these measures over all reported pregnancies using mixed-effect linear regression models adjusting for maternal age and birth year, with a random effect to account for repeated measures in the same woman over time. Finally, we evaluated the association of PI or non-PI use during pregnancy with PTB, using GEE logistic regression models to adjust for pregnancy number, maternal age, and birth year.

Results
Between 2007 and 2018, 699 women had &gt;1 pregnancy while on study, with a total of 1642 children. Their mean CD4 counts remained stable over repeat pregnancies. Their mean log10 VL decreased between the first and second pregnancies, both early and late in pregnancy (–0.42 cp/mL and –0.16 cp/mL respectively, P &lt; 0.001 for each), but increased by 0.61 cp/mL (P &lt; 0.001) between the end of the first pregnancy and early in the next pregnancy. Most women had VL suppression during pregnancy with VL rebound by the next pregnancy (figure). A majority of women (55%) received a PI in both their first and second pregnancies, with an increase in PTB rate of 4.3%, whereas those who changed from a PI to a non-PI had a decrease of 4.7% (table). Changing to a PI resulted in a stable rate, whereas remaining on a non-PI resulted in a drop of 2%. In adjusted models including all pregnancies, first trimester PI use was associated with an increased rate of PTB (adjusted OR 1.35; 95% CI 1.02, 1.97).

Conclusion
Most WLHIV achieved VL suppression during pregnancy, but many had a VL rebound after pregnancy. First trimester PI use was associated with higher risk of PTB.

Disclosures
E. Chadwick, Abbott Labs: Shareholder, stock dividends. AbbVie: Shareholder, stock dividends. R. B. Van Dyke, Giliad Sciences: Grant Investigator, Research grant.
967. Inhibition of Host Neuraminidase Increases Susceptibility to Invasive Pulmonary Aspergillosis
Authors: Van De Veerdonk Frank , Dewi Intan , Cunha Christina , vanderBeeke Lore , Jaeger Martin , Gresnigt Mark , Resendiz Agustin , Lagrou Katrien , Van De Velde Greetje , Wauters Joost , Carvalho Agostinho 
Published: November 2018

Abstract

Background
Influenza-associated aspergillosis (IAA) is an emerging fungal infection with high mortality and morbidity and the pathogenesis of this disease is not well understood. Interestingly, the number of IAA case reports has increased since the widespread use of neuraminidase inhibitors, such as oseltamivir in 2009. We set out to determine whether oseltamivir could contribute to the pathogenesis of IAA by modulating host responses.

Methods
First, peripheral blood mononuclear cells (PBMCs) and neutrophils from healthy donors were stimulated with neuraminidase (NA)-treated A. fumigatus or were pre-exposed to NA prior to stimulation with Aspergillus conidia. In addition, PBMCs and neutrophils were pretreated with oseltamivir carboxylate prior to stimulation. Cytokines were measured from supernatants after 24 hours of incubation at 37°C. C57BL/6 and BALB/c mice were treated with oseltamivir prior to intranasal challenge with A. fumigatus. Immunosuppression was induced by corticosteroid or cyclophosphamide.

Results
We demonstrate that Aspergillus treated with NA induced an enhanced immune response. Moreover, PBMCs and neutrophils treated with NA produced increased cytokine responses. Blocking NA in vitro with oseltamivir reduced Aspergillus-induced cytokine responses. Next we investigated the effects of blocking neuraminidase activity with oseltamivir in vivo. Immunocompetent mice and mice treated with corticosteroids showed increased mortality, lung fungal burden, and decreased cytokine production when treated with oseltamivir. These effects were not observed in cyclophosphamide-treated mice, suggesting that the effects of NA activity in anti-Aspergillus host defense acts mainly via myeloid cells.

Conclusion
Our results provide evidence that host neuraminidase activity is important for protective anti-Aspergillus immune responses. Treatment with oseltamivir, thus blocking host NA activity, in a setting of corticosteroid use might therefore increase susceptibility to Aspergillus infection. These results warrant further study on the role of neuraminidase and the effects of oseltamivir on susceptibility to invasive pulmonary aspergillosis during active influenza infection.

Disclosures
All authors: No reported disclosures.
970. Emerging Pathogen Candida auris Evades Neutrophil Attack
Authors: Johnson Chad , Davis J Muse , Huttenlocher Anna , Kernien John , Nett Jeniel 
Published: November 2018

Abstract

Background
Candida auris, an emerging fungal pathogen, causes hospital-associated outbreaks of invasive candidiasis with mortality near 60%. Little is known about the pathogenesis of this species that has newly arisen in the last 10 years, and it is unclear why this species is rapidly spreading worldwide. Neutrophils, critical for control of invasive candidiasis, kill fungi through phagocytosis or the release of neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. The objective of this study was to delineate the neutrophil response to C. auris.

Methods
We examined interactions of human neutrophils with C. auris and included C. albicans for comparison. Neutrophil–Candida interactions were visualized by time-lapse fluorescent microscopy and scanning electron microscopy (SEM). We utilized oxidative stress indicator CM-H2DCFDA to measure the generation of reactive oxygen species (ROS) in neutrophils. NET formation was quantified by Sytox Green staining and assessed by SEM and immunofluorescent labeling of NET-associated proteins. Fungal viability was evaluated using microbiological counts and viability stains. We utilized a zebrafish larvae infection model to evaluate neutrophil–Candida interactions in vivo.

