bluuebunny/crossref_metadata_2025_split huggingface dataset:
24. Antibiotic Use in Hospital Emergency Departments and Observation Settings from 2012–2018 in a Large Cohort of U.S. Hospitals
Authors: Preston Leigh Ellyn , Baggs James , Kabbani Sarah , Neuhauser Melinda M , King Laura M , Reddy Sujan , Hatfield Kelly M , Wolford Hannah , Kazakova Sophia , McCarthy Natalie , McDonald Clifford 
Published: January 2021

Abstract

Background
While discharge antibiotic prescriptions from emergency department (ED) visits have been reported, systemic antibiotic use during ED and hospital observation (OBS) visits have not been well assessed. We conducted a descriptive analysis of antibiotic use in these settings.

Methods
We identified ED and OBS visits not resulting in hospitalization, and systemic antibiotics administration charges during these visits from January 2012-December 2018 using the Premier Healthcare Database, representing at least 600 hospitals annually. Antibiotics prescribed after discharge were excluded. We reported the proportion of visits with antibiotic use, and described antibiotic use by class, agent and route stratified by location. We also examined trends in antibiotic use over time using a multivariable logistic model.

Results
We assessed 161,291,011 ED visits and 15,660,062 OBS visits from 2012–2018. Systemic antibiotics were identified in 9.0% of ED visits and 25.2% of OBS visits. Parenteral (IV) antibiotics were received in a high proportion of ED and OBS visits in which a systemic antibiotic was received (52.6% and 87.6% respectively). In the ED, 3rd/4th generation cephalosporins were the most commonly identified (32.7%) while in the OBS, 1st/2nd generation cephalosporins were most commonly identified (38.9%), Fig. 1. The most common agents in the ED were ceftriaxone, azithromycin, and cephalexin while the most common agents in the OBS were cefazolin, ceftriaxone, and levofloxacin. Any systemic antibiotic use in EDs declined slightly from 2012–2018 (9.2%-8.9%, p&lt; 0.0001) while use in OBS settings saw the largest increase from 2017- 2018 (25.4%-30.4%, p&lt; 0.0001), Fig. 2. Fluoroquinolone use decreased in both ED (41.3%) and OBS (31.2%) (both p&lt; 0.0001) beginning in years 2012 and 2016 respectively.
Figure 1: Antibiotic use in emergency departments and observation settings by antibiotic class, Premier Healthcare Database Hospitals, 2012–2018

Figure 2: Overall antibiotic use in emergency departments and observation settings by year, Premier Healthcare Database Hospitals, 2012–2018

Conclusion
Hospital ED and OBS settings are uniquely positioned to improve appropriate antibiotic use across the spectrum of healthcare. Frequent use of IV antibiotics and recent increases in antibiotic use in observation settings call for evaluation of appropriateness of their use and presence of transition-of-care process. Further evaluation of diagnoses to evaluate the appropriateness of IV administration may highlight additional opportunities for optimizing prescribing practices.

Disclosures
All Authors: No reported disclosures
32. Risk Factors for Vertical Transmission of t. Cruzi infection in an Endemic Setting
Authors: Klein Melissa D , Tinajeros Freddy , Malaga Edith , Verástegui Manuela , Condori Beth J , Urquizu Federico , Gilman Robert , Bowman Natalie M 
Published: January 2021

Abstract

Members of the Chagas Disease Working Group in Peru and Bolivia include
Edith Hinojosa, Clariza Chavez, Jean Karla Velarde, Carla Chavarria, Victoria Serrudo, Roberto Araya, Alcides Buitron, Rita Mendieta, Holger Mayta, Maritza Calderon, Holger Mayta and Yagahira Castro.

Background
Vertical transmission of Trypanosoma cruzi infection accounts for a growing proportion of new cases of Chagas disease. Congenital infection is curable if treated promptly, but the majority of infected infants do not receive timely diagnosis or treatment. Better risk stratification is needed to predict which women are more likely to transmit the infection.

Methods
This study enrolled women who presented for delivery and their infants at the Percy Boland Women’s Hospital in Santa Cruz, Bolivia. Pregnant women were screened for Chagas disease by rapid test. The infants of seropositive mothers underwent diagnostic testing with microscopy (“micromethod”) and quantitative polymerase chain reaction (qPCR) as newborns and at one- and nine-month follow-up. Mothers completed surveys about demographics and medical history.

Results
Among 5,828 enrolled women, 1,271 (21.8%) screened positive for Chagas disease. Of the 1,325 infants of seropositive mothers, 113 (8.5%) were diagnosed with congenital Chagas disease by microscopy or qPCR