bluuebunny/crossref_metadata_2025_split huggingface dataset:
897. Prevalence of Candida auris at Body Sites, Characterization of Skin Microbiota, and Relation of Chlorhexidine Gluconate (CHG) Skin Concentration to C. auris Detection Among Patients at a High-Prevalence Ventilator-Capable Skilled Nursing Facility (vSNF) with Established CHG Bathing
Authors: Hayden Mary K , Dangana Thelma E , Yelin Rachel D , Schoeny Michael , Bell Pamela B , Stanley Mary , Preite Nailliw , Khan Nadia , Edomwande Osayuwamen , Black Stephanie R , Pacilli Massimo , Huang Xin , Deming Clay , Lin Michael Y , Segre Julia A 
Published: October 2019

Abstract

Background
vSNF patients are at high risk of colonization and infection with C. auris. CHG bathing has been used as an intervention to reduce nosocomial transmission of multi-drug-resistant organisms, but its effect on C. auris is unclear.

Methods
We studied a 70-bed ventilator ward in a 300-bed vSNF in Chicago, IL with a high prevalence of C. auris and established CHG bathing. Swab samples were collected from patients for culture, microbiome analysis, and CHG skin concentration testing (Table 1).

Results
We collected 2,467 samples (950 culture, 950 microbiome, 567 CHG) from 57 patients during 2 surveys conducted January–March 2019. Forty-six (81%) patients had C. auris cultured from ≥1 body site. Mean (±SD) age was 59 (±14) years, 40% were women, 70% were African American, mean (±SD) Charlson score was 3 (±2). Patients colonized with C. auris were more likely to be mechanically ventilated (50% vs. 0%, P < 0.001), have a gastrostomy tube (78% vs. 27%, P < 0.001) or have urinary catheter (72% vs. 23%, P = 0.01) than noncolonized patients. Frequency of C. auris isolation varied among 10 body sites tested (P < 0.001); colonization of anterior nares (41%) and hands (40%) was detected most often (Figure 1). By ITS1 analysis, all isolates were members of the C. auris South American clade. Skin microbiome sequencing confirmed culture Results. While Malassezia is the dominant genera observed in healthy volunteers and patients in this vSNF, C. auris was observed to dominate the fungal community of multiple skin sites, including nares, hands, inguinal, toe web (Figure 2). Other Candida spp. were also identified on the skin of patients in the current study, but at lower relative abundance. CHG was detected on skin of 52 (91%) patients (median CHG concentration 19.5 µg/mL; IQR 4.9–78.1 µg/mL). In a mixed-effects model controlling for body site and multiple measurements per patient, odds of C. auris detection by culture were less at CHG concentrations ≥625 µg/mL than at lower concentrations (Figure 3; OR 0.25, 95% CI: 0.10–0.66; P = 0.005).

Conclusion
Frequent C. auris colonization of vSNF patients’ anterior nares and hands suggests that nasal decolonization and patient hand hygiene are potential options to reduce C. auris transmission. High concentrations of CHG may be needed to suppress C. auris on skin.

Disclosures
All Authors: No reported Disclosures.
903. Resensitization to β-Lactams in Enterococci Depends on Penicillin-Binding Protein (PBP) Mislocalization and Is Mediated by a Single Protein That Modulates Cell Membrane (CM) Adaptation to Daptomycin (DAP)
Authors: Khan Ayesha , Nguyen April , Panesso Diana , Vitrac Heidi , Miller William R , Tran Truc T , Shamoo Yousif , Arthur Michel , Arias Cesar A 
Published: October 2019

Abstract

Background
DAP disrupts bacterial CM by binding to septal anionic phospholipids (APLs). LiaX, an effector of the LiaFSR stress system, modulates DAP-R by diverting APLs away from the septum. Enterococci are intrinsically resistant to β-lactams due to the presence of PBPs (e.g., PBP5) with low affinity to these drugs. However, emergence of DAP-R leads to increased susceptibility to β-lactams, a phenomenon designated as the see-saw effect. Here, we dissect the molecular mechanism of this phenomenon.

Methods
We studied a clinical strain pair of DAP-S (S613) and DAP-R (R712) E. faecalis strains recovered from a patient before and after DAP therapy. We generated deletions of liaX and PBPs (ponA and pbp5) in DAP-susceptible (DAP-S) E. faecalis OG1RF and JH2-2. APLs and membrane structures were visualized with NAO and/or FM4-64. PBPs and LiaX localization were evaluated with bocillin-FL or immunofluorescence. PBP transcripts and PBP5 protein levels were measured by qRT-PCR or immunoblotting, respectively. β-Lactam binding affinity of PBPs was assessed by SDS-PAGE of bocillin-FL stained membranes and a LiaX–PBP5 interaction was evaluated by the bacterial two-hybrid (BACTH) system. MICs were determined via E-test.