Results
Imaging revealed the phagocytosis of C. albicans by human neutrophils followed by the formation of NETs. In contrast, neutrophils encountering C. auris rarely engaged in phagocytosis or produced NETs. By Sytox Green staining, C. auris triggered negligible NET release by human neutrophils, with levels 7-fold lower when compared with C. albicans (Figure A). C. auris did not induce neutrophils to generate ROS, a key signaling mechanism for NET formation. The ineffective neutrophil response to C. auris correlated with diminished fungal killing (Figure B). Imaging of neutrophils in a zebrafish model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to C. auris when compared with C. albicans (Figure C).

Conclusion
C. auris evades neutrophils by altering multiple aspects of their usual anti-candidal responses. We propose that this diminished innate immune response may contribute to the unexpected virulence of C. auris.

Disclosures
All authors: No reported disclosures.
975. Clostridium difficile Infection and Antibiotic Prescription Rates in the Community: Explaining the Gender Gap
Authors: Younas Mariam , Royer Julie , Rac Hana , Justo Julie Ann , Bookstaver P Brandon , Weissman Sharon , Maki Anton , Bell Linda , Waites Katie Stilwell , Dash Sangita , Al-Hasan Majdi N 
Published: November 2018

Abstract

Background
Previous studies have reported higher incidence rates of community-associated Clostridium difficile infection (CA-CDI) in women than in men. This cross-sectional population-based study examines whether this difference in CA-CDI rates across genders is driven by or independent of antibiotic use.

Methods
Medicaid and State Employee Health Plan pharmacy claims for outpatient oral antibiotics and associated medical claims were utilized for estimation of community antibiotic prescription rates in South Carolina population 18 to 64 years of age from January 1, 2015 to December 31, 2015. CA-CDI cases were identified from National Healthcare Safety Network (NHSN) and South Carolina Infectious Disease and Outbreak Network (SCION) through complete enumeration of South Carolina population of the same age and study period as above. Incidence rates of CA-CDI were reported in both men and women 18–39 and 40–64 years of age before and after adjustments for antibiotic prescription rates in the same gender and age group. The 95% confidence intervals (CI) were calculated to examine statistical difference in incidence rates across genders within the same age group.

Results
During the calendar year 2015, a total of 1,564 CA-CDI cases were identified in South Carolina residents 18–64 years of age. The incidence rate of CA-CDI per 100,000 person-years was higher in women than in men in age groups 18–39 years (37.3 [95% CI: 32.8–41.8] vs. 21.0 [95% CI: 17.6–24.4]) and 40–64 years (86.4 [95% CI: 80.1–92.8] vs. 56.6 [95% CI: 51.2–61.9]. Similarly, antibiotic prescription rates per 100 person-years were higher in women than men in the 2 respective age groups (118.8 [95% CI: 118.3–119.3] vs. 54.3 [95% CI: 53.9–54.8] and 130.4 [95% CI: 129.8–130.9] vs. 83.8 [95% CI: 83.3–84.4]. After adjustments for antibiotic prescriptions, there was no significant difference in the incidence rates of CA-CDI per 100,000 prescriptions between women and men 18–39 years of age (31.4 [95% CI: 27.6–35.2] vs. 38.6 [95% CI: 32.4–44.8] and 40–64 years old (66.3 [95% CI 61.5–71.2] vs. 67.5 [95% CI: 61.1–73.8]).

Conclusion
Higher crude incidence rates of CA-CDI in women are likely due to higher outpatient antibiotic prescription rates in women when compared with men.

Disclosures
P. B. Bookstaver, CutisPharma: Scientific Advisor, &lt;$1,000. Melinta Therapeutics: Speaker’s Bureau, &lt;$1,000.
977. An Innovative 3-Year Medical Student Spiral Curriculum in Antimicrobial Stewardship and Infectious Diseases
Authors: Chin-Hong Peter , Teherani Arianne , Irby David , Schwartz Brian 
Published: November 2018

Abstract

Background
By 2050, infections due antimicrobial-resistant organisms are predicted to account for 10 million deaths/year worldwide. Physician antibiotic prescribing patterns are a significant factor in the development of antibiotic resistance organisms. Early, continual, and integrated medical student education may help students develop a framework for responsible antimicrobial use as they develop prescribing patterns.

Methods
We designed a spiral antimicrobial stewardship curriculum (defined as revisiting the same concept but with increasing complexity) for medical students in years 2–4. Data provided by the Graduation Questionnaire (GQ) administered by the US Association of American Colleges were used. We compared student responses during the curriculum rollout in 2013–2015 between students at our institution and other schools. We also surveyed graduating seniors in 2015 about antimicrobial stewardship training.

Results
Using GQ data for the class of 2013 (preintervention), a similar proportion of UCSF medical students compared with other US medical students rated microbiology clinical preparation as excellent (43.6% vs. 45.1%, P &gt; 0.20). For the 2014 class, we developed interactive case-based sessions at the beginning of years 3 and 4. After this first intervention, a higher proportion of UCSF students rated the microbiology clinical preparation as excellent (51.3%) compared with responses at all schools (39.8%, odds ratio [OR] 1.59, 95% confidence interval [CI] 1.1–2.3, P = 0.013). For the class of 2015, we added content during the medicine clerkship and 1 week before graduation. For the 2015 class, an even higher proportion of UCSF students rated microbiology preparation as excellent (57.6%), compared with all schools (41.2%, OR 2.23, 95% CI 1.54–3.22, P &lt; 0.0001). From our survey, 88% were very or extremely satisfied with antimicrobial stewardship training.

Conclusion
A spiral curriculum focusing on antimicrobial stewardship and infectious diseases increases student perception of clinical preparation prior to graduation. As the curriculum was incrementally introduced, students’ knowledge increased indicating a dose–response pattern. Based on these positive results, we plan to introduce more content throughout UME, and link to curriculum for GME and practicing clinicians.

Disclosures
All authors: No reported disclosures.