bluuebunny/crossref_metadata_2025_split huggingface dataset:
415. Airway Gene-Expression Classifiers for Respiratory Syncytial Virus (RSV) Disease Severity in Infants
Authors: Caserta Mary T , Wang Lu , Chu Chin-Yi , Slaunwhite Christopher , Holden-Wiltse Jeanne , Corbett Anthony , Falsey Ann R , Topham David , Mariani Thomas , Walsh Edward E , Qiu Xing 
Published: October 2019

Abstract

Background
RSV infection is common in infants with a majority of those affected displaying mild clinical symptoms. However, a substantial number develop severe symptoms requiring hospitalization. We currently lack sensitive and specific predictors to identify a majority of those who develop severe disease.

Methods
High throughput RNA sequencing (RNAseq) of nasal epithelial cells defined airway gene expression patterns in RSV-infected subjects. Using multivariate linear regression analysis with AIC-based model selection, we built a sparse linear predictor of RSV disease severity, the Nasal Gene Severity Score-NGSS1. Using a similar statistical approach, we built an alternate predictor based upon genes displaying stable expression over time (NGSS2). We evaluated predictive performance of both models using leave-one-out cross-validation analyses.

Results
We defined comprehensive airway gene expression profiles from 106 full-tem previously healthy RSV-infected subjects with a range of RSV disease severity prospectively enrolled in the AsPIRES study. Nasal samples were obtained during acute infection (day 1–10 of illness; 106 samples), and convalescence (day 14–28 of illness; 69 samples). All subjects had a primary infection and were assigned a cumulative clinical illness severity score (GRSS) (Table 1). From the RNA seq data 41 genes were identified as the NGSS1 which is strongly correlated with disease severity (GRSS) in both the naive (ρ=0.935) and cross-validated analysis (ρ of 0.813). As a binary classifier (mild vs. severe), NGSS1 correctly classifies 89.6% of the subjects following cross-validation (Figure 1). Next, we evaluated genes that were stably expressed in both acute illness and convalescence samples in 54 subjects with data from both time points. Repeating the regression based step wise model selection identified 13 genes as NGSS2, which was significantly correlated with GRSS (ρ = 0.741). This model has slightly less, but comparable, prediction accuracy with a cross-validated correlation of 0.741 and cross-validated classification accuracy of 84.0% (Figure 2).

Conclusion
Airway gene expression patterns, obtained following a minimally-invasive nasal procedure, have potential utility as prognostic biomarkers for severe infant RSV infections.

Disclosures
All authors: No reported disclosures.
419. Initial Evaluation of Engagement and Utilization of the National Sexually Transmitted Diseases Curriculum
Authors: Newman Gretchen Snoeyenbos , Unruh Kenton T , Karpenko Andrew Y , Bauer Karin M , Johnston Christine , Workowski Kimberly , Spach David H 
Published: October 2019

Abstract

Background
The National Sexually Transmitted Diseases Curriculum (NSTDC) is an online, guideline-based, interactive curriculum developed at the University of Washington in Seattle with funding from the Centers for Disease Control and Prevention (CDC) National Network of STD Clinical Prevention Training Centers (NNPTC). The NSTDC has dual-functionality to provide users with the option of engaging in (1) sequential, longitudinal learning and/or (2) quick access to specific content. We describe the first evaluation of the reach, utilization and effectiveness of the NSTDC.

Methods
We evaluated user data collected from survey completion, Google Analytics, and the Health Professional Application for Training (HPAT) between the launch of NSTDC in February 1, 2017 through August 31, 2018. Chi-square and ANOVA tests were used to determine significant differences between prescribers, nurses, and non-clinicians.

Results
month period and 54,910 hours of CE awarded. Registered users were mostly women (16,133, 84%), and 8,476 (44%) were registered nurses, with an additional 6,052 (34%) prescribing providers (physicians, nurse practitioners, physician assistants, and dentists). The most common programmatic focus was primary care (4,886, 25%). While 18,175 (95%) of users were in the United States, users were located around the world (Figure 1). Referral patterns differed significantly by occupation (Figure 2). Users engaged deeply with the curriculum. Average site session time was 28 minutes for registered users and 14 minutes for all users. Registered users completed an average of 4.37 out of 7 total modules. Nurses were more likely to complete all modules, (48% vs. 34% of prescribers and 30% of non-clinicians, P < 0.0001). Over 15,000 users answered at least one optional check-on-learning (COL) question. On average, 77% of COL questions were answered in modules where COL questions were initiated. Over 60% of the users found the content and experience highly satisfying. Overall 39% of users intended to change practice following completion of the modules.

Conclusion
The NSTDC has a broad reach, leads to high user engagement and satisfaction, and fosters intent to change practice. This web-based curriculum is a novel and effective strategy to disseminate recommendations from CDC Guidelines.

Disclosures
All authors: No reported disclosures.
424. Use of the ResistancePlus® MG Multiplex PCR Assay to Determine the Prevalence of Mycoplasma genitalium and Macrolide Resistance in a High-Risk US Population
Authors: Cartwright Charles , Harris Ayla , Levandoski Michael , Pherson Amanda , Nye Melinda 
Published: October 2019

Abstract

Background
Mycoplasma genitalium is a significant agent of sexually transmitted infection (STI). Cure rates have declined as rates of macrolide resistance has become increasingly prevalent. Diagnosis of M. genitalium infection and macrolide resistance detection is possible using nucleic-acid amplification tests (NAAT); use of such assays could improve patient management and antimicrobial stewardship. In this study we used one such assay, ResistancePlus MG (RPMG) to determine the prevalence of M. genitalium infection and macrolide resistance in a cohort of patients attending 3 public sexual health clinics in mid-Atlantic US states.

Methods
De-identified urogenital samples submitted to the LabCorp facility in Burlington, NC for routine Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) NAAT testing from 3 public sexual health clinics were analyzed in the study. All samples had been collected in the Aptima Specimen Collection system and tested with the Aptima Combo 2 CT/NG NAAT. A total of 1,261 samples (770 male, 491 female) from this cohort were successfully tested for M. genitalium and macrolide-resistance mediating mutations (MRMM) using the RPMG multiplexed PCR assay.

Results
The prevalence of M. genitalium in this patient cohort was 10.4% (131/1,261), not significantly different to the prevalence of C. trachomatis (12.0%; P = 0.202) but significantly higher than the prevalence of Neisseria gonorrhoeae (6.7%; P = 0.0009). Sixty of the 131 M. genitalium positives were also positive for MRMM and thus azithromycin resistant.

Conclusion
M. genitalium infections were common amongst unselected individuals evaluated for treatable STI in the eastern United States and the rate of macrolide resistance in this population was significant. In addition, the RPMG assay was shown to be a simple and accurate method for simultaneously diagnosing M. genitalium infections and detecting MRMM and could be used to inform therapeutic decisions.

Disclosures
All authors: No reported disclosures.
431. Asymptomatic Latent Syphilis and Stroke in Geriatric Patients; Analysis of Routine Syphilis Tests
Authors: Tago Sayaka , Ishiguri Tomohiro , Hirai Yuji 
Published: October 2019

Abstract

Background
Increasing incidence of syphilis in the young to middle age population is a concern in Japan. Although stroke is a known complication of syphilis, it is unknown for asymptomatic latent syphilis (ALS). Our aim was to investigate the results of routine syphilis tests to find the association between stroke and ALS in geriatric patients.

Methods
This retrospective observational study included patients above 65 years of age who underwent the rapid plasma reagin (RPR) and treponema pallidum hemagglutination assay (TPHA) tests (Showa Medical Science, Kanagawa, Japan) as routine evaluation at an institute from August 2014 to February 2019. Asymptomatic patients with positive TPHA were diagnosed with ALS. Clinical data were collected, including the age, gender, history of stroke, underlying diseases, complications (thoracic aortic aneurysm, aortic regurgitation, dementia), habits, indication for syphilis test, and syphilis description in the medical records. Negative TPHA was the exclusion criterion. A multivariate analysis was used to determine the independent risk factors for stroke. All variables with P < 0.1 in the univariate analysis were evaluated using the multivariate model with the level of significance set at P < 0.05. Statistical analyses were performed using R version 3. 3. 1.

Results
A total of 10,117 geriatric patients underwent the syphilis test in the study period. The TPHA test was positive for 96 patients (0.95%), including 45 (46.9%) men, who were included in the study. The median age was 86 years (range: 65–102). The RPR test was positive for 51 cases (53.1%). The indications for syphilis test were syphilis screening for admission (n = 71), endoscopy (n = 16), health checkup (n = 3), and others (n = 6). No past treatment history for syphilis was found in the medical records. Syphilis descriptions were found for 6 patients (6.25%). One patient had been treated for ALS. A multivariate analysis revealed that positive RPR [odds ratio: 3.39; 95% confidence interval: 1.17 to 9.78; P = 0.0241] was associated with history of stroke.

Conclusion
For ALS in geriatric patients, positive RPR is associated with history of stroke. Medial evaluation about risk for stroke is necessary for ALS in geriatric patients.

Disclosures
All authors: No reported disclosures.
434. Concurrent Gonococcal Infections with Differing Susceptibility Results from the Enhanced Gonococcal Isolate Surveillance Project (eGISP)
Authors: St. Cyr Sancta , Quilter Laura , Pham Cau D , Torrone Elizabeth , Weinstock Hillard 
Published: October 2019

Abstract

Background
Concurrent gonococcal infections could impact treatment success in cases of anatomic site-specific strains with different antimicrobial susceptibilities; however, little is known about same-patient differences in susceptibility as most antibiotic resistance surveillance is based on only male urethral isolates.

Methods
In August 2017, the enhanced Gonococcal Isolate Surveillance Project (eGISP) began collecting male and female genital and extragenital gonococcal isolates from patients in 12 STD clinics. Minimum Inhibitory Concentrations (MICs) for penicillin, tetracycline, ciprofloxacin, gentamicin, cefixime, ceftriaxone and azithromycin were determined by agar dilution. We identified patients with isolates from multiple anatomic sites of infection collected during the same clinic visit. Isolate sets were categorized as pairs or triplets based on the number of culture positive anatomic sites. We identified same-patient isolate sets with differing MICs (≥2 dilution difference) for each antibiotic, and identified if the difference affected susceptibility categorization. All isolates in a set were tested in the same batch run by the same laboratory.

Results
From August 2017-February 2019, 280 isolates were collected from 135 patients, representing 136 isolate sets (128 pairs and 8 triplets); one patient contributed 2 isolate sets. Of the 136 isolate sets, the majority (72; 53%) were grouped as genital and pharyngeal isolates (Table 1). Overall, 33 isolate sets (24%) had differing MICs for ≥1 antibiotic and 21 sets (15%) for ≥2 antibiotics. Across all anatomical site combinations, differing MICs were most common for ciprofloxacin (10.3%), penicillin (9.6%) and azithromycin (9.6%). Only 18 isolate sets (13%) demonstrated differing MICs where an isolate was considered susceptible and another was considered resistant or reduced-susceptible.

Conclusion
Among persons with concurrent gonococcal infections, MICs can vary by ≥2 dilutions between sites and may change susceptibility interpretation. Variation by the anatomic site can result from initial infection with multiple strains or differential development of resistance after infection. Continued surveillance of multi-site infections could help understand resistance development and inform patient management.

Disclosures
All authors: No reported disclosures.
444. Better Efficiency, Same Accuracy: Point-of-Care PCR for the Detection of Group A streptococcus in Noninvasive Skin Infections
Authors: Galdun Patrick D , Close Ryan M , Sutcliffe Catherine , Parker Dennie R , Reid Angelina , McAuley James , Hammitt Laura 
Published: October 2019

Abstract

Background
Group A streptococcus (GAS) is a common cause of skin and soft-tissue infections (SSTIs). Current diagnostic techniques are culture-based and time intensive, requiring the prescription of empiric antibiotics before results are available. New detection tools are needed to hasten the diagnosis and appropriate treatment of SSTIs. The Cobas® Liat® System is a point of care (POC), real-time PCR system developed by Roche Molecular Diagnostics and is used in the United States and Europe to detect GAS from throat swabs within 15 minutes. We evaluated the feasibility and performance characteristics of POC for the detection of GAS in non-severe SSTIs.

Methods
Wound swabs collected from patients presenting to the Whiteriver Indian Health Service Hospital with non-severe SSTIs requiring only outpatient treatment were eligible for inclusion. Two swabs were collected: one swab was cultured on sheep’s blood agar, and the other swab was tested using POC. Compared with culture, we determined the sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) for POC to detect GAS in wound samples. We performed chart reviews 30-days from eligibility to assess the potential impact of POC systems on antibiotic use and healthcare utilization for SSTIs.

Results
To date, we have tested 100 (25%) of our target 400 samples (enrollment will be complete in August 2019). Of the 100 samples, 50 (50%) tested positive for GAS by POC, all of which were culture positive for GAS, 49 tested negative by POC (2 after a first invalid result), all of which tested culture negative for GAS (table), and 1 had an invalid POC result even after repeat testing (culture positive for MRSA only) and was excluded from further analysis. Among samples with a valid POC result, POC SN was 100%, SP was 100%, PPV was 100%, and NPV was 100%. The most common mono-infections were MRSA (22%), GAS (18%), and CoNS (6%). Among GAS cases, MSSA (32%) and MRSA (18%) co-infection was common.

Conclusion
POC PCR is highly sensitive and specific for the detection of GAS in non-severe SSTIs. To our knowledge, this is the first prospective study to use this technology for wound samples. POC PCR methods have the potential to accelerate identification of SSTI pathogens and improve antibiotic prescribing.

Disclosures
All authors: No reported disclosures.
462. Prospective Surveillance of Invasive Group A Streptococcal Infections in Toronto, Ontario, Canada: 1992–2017
Authors: Kandel Christopher , Daneman Nick , Demczuk Walter , Gold Wayne , Green Karen , Martin Irene , Plevneshi Agron , Powis Jeff , Rudnick Wallis , Sarabia Alicia , Schwartz Benjamin , Simor Andrew , Tyrrell Greg , Valiquette Louis , McGeer Allison 
Published: October 2019

Abstract

Background. Background
Invasive Group A streptococcal (iGAS) infections remain a substantial source of morbidity and mortality. We explore the clinical and molecular epidemiology of iGAS infections in Toronto, Ontario, Canada over a 26-year period.

Methods
The Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for iGAS infections in metropolitan Toronto and Peel regions since 1992. Participating microbiology laboratories report and submit sterile site specimens for central processing. M typing was performed on iGAS isolates until September 2006; thereafter emm typing was performed. Clinical information was collected by chart review using standardized collection forms.

Results
Over the 26-year period there were 2819 iGAS infections, representing an average incidence of 2.85 per 100,000 residents with a nadir of 1.65 in 1993 and a peak of 4.52 in 2014. Nosocomial infections occurred in 8.9% (251/2,819). There was substantial variation in annual incidence rates over the study period with increases from 1992 until 2002 and then 2004 until 2014 (analysis for trend, P < 0.001). Skin and soft-tissue infections were the most common clinical presentation, accounting for 33.2% (936/2,819), followed by bacteremia without a focus in 15.4% (435/2,819). Necrotizing fasciitis was observed in 7.4% (208/2,819) and criteria for toxic shock syndrome were met in 17.6% (497/2,819). Overall case fatality within 30 days of hospitalization was 15.3% (95% confidence interval 14.0 to 16.6) and did not change over time. M serotype distribution varied yearly with the most common type being M1 at 22.2% (626/2,189) followed by M12 at 8.2% (230/2,189), then M89 at 5.8% (163/2,189). Antibiotic susceptibility was available from 1998 onwards with overall clindamycin susceptibility at 92.3% (1,957/2,121) and erythromycin susceptibility at 87.9% (1864/2,121).

Conclusion
The incidence of iGAS in Toronto, Ontario has varied over time, with no recent increase apparent. Similar to worldwide observations, M1 serotype was the most commonly isolated; most common serotypes demonstrated cyclical variation. Case fatality rates have remained relatively constant making the development of a vaccine imperative.

Disclosures
All authors: No reported disclosures.
468. Epidemiologic Features of Invasive Methicillin-Resistant Staphylococcus aureus and Group A Streptococcus Infections among Adults Who Inject Drugs in the San Francisco Bay Area, 2008–2017
Authors: Nadle Joelle , Apostol Mirasol , Libby Tanya , Reingold Art 
Published: October 2019

Abstract

Background
Injection drug use has been associated with infection with invasive methicillin-resistant Staphylococcus aureus (iMRSA) and invasive group A Streptococcus (iGAS). In light of the ongoing opioid epidemic, we sought to describe the epidemiologic features of iGAS and iMRSA infections among persons who inject drugs (PWID) in the San Francisco Bay Area.

Methods
Active, population-based surveillance for iMRSA and iGAS was conducted in three California counties during 2008–2017. We defined a case as recovery of MRSA or GAS from a normally sterile site in a surveillance area resident ≥18 years of age. We collected demographic and clinical information and history of injection drug use (IDU) in the past 12 months. Trends in the incidence of infection were assessed using the Cochran-Armitage test for trend. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated comparing PWID and non-PWID.

Results
Of the 6,705 iMRSA and 1,691 iGAS cases identified during 2008–2017, 764 (11%) and 241 (14%), respectively, were among PWID. The proportion of iMRSA cases reporting IDU increased from 9.6% in 2008 to 12.9% (P = 0.017) in 2017 (Figure 1); no significant trend was observed for iGAS cases (Figure 2). Among iMRSA and iGAS cases, PWID cases were younger than non-PWID cases (iMRSA median 46 vs. 63 years, P < 0.0001; iGAS 41 vs. 57 years, P < 0.0001) and were more likely to be homeless (iMRSA OR 8.3, CI 6.7–10.2; iGAS OR 5.4, CI 4.0–7.2), and diagnosed with endocarditis (iMRSA OR 5.9, CI 4.8–7.3; iGAS OR 2.8, CI 1.3–6.4) and internal abscesses (iMRSA OR 4.3, CI 3.5–5.3; iGAS OR 3.4, CI 2.1–5.5) (Table 1). For iMRSA, PWID cases were more likely than non-PWID cases to be community-associated, (OR 2.5, CI 2.1–2.9) and diagnosed with septic arthritis (OR 2.4, CI 1.9–3.0).

Conclusion
The proportion of iMRSA cases reporting IDU significantly increased between 2008 and 2017, in the San Francisco Bay Area. iMRSA and iGAS cases among PWID are younger, more likely to be homeless, and diagnosed with endocarditis and internal abscesses. Prevention measures targeting this younger population who are experiencing homelessness and/or are injecting drugs, may limit severe manifestations of iMRSA and iGAS. These prevention measures should include support of safe injection practices.

Disclosures
All authors: No reported disclosures.
513. Transmission of Carbapenem-Resistant Enterobacteriaceae in a Community-Based, Residential Care Setting: Nevada, 2018
Authors: Gomes Danica , Bardossy Ana , Gorzalski Andrew , Holmstadt Heather , Larson Sandra , Halpin Alison L , Chen Lei , Causey Kimisha , Njoku Chidinma V , Stone Nimalie D , Ogundimu Abimbola , Moulton-Meissner Heather , McAllister Gillian A , Gable Paige , Vlachos Nick , Walters Maroya S , Epstein Lauren , Forero Adrian 
Published: October 2019

Abstract

Background
Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are often multidrug-resistant, and the KPC resistance determinant can be transmitted between bacteria. KPCOs are associated with healthcare facility exposures; identification in community-based, residential care settings is uncommon. In September 2018, the Washoe County Health District was notified of a KPC-producing Escherichia coli from a group home (GH) resident. We investigated the source of this KPCO and evaluated transmission in the GH.

Methods
A case was defined as detection of KPCO from a GH resident or staff from June 1 to November 30, 2018. Staff included caregivers who provided daily care (including toileting, bathing, feeding) and visiting healthcare workers. Residents and staff were offered KPCO screening to assess colonization status. Exposures were assessed by medical record review and interviews. Genetic relatedness of KPCOs was evaluated by whole-genome sequencing (WGS). Infection prevention and control (IPC) practices were reviewed.

Results
Overall, six cases were identified, including the index, two of seven staff screened and three of six residents screened. Three residents with KPCOs had recent hospitalizations and shared a bathroom in the GH; one overlapped on the same hospital unit as a patient with KPC-producing Klebsiella oxytoca. Staff with KPCOs were caregivers who had extensive contact with residents and their environment and no IPC training. Gaps in hand hygiene and environmental cleaning were observed. Organism was recovered from 4 positive screening tests as well as from blood cultures from the index case; all were KPC-producing E. coli. WGS showed that the five E. coli isolates were closely related, consistent with transmission, and harbored the same KPC variant as the K. oxytoca. No new cases occurred after IPC was improved.

Conclusion
A GH resident likely acquired KPCOs during a recent hospitalization, and extensive transmission among GH residents and staff occurred. Factors contributing to transmission included resident dependence on caregivers for daily care and minimal IPC knowledge among caregivers. Facilities with similar populations should increase IPC training to prevent transmission of resistant pathogens.

Disclosures
All authors: No reported disclosures.