Results
Deletion of liaX led to DAP-R and redistribution of APL microdomains (nonseptal foci with CM aberrations; Figure 1A) in all strains, with a marked decrease in ceftriaxone (CRO) MICs. Only PBP5 was essential for β-lactam resistance but not for DAP-R. DAP-R was associated with mislocalization of PBPs to the sites of CM aberrations (Figure 2). Notably, LiaX and PBP5 were localized to the septum in DAP-S strains but redistributed away from septal areas upon development of DAP-R (Figure 3). An interaction of LiaX and PBP5 was confirmed by the BACTH system. Mislocalized PBPs, most notably PonA and PBP5, had increased affinity for β-lactams in all DAP-R strains. The increased affinity of PBPs to β-lactams was not associated with increased transcripts or PBP5 levels.

Conclusion
LiaX regulates CM adaptation and cell wall synthesis via membrane remodeling and direct interactions with key PBPs. Changes in LiaX that cause DAP-R results in mislocalization of PBPs to nonseptal areas and likely increases access of β-lactam to the active site, explaining the see-saw effect.

Disclosures
All Authors: No reported Disclosures.
1831. Machine Learning Approaches to Predicting Resistance in Pseudomonas aeruginosa
Authors: Greenberg David E , Kim Jiwoong , Zhan Xiaowei , Shelburne Samuel A , Shelburne Samuel A , Aitken Samuel L , Aitken Samuel L 
Published: October 2019

Abstract

Background
Multi-drug-resistant (MDR) P. aeruginosa (PA) infections continue to cause significant morbidity and mortality in various patient groups including those with malignancies. Predicting antimicrobial resistance (AMR) from whole-genome sequencing data if done rapidly, could aid in providing optimal care to patients.

Methods
To better understand the connections between DNA variation and phenotypic AMR in PA, we developed a new algorithm, variant mapping and prediction of antibiotic resistance (VAMPr), to build association and machine learning prediction models of AMR based on publicly available whole-genome sequencing and antibiotic susceptibility testing (AST) data. A validation cohort of contemporary PA bloodstream isolates was sequenced and AST was performed. Accuracy of predicting AMR for various PA–drug combinations was calculated.

Results
VAMPr was built from 3,393 bacterial isolates (83 PA isolates included) from 9 species that contained AST data for 29 antibiotics. 14,615 variant genotypes were identified within the dataset and 93 association and prediction models were built. 120 PA bloodstream isolates from cancer patients were included for analysis in the validation cohort. ~15% of isolates were carbapenem resistant and ~20% were quinolone resistant. For drug-isolate combinations where >100 isolates were available, machine-learning prediction accuracies ranged from 75.6% (PA and ceftazidime; 90/119 correctly predicted) to 98.1% (PA and amikacin; 105/107 correctly predicted). Machine learning accurately identified known variants that strongly predicted resistance to various antibiotic classes. Examples included specific gyrA mutations (T83I; P < 0.00001) and quinolone resistance.

Conclusion
Machine learning predicted AMR in P. aeruginosa across a number of antibiotics with high accuracy. Given the genomic heterogeneity of PA, increased genomic data for this pathogen will aid in further improving prediction accuracy across all antibiotic classes.

Disclosures
Samuel L. Aitken, PharmD, Melinta Therapeutoics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board
1948. Impact of @WuidQ, a Free Open-access Medical Education Twitter Resource, on Infectious Disease Learning and Teaching
Authors: Escota Gerome V , George Ige , Abdoler Emily 
Published: October 2019

Abstract

Background
Free open-access medical education (FOAMed) is increasingly used as a web-based platform for learning/teaching, with Twitter emerging as a leading medium. However, FOAMed resources in infectious disease (ID) are limited. @WuidQ is the first FOAMed Twitter resource to provide review of ID through board-style, multiple-choice questions (MCQs). We describe its creation and impact to date.

Methods
Two ID faculties created MCQs, vetting them based on accuracy and clarity. MCQs were posted a few times weekly using Twitter’s poll function, with answers tweeted as “threads” linked to the MCQ (Figure 1). We reviewed followers’ profiles to determine their demographics. We also used Twitter metrics to assess participation, including the average number of poll voters, impression (number of tweet views), engagement (number of retweets, clicks), and engagement rate (engagement divided by impression). In order to gauge follower satisfaction, we posted an anonymous online survey that included both close-ended questions utilizing Likert scale and open-ended questions.

Results
Over its first 9 months, @WuidQ reached 1,339 followers (56% based in the United States, 47% healthcare professionals, 13% students/trainees) (Table 1). During this time, it earned 582,400 impressions and had a 3.1% mean engagement rate. We posted 103 MCQs, with a mean of 143 (range 70–316) poll voters per MCQ. Forty-five followers completed the survey; of whom, 49% were ID doctors, 22% were ID fellows, and 11% were medical residents. The vast majority of respondents were between 25 and 44 years of age. Almost all agreed that @WuidQ is engaging and accessible (Figure 2). The majority of respondents who were taking exams agreed that @WuidQ helped them with test preparation. Of those who indicated teaching was a relevant practice, 80% said it helped them teach ID. Lack of time to read and learners’ short attention span were the most common learning barriers addressed by @WuidQ (Figure 4).

Conclusion
@WuidQ is an effective Twitter resource for ID education, filling a gap in FOAMed resources for ID. It has a global reach and caters to learners/teachers across a spectrum of training levels. Given its success, more work is warranted to understand practices for engaging learners and teachers in FOAMed for ID.

Disclosures
All Authors: No reported Disclosures.
1950. Intentional Interprofessional Experiential Education in an HIV/Infectious Diseases Clinic
Authors: Ann Justo Julie , Derrick Caroline , Baliko Beverly , Blake Elizabeth W , Brandon Bookstaver P , Crawford Kimberly , Custer Sabra S , Dunn Brianne L , Grubbs James , Harrison Adrena , Phaup Tricia , Ray Donna D , Reitmeier Melissa C , Sanasi Kamla , Shah Ansal , Ahuja Divya 
Published: October 2019

Abstract

Background
Experiential education opportunities, such as interprofessional practice, are currently limited in HIV care. This intentional interprofessional experiential education (IPEE) offering aimed to improve healthcare student attitudes, perceptions, and skills regarding interprofessional practice and HIV care.

Methods
An interprofessional team of faculty and clinicians designed a 2-week rotation, with each offering consisting of 6–9 students from 4 professions (medicine, nursing, pharmacy, social work). This intentional IPEE was delivered at a single ambulatory care infectious diseases clinic in Columbia, SC. It included time in clinic with providers from varying professions, didactic lectures, a peer health advocate session, and a team capstone project (i.e., simulated, then actual student team visit with an HIV-infected patient, plus note documentation/team presentation). Twelve offerings occurred from October 2016 to February 2019. Anonymous pre- and post-IPEE surveys were provided to each student at baseline and directly after to assess attitudes, perceptions, and skills regarding interprofessional practice and HIV care. Wilcoxon signed-rank tests were used to compare pre- vs. post-survey items. Multivariable logistic regression was used to evaluate predictors for interest in HIV as a specialty.

Results
Of 87 students, 84 (97%) completed both surveys (21 medicine, 25 nursing, 19 pharmacy, 19 social work). Attitudes toward healthcare teams significantly improved in 7/11 items (all P-values ≤ 0.019), teamwork perceptions improved in 5/8 items (P ≤ 0.017), and self-perceived team skills improved in all 6 items (P < 0.001). Students rated provider time in clinic as most valuable (mean 4.6, median 5 on 5-point Likert scale). Following the IPEE, the proportion of students interested in HIV care increased from 53% to 67% (P = 0.07). After adjusting for program year and profession, interest in HIV at baseline was a significant predictor of interest in HIV post-IPEE (aOR 8.2, 95% CI 2.6–25.5).

Conclusion
Short-term, intentional IPEE can positively impact student attitudes, perceptions, and skills regarding interprofessional practice and HIV care. Clinical educators should incorporate intentional HIV IPEE in healthcare curricula.

Disclosures
All Authors: No reported Disclosures.
2846. Perirectal Samples for Analysis of the Gut Microbiota as a Predictive Tool for Multi-drug-Resistant Organism (MDRO) Acquisition in Nursing Facility (NF) Patients
Authors: Wang Joyce , Cassone Marco , Gibson Kristen , Lansing Bonnie , Mody Lona , Snitkin Evan , Rao Krishna 
Published: October 2019

Abstract

Background
Most research examining the association between gut microbiota disruption and MDRO acquisition has been done in acute care settings. Obtaining stool samples in older NF adults is challenging. We hypothesized that perirectal samples can be used as a proxy of the gut microbiota. This prospective cohort study investigated the association between perirectal swab-derived gut microbiota features in newly admitted NF patients and the acquisition of vancomycin-resistant Enterococcus and/or resistant Gram-negative bacteria (rGNB) within 14 days.

Methods
Patients were recruited at 6 MI NFs from September 2016 to October 2018 as part of a larger NIH-funded trial. Colonization status was determined by culture swabs collected from multiple body sites at enrollment, d7, and d14. Our analysis focused on patients with no MDRO at baseline, a perirectal swab collected at baseline, and at least one follow-up visit. The V4 region of the 16S rRNA gene was sequenced from samples and processed with the mothur bioinformatics pipeline. Sequences typically associated with the skin microbiota were removed. The primary outcome was any MDRO acquisition. Exposures of interest included patient and microbiota characteristics. The Microbiome Health Index (MHI) was used to assess microbiota health. An MHI of 0 indicates a balanced abundance between taxa associated with protection and dysbiosis; an MHI above/below 0 suggests better/poorer health, respectively (Figure 1).

Results
Among 60 eligible patients (Table 1), 18 (30%) acquired MDROs within 14 days of enrollment (3 VRE, 13 rGNB, 2 both). The baseline microbiota features differed significantly in those who acquired a new MDRO. Of the major 8 phyla found across samples, patients who acquired an MDRO were depleted in the number of phyla present (4.4 ± 1.1 vs. 5 ± 1.1; P = 0.08) (Figure 2). The log-transformed relative abundance of Enterococcus was enriched in patients who acquired an MDRO (−0.7 ± 3.41) compared with those who did not (−4.2 ± 4.8; P < 0.01) (Figure 3). An MHI below 0 was predictive of MDRO acquisition after adjusting for catheter use within 30 days before baseline (adjusted OR 4.9; 95% CI 1.1–21.1).

Conclusion
Microbiota metrics calculated from perirectal samples are predictive of MDRO acquisition. The clinical utility of perirectal samples warrants further assessment.

Disclosures
All Authors: No reported Disclosures.
2891. Trends in Inpatient Antibiotic Use in US Hospitals, 2012–2017
Authors: Baggs James , Kazakova Sophia , Hatfield Kelly M , Reddy Sujan , Srinivasan Arjun , Hicks Lauri , Neuhauser Melinda M , Jernigan John A 
Published: October 2019

Abstract

Background
The National Action Plan for Combating Antibiotic-resistant Bacteria calls for monitoring inpatient antibiotic use to inform stewardship efforts. We estimated national trends in inpatient antibiotic usage from 2012 to 2017 in a large cohort of US hospitals.

Methods
We utilized the Premier Healthcare Database, containing detailed administrative records available by census region, including inpatient drug utilization data based on billing records, for all patients discharged from a convenience sample of over 700 US hospitals annually, approximately 20% of US inpatient discharges. We retrospectively estimated days of therapy (DOT)/1,000 patient-days (PDs) by year overall and by antibiotic class. To examine trends over time, we created multivariable models adjusting for hospital-specific location of antibiotic use (ICU vs. other) and hospital-specific summary measures including average patient age, average co-morbidity score, case mix index, number of hospital beds, teaching status, urban/rural location, US census division, proportion of discharges with a surgical diagnosis-related code, and proportion of PDs with an infectious disease primary ICD-9/10-CM discharge code. Estimates and models were weighted to be nationally representative using projected weights from the database.

Results
58% of patients had at least one antibiotic DOT, and the overall DOT for all hospitals was 810 DOT/1,000 PDs (interquartile range 701 to 913 DOT/1,000 PDs). Glycopeptides and third-/fourth-generation cephalosporins were the most common antibiotic classes (Figure 1). Overall antibiotic DOT did not change significantly over time, P = 0.9133. However, class-specific DOT varied with large decreases in fluoroquinolones from 2012 to 2017 (55% decrease, P < 0.0001), and large increases in third-/fourth-generation cephalosporins and tetracyclines (32% and 49% increase, respectively, P < 0.0001) (Figure 2). Overall antibiotic DOT significantly varied among US census divisions (Figure 3).

Conclusion
Estimated overall inpatient antibiotic DOT did not change in US hospitals from 2012 to 2017, but there were significant class-specific changes. The large decrease in fluoroquinolone use may reflect increased awareness of adverse events.

Disclosures
All Authors: No reported Disclosures.
2895. Threats to Successful Elimination of Viral Hepatitis: Results from the Nationwide Treatment as Prevention for Hepatitis C (TraP HepC) Program in Iceland
Authors: Gottfredsson Magnus , Runarsdottir Valgerdur , Love Thorvardur J , Fridriksdottir Ragnheidur H , Sigurdardottir Bryndis , Johannsson Birgir , Bjornsson Einar S , Bergmann Ottar M , Love Arthur , Sigmundsdottir Gudrun , Tyrfingsson Thorarinn , Olafsson Sigurdur 
Published: October 2019

Abstract

Background
The main driver of the Hepatitis C virus (HCV) epidemic in most western countries is injection drug use (IDU) among people who inject drugs (PWID). Iceland has provided unrestricted access to direct-acting antiviral agents (DAA) to all HCV-infected patients in the country covered by national health insurance, by a program entitled Treatment as Prevention for Hepatitis C (TraP HepC) from 2016 and is on track to become among the first to achieve the WHO goals of eliminating HCV as a public health threat.

Methods
We analyzed data regarding testing for HCV, incidence of IDU, prevalence of HCV viremia among PWID, drug use in the community and trends in homelessness prior to and during the first 24 months of TraP HepC to monitor outcomes and identify new or persistent challenges.

Results
Intensity of nationwide testing for HCV increased by 22% in 2016, 60% in 2017, and 81% in 2018 compared with previous years (P < 0.001). During 2016–2018 the incidence of new injection drug use, as surveyed among those admitted for addiction treatment increased by 48%. The total number of PWID admitted annually with HCV viremia however remained relatively stable during the entire period (2010–2018). The prevalence of HCV viremia among people recently injecting drugs admitted for addiction treatment however dropped from 48.7% to 16.2% in 2017, and to 10.2% in 2018 (P < 0.001). Analysis of data regarding stimulant use, as measured by drug levels in wastewater shows an almost threefold increase of amphetamine and an eightfold increase in cocaine levels during 2016–2018 compared with 2015. Concurrently, the number of homeless has doubled. Two years into TraP HepC > 80% of the estimated total HCV-infected population were started on their first course of DAAs. By intention to treat analysis, the cure rate was 92.4% among patients without history of IDU in the past 6 months, compared with 82.9% among active IDU (P = 0.0006); those with history of recent IDU were more likely to discontinue (P < 0.0001). Homelessness carried the highest relative risk (RR) of treatment failure (RR = 2.4, P = 0.008), mostly due to discontinuation.

Conclusion
Iceland is on track to eliminate HCV, but challenges such as increasing drug use in the community and homelessness need to continuously monitored and addressed; they may jeopardize the success of elimination efforts.

Disclosures
All Authors: No reported Disclosures.
2901. Measles in the United States During the Postelimination Era, 2017–2019
Authors: Gastanaduy Paul , Lee Adria D , Redd Susan B , Clemmons Nakia S , Patel Manisha , Patel Manisha 
Published: October 2019

Abstract

Background
Measles, a vaccine-preventable viral illness that can cause serious complications, was declared eliminated from the United States in 2000 because of a successful measles vaccination program. Recent years have seen an increase in the number of measles cases and outbreaks. We summarized measles epidemiology in the United States during 2017–2019.

Methods
We reviewed US national surveillance data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2017–April 26, 2019. We describe the demographic characteristics, vaccination status, and disease epidemiology of measles cases.

Results
During 2017–April 2019, 1,196 measles cases were reported in 37 US States and Washington DC, including 146 (12%) importations from 37 countries; 108 (74%) of importations were US residents returning from travel abroad, of which 60 (56%) were unvaccinated and 31 (29%) had unknown vaccinations status. Among 1,148 cases who were US-residents, the highest incidence of measles was among infants and children aged 6–11 and 12–15 months (112 cases [19 cases/million person-years] and 106 cases [27 cases/million person-years], respectively). Among US-resident cases, 846 (74%) were unvaccinated and 163 (14%) had unknown vaccination status; 777 (68%) were considered to have preventable measles (i.e., were eligible for vaccination but unvaccinated). Among the 1,196 cases, 85 were single cases, and the remaining 1,111 represented 19 two-case chains and 34 outbreaks of 3 or more cases linked epidemiologically; the median outbreak size and duration was 6 cases (range, 3 to 452 cases) and 19.5 days (range, 5 to 205 days). A total of 934 (78%) of the 1196 cases and 13 (38%) of the 34 outbreaks occurred in under-immunized close-knit communities; eight outbreaks are ongoing.

Conclusion
Outbreaks of measles in the United States result from recurring measles introductions and subsequent measles spread, especially in under-immunized close-knit communities. To sustain measles elimination, it will be necessary to maintain timely routine high coverage with MMR vaccine, improve implementation of pretravel recommendations to minimize importations, and close immunity gaps in communities of US residents who remain unvaccinated.

Disclosures
All Authors: No reported Disclosures.