bluuebunny/crossref_metadata_2025_split huggingface dataset:
121. Cardiac Implantable Electronic Device-Related Infective Endocarditis (CIED-IE): Clinical Features and Outcomes of Patients with Definite IE Who Fulfill Both Major Duke Criteria
Authors: Gupta Siddhi , Wierzba Thomas F , Peacock James E , Baddour Larry M , Sohail Muhammad R , Le Katherine Y , Vikram Holenarasipur R , Miró José M , Prutkin Jordan M , Greenspon Arnold J , Carrillo Roger , Danik Stephan B , Naber Christoph K , Blank Elisabeth , Tseng Chi-Hong , Uslan Daniel 
Published: October 2019

Abstract

Background
Cardiac implantable electronic device-related infective endocarditis (CIED-IE) comprises 10–57% of total CIED infections. Patients with definite CIED-IE who fulfill both major modified Duke criteria have not been well characterized.

Methods
Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective, multinational study of CIED infections were used to describe a subset of patients with CIED-IE who met both major Duke criteria for definite IE (bloodstream infection and intracardiac vegetations [VEG]).

Results
Of 433 patients with CIED infection, 144 (33.3%) had definite CIED-IE. The median age was 68 years and 77.1% were male. Twelve (8.3%) had past CIED infection. Seventy-seven patients (53.5%) had permanent pacemakers, 38 (26.4%) had implantable cardioverter defibrillators, and 29 (20.1%) had combination devices. The median time following the last device procedure was 550 days. CIED-IE was early in 60 patients (41.7%) and late in 84 (58.3%). Most patients presented with fever (77.8%) and sepsis (44.4%) with a median symptom duration of 7 days. On echocardiography, lead VEG was noted in 125 patients (86.8%) and valvular VEG in 54 patients (37.5%) with the tricuspid valve involved in 56.5%. On the basis of VEG location, there were 90 patients (62.5%) with isolated lead-associated IE (LAE), 19 patients (13.2%) with isolated valve-associated IE (VAE), and 35 patients (24.3%) with both (LVAE). All patients had positive blood cultures and 63/119 (52.9%) had positive lead cultures. The predominant organism in blood was Staphylococcus aureus (42.4%), followed by coagulase-negative staphylococci (20.1%). CIED removal occurred in 131 patients (91%). There were 25 deaths during the index hospitalization and 34 total deaths (24.3%) by 6 months. Mortality correlated with age >75 (P = 0.023) and sepsis on presentation (P = 0.052). Infecting organism, site of VEG, and device removal did not impact the risk of death.

Conclusion
Definite CIED-IE is relatively common. The majority of patients tend to have late-onset infection and often present with sepsis. S. aureus is the dominant organism causing definite CIED-IE. Isolated LAE occurs in 63% of patients. Older age and sepsis on admission are associated with higher mortality.

Disclosures
All authors: No reported disclosures.
2307. Risk factors for Cytomegalovirus (CMV) reactivation and Association with Clinical Outcomes in Critically Ill Adults with Sepsis: A Pooled Analysis of Prospective Studies
Authors: Imlay Hannah , Dasgupta Sayan , Boeckh Michael , Stapleton Renee D , Rubenfeld Gordon D , Chen Ying , Limaye Ajit P 
Published: October 2019

Abstract

Background
CMV reactivation in seropositive, non-immunosuppressed adults with sepsis has been associated with worse clinical outcomes. To inform rational design of interventional trials determining whether CMV prevention improves outcomes, it is critical to identify the independence and strength of the association of CMV reactivation measures with clinically-relevant endpoints. Identification of patient factors associated with CMV reactivation would allow for optimization of the study population.

Methods
We performed a secondary pooled analysis of two prospective cohorts with sepsis: an observational cohort of ICU patients (n = 40) and the placebo cohort from a randomized, double-blind trial of ganciclovir to prevent CMV reactivation in acute critical illness (n = 66). Personnel blinded to the PCR results assessed clinical variables; CMV DNAemia was measured by quantitative plasma PCR twice weekly. Multivariable modeling using logistic and linear methods was used to examine the associations of CMV with clinical outcomes and between baseline patient factors and measures of CMV reactivation (adjusted for age, race, gender, transfusion status, study cohort, and APACHE score).

Results
CMV reactivation occurred at any level in 38/106 (36%), at >100 IU/mL in 25/106 (24%), and at >1,000 IU/mL in 14/106 (13%). In a multivariate model, CMV reactivation at any level, >100 IU/mL, or >1,000 IU/mL was associated with fewer days alive and not requiring ventilation: mean difference of −3.5 days ([95% CI −7.0, 0], P = 0.057), −5.1 days ([−8.9, −1.2], P = 0.012), and −6.1 days ([−10.9, −1.2], P = 0.016), respectively. Multiple measures of CMV reactivation were associated with other clinically-relevant outcomes, even after adjustment for baseline factors (Table 1). The association of APACHE score with CMV reactivation measures was inconsistent and with small effect size. We did not identify other patient variables associated with subsequent CMV reactivation.

Conclusion
CMV reactivation in seropositive adults with sepsis is independently and quantitatively associated with clinically-important outcomes, including death or continued hospitalization by day 28, ventilator-, ICU-, and hospital-free days. These effect sizes provide key data to inform design parameters of future interventional trials.

Disclosures
All authors: No reported disclosures.
2314. Burden of Respiratory Syncytial Virus (RSV) Infection Among Hospitalized Older Adults and Those with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)
Authors: Anderson Evan J , Hussaini Laila , Bristow Laurel , Tippett Ashley , Gibson Theda , Hart Mari , Salazar Luis , Gaffney Michelle , Benyeogor Ifeyinwa Kanayo , Cheng Andrew , Drobeniuc Ana , Traenkner Jessica , Fayad Danielle , Washington Wesley , Emerson Lisa , Schwartz Natalia , Greaves Kandra , Todd Sean , Stanley Corshé , Bechnak Amer , Chaaya Rody Bou , Al-Husien Zayna , Deović Rijalda , Winston Juton , Ahmed Dilshad Rafi , Li Wensheng , Le Khuong , Singh Aditya , Spencer Jennifer E , Muchinsky Amy , Zaks Kathryn , Nesheim Wendy , Stephens Kathy , Swerdlow David L , Hubler Robin , Agosti Yasmeen , Munye Mohamed , Jadhao Samadhan , Ha Binh , McCracken Courtney , Kraft Colleen , Rostad Christina A , Kao Carol , Lopman Ben , Yildirim Inci , Anderson Larry , Rouphael Nadine , Rouphael Nadine 
Published: October 2019

Abstract

Background
Data are limited about the burden of respiratory syncytial virus (RSV)-related hospitalizations in older adults and those with COPD or CHF.

Methods
We conducted prospective surveillance at two hospitals from October 2018 to March 2019 for adults ≥50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region in Atlanta, Georgia. Asymptomatic adults ≥50 years of age were enrolled as controls. Nasopharyngeal and oropharyngeal swabs were tested for RSV and influenza (Flu) using BioFire® FilmArray® Respiratory Viral Panel (RVP) and acute/convalescent serology was obtained for RSV antibodies detection by enzyme immunoassay against RSV lysate. Standard of care results were included for enrollees. We compare the number of RSV+, Flu+ and RSV−/Flu− cases along with demographic features and outcomes.

Results
We screened 12,453 patients to identify 1,515 eligible adults of which 617 (41%) were enrolled. The most common reasons for failing to enroll were refusal (676, 75%) and inability to obtain informed consent (221, 25%). Of the 617, 36 (6%) were RSV+ and 41 (7%) were Flu+. RSV was detected in 1/126 (0.8%) and Flu in 0/126 healthy controls. RSV+ occurred earlier in surveillance and peaked at a higher frequency (figure). Clinical characteristics and outcomes are in the table. In a convenience sample, a four-fold rise in RSV antibody titer was detected among 8/15 RSV+, 0/42 RSV−/Flu−, and 0/42 healthy controls.

Conclusion
The burden and outcomes for RSV are similar to Flu in adults admitted to the hospital with ARI, CHF, or COPD. A vaccine for RSV would be beneficial.

Disclosures
Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.
2315. The Relationship of Pre-Hospital Functional Status and Clinical Outcomes in Patients with Laboratory-Confirmed RSV Infection: Active Population-Based Surveillance, 2017–2019
Authors: Branche Angela , Saiman Lisa , Walsh Edward E , Falsey Ann R , Sieling William , Zachariah Philip , Greendyke William G , Barrett Angela , Vargas Celibell , Alba Luis , Phillips Matthew R , Finelli Lyn 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) infection is a common cause of acute respiratory infection (ARI) in adults. Prospective surveillance enables collection of representative data on demographic and clinical characteristics. Few data of this kind are available for adults hospitalized with RSV infection. We used active population-based surveillance to identify patients with laboratory-confirmed RSV infection and evaluated demographic characteristics and clinical outcomes.

Methods
Hospitalized adults ≥ 18 years old residing in a predefined catchment area with ≥ 2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018–April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. Clinical and demographic data were abstracted from the medical record. Multivariate analysis was used to evaluate the relationship of patient characteristics with clinical outcomes.

Results
8,217 hospitalized adults were screened and 9.4% positive for RSV infection. Preliminary clinical and demographic data were available for 348 patients including 14% 18–49 years, 28% 50–64 years and 58% > 65 years. Mean age was 68 years and 60% were female (Figure 1). Patients had a mean of 3 co-morbidities, with diabetes (40%), chronic obstructive pulmonary disease (30%), chronic kidney disease (28%), congestive heart failure (28%), coronary artery disease (25%) and asthma (24%) the most common co-morbidities (Figure 2). Median hospital length of stay was 6 days (IQR 4–10), 13% of patients were admitted to the ICU, 5% were mechanically ventilated and 5% died during admission and 12% within 6 months. In multivariate analysis having > 3 comorbidities, cardiac disease or a lower baseline functional status measured by activities of daily living scores was significantly associated with 6-month mortality.

Conclusion
The majority of hospitalized patients with RSV infection were older adults with ≥ 3 chronic comorbid conditions. Baseline functional status may be predictive of worse clinical outcomes in patients with RSV infection. These insights into patient characteristics and clinical outcomes will provide information for prevention programs.

Disclosures
All authors: No reported disclosures.
2324. Respiratory Viral Coinfection in a Birth Cohort of Infants in Rural Nepal
Authors: Emanuels Anne , Newman Kira L , Hawes Stephen E , Martin Emily T , Englund Janet A , Tielsch James , Kuypers Jane , Katz Joanne , Khatry Subarna , LeClerq Steven , Chu Helen Y 
Published: October 2019

Abstract

Background
Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the effects of coinfection on disease severity or healthcare seeking are less well-understood.

Methods
A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in rural southern Nepal. Prospective weekly active household-based surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT–PCR. Coinfection was defined as the presence of two or more respiratory viruses simultaneously detected as part of the same illness episode. Maternal vaccination status, infant age, prematurity, and number of children under 5 in the household were adjusted for with multivariate logistic regression.

Results
Of 1,730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected on their primary illness episode. Coinfection status did not differ by maternal vaccination status, infant age, premature birth, and number of children under 5 in the household. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. Overall, infants with coinfection had increased occurrence of fever lasting 4 or more days overall (OR 1.4, 95% CI: 1.1, 2.0), and in the subset of infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 1.0, 1.6).

Conclusion
A high proportion of infants experiencing their first respiratory illness had multiple viruses detected. Coinfection with influenza was associated with longer duration of fever compared with children with influenza alone, but was not associated with increased illness severity by other measures.

Disclosures
All authors: No reported disclosures.
2328. Human Respiratory Syncytial Virus Subgroups among Hospitalized Infants in the United States, 2015–2016
Authors: Rha Brian , Peret Teresa C T , Wang Lijuan , Lively Joana Y , Curns Aaron , Campbell Angela P , Boom Julie A , Azimi Parvin H , Weinberg Geoffrey A , Staat Mary A , Selvarangan Rangaraj , Halasa Natasha B , Englund Janet A , Klein Eileen J , Harrison Christopher J , Stewart Laura S , Szilagyi Peter G , Nayakwadi. Singer Monica , Avadhanula Vasanthi , McNeal Monica , Figueroa-Downing Daniella , Prill Mila M , Whitaker Brett L , Payne Daniel C , Lindstrom Stephen , Thornburg Natalie J , Gerber Susan I , Langley Gayle , Langley Gayle 
Published: October 2019

Abstract

Background
Respiratory syncytial virus (RSV) is a major cause of severe acute respiratory illnesses (ARI) in young children. Circulation of RSV subgroups A and B can vary by season and geographic location, and may have implications for disease susceptibility, outcomes, and prevention measures. We investigated RSV subgroup distribution among samples collected in the New Vaccine Surveillance Network.

Methods
Prospective active surveillance for hospitalized ARI was conducted from November 1, 2015 to June 30, 2016 among children < 12 months of age at seven pediatric hospital sites. Mid-turbinate nasal and throat flocked swabs (combined when both available) and/or tracheal aspirates were collected and tested for RSV at each site using real-time reverse transcription polymerase chain reaction (rRT–PCR) assays; RSV A/B subgroup results were available from four sites that did their own subgroup testing (Cincinnati, Kansas City, Houston, and Oakland). At three sites (Rochester, Nashville, Seattle), approximately 50 RSV-positive specimens were sampled based on the monthly distribution for each site and 1:1 distribution by gender, and then assayed for subgroup at CDC. Patient information was obtained from medical records; chi-square tests were used to compare the distribution of A and B subgroups by site.

Results
Of 704 RSV-positive hospitalized infants, subgroup data from 586 were analyzed; 340 (58%) were RSV A and 246 (42%) were RSV B. The median age for both RSV A and RSV B patients was 2 months. Subgroup distribution varied by geographic location, with the overall proportion of RSV A ranging from 18–83% across sites (P < 0.01). Peak RSV A and B detections by month varied by site, occurring from November–February (figure).

Conclusion
During the 2015–2016 season, RSV A and B subgroups co-circulated among hospitalized infants enrolled at seven US sites. The predominance of RSV subgroup varied by geographic location. Continued surveillance and additional subgroup testing over multiple seasons should improve understanding of the epidemiologic significance of RSV infections by subgroup.

Disclosures
All authors: No reported disclosures.
2340. Diagnostic Stewardship: Survey of Urine Culturing and C. difficile Testing Practices Amongst Oregon Microbiology Labs
Authors: Villamagna Angela H , Cassidy P Maureen , Pierce Rebecca , Tran Dat , Nix Chad , Pfeiffer Christopher 
Published: October 2019

Abstract

Background
Testing for urinary tract infection (UTI) and Clostridiodes difficile infection (CDI) poses diagnostic and antimicrobial stewardship challenges. Both diagnoses hinge on local microbiology laboratory algorithms. For UTI testing, the definition of “abnormal” urinalysis and the use of reflex urine cultures, both of which alter the frequency of bacteriuria detection, likely differs between laboratories. For CDI, pretest probability, choice and sequence of diagnostic tests are likely variable and impact the chances of accurate diagnosis.

Methods
To understand laboratory practices and determine variations in local testing algorithms, we deployed a self-administered survey to microbiology laboratories serving Oregon healthcare facilities via SurveyMonkey in September 2018. Responses were collected through April 2019. We analyzed a subset of questions focused on UTI and CDI diagnosis.

Results
Of 51 surveyed laboratories, response rate was 86% (n = 44). 91% of respondents (n = 40) process bacterial cultures. 47.5% (n = 19) primarily perform urine culture when ordered, whereas the remainder primarily perform cultures in a reflex algorithm when ordered (n = 12; 30%) or a reflex algorithm automatically (n = 9; 22.5%) (Figure 1). The definition of an abnormal urinalysis varied widely (Figure 2). 15% (n = 6) of laboratories reported considering changes to their workflow; two cited a goal of reducing unnecessary testing. Of the 32 laboratories that perform in-house C. difficile testing, the assays and sequence in which they were implemented in testing algorithms varied substantially (Figure 3) and most commonly included NAAT testing. Seven (21.8%) laboratories reported recently changed practices; these changes did not favor any particular algorithm. 84.2% (n = 32) reported stool rejection criteria to limit unnecessary testing, but these criteria varied (Figure 4).

Conclusion
Wide variation exists in laboratory workflows for UTI and CDI diagnoses in Oregon, suggesting lack of consensus on optimal practices. Encouragingly, multiple labs described recently implemented or planned interventions to reduce unnecessary testing for both infections. This snapshot will inform statewide education and interventions to optimize testing and help prevent patient and population harm.

Disclosures
All authors: No reported disclosures.
2358. Understanding the Clinical Implications of Clostridium difficile Detection in the Molecular Age: Colonization vs. Infection in Children Less Than 3 Years of Age
Authors: Hecht Shaina , Wang Huanyu , Everhart Kathy , Watson Joshua , Leber Amy 
Published: October 2019

Abstract

Background
Infants have a high rate of asymptomatic Clostridium difficile (CD) colonization (up to 37%) but can rarely develop true CD infection (CDI). However, currently available polymerase chain reaction (PCR) and enzyme immunoassays (EIA) have suboptimal sensitivity/specificity to distinguish CDI from colonization. Recent data from adults showed that lower cycle threshold (Ct) values of a semi-quantitative CD toxin B gene (tcdB) PCR assay in stool correlated with detection of free CD toxin in stool and poor clinical outcomes. We hypothesized that a tcdB PCR assay may be utilized to distinguish CDI from colonization in patients < 3 years old.

Methods
Symptomatic patients < 3 years old with CD detected by the BioFire FilmArray Gastrointestinal Panel (FGP) were enrolled 2/2018–3/2019. We performed CD tcdB PCR and toxin A/B/GDH EIA on frozen aliquots of stool in Cary Blair. CDI was defined among those that were tcdB PCR positive as (1) a consistent clinical syndrome (diarrhea + no current laxative use), (2) CD EIA toxin+, (3) symptomatic improvement with CDI-directed treatment, and (4) no alternative etiology of diarrhea identified. Patients who did not meet criteria for CDI were considered colonized. We compared median tcdB PCR Ct values between the CDI and colonized groups using the Mann–Whitney test.

Results
Of 193 FGP CD+ patient samples with charts available for review, 37 (19%) samples were EIA GDH+/toxin+, 121 (63%) were GDH+/toxin− and 35 (18%) were EIA−. 150 (78%) samples had detectable tcdB by PCR. Six (4%) patients met criteria for CDI and 144 (96%) for colonization. Median (interquartile range) tcdB PCR Ct values were 23.8 (22.0–29.5) and 30.5 (26.3–35.8) in patients with CDI and colonization, respectively (P = 0.03).

Conclusion
Using a strict clinical and laboratory definition, 4% of evaluable patients < 3 years old met criteria for CDI and had significantly lower tcdB PCR Ct values than colonized patients. A combination of clinical and laboratory criteria, including semi-quantitative tcdB PCR, may help differentiate colonization from CDI in this patient population.

Disclosures
All authors: No reported disclosures.
2359. Prospective Feasibility Study for Novel Ultrasensitive Multiplexed Immunoassay for Clostridiodes difficile Toxins A and B
Authors: Watson Lauren , Zimbric Michele L , Shaughnessy Catherine , Kale Shraddha , Debad Jeff , Navaratnam Manjula , Safdar Nasia 
Published: October 2019

Abstract

Background
The diagnosis of Clostridiodes difficile infection is challenging. A wide array of diagnostic tests are used in practice; however, each available test has important limitations. We examined the feasibility and analytical performance of a novel ultrasensitive multiplexed immunoassay designed by Meso Scale Diagnostics (MSD) compared with five current diagnostic assays for detection of C. difficile toxin A and B.

Methods
Stool, serum and urine samples from 44 admitted inpatients were collected within 72 hours of a standard of care nucleic acid amplification test (NAAT) result (23 positive, 21 negative). These specimens underwent five standard diagnostic assays: enzyme immunoassay for toxins A and B (EIA), cytotoxin cell assay, bacterial culture isolation, and two different NAATs to determine presence of viable C. difficile cells, toxins, and toxin-encoding genes (Table 1). The concentration (fg/mL) of toxin A and toxin B in all stool samples was then quantified using MSD’s multiplexed immunoassay (Table 1).

Results
At least one of the five standard diagnostic tests for C. difficile was positive in 16 of the 23 clinically positive patients. The MSD multiplex immunoassay detected toxin A and/or toxin B in 15 of these 16 samples and quantified low levels of toxin A in one clinically positive sample that was negative for all other tests. In contrast, only 2 of the 16 positive samples were positive by EIA, demonstrating the benefits of the ultrasensitive assay over standard immunoassay methods. All clinically negative specimens were negative in all tests. Toxin detection in urine and serum samples was negligible. In stool samples, the MSD test had an estimated sensitivity of 93% (95% CI: 70–99%) and specificity of 93% (95% CI: 78–98%) compared with the clinically used NAAT.

Conclusion
The MSD multiplex toxin assay is a feasible test to move forward for further evaluation. Ultimately, future studies should examine the performance of this test compared with standard of care in a prospective randomized trial assessing clinical outcomes.

Disclosures
All authors: No reported disclosures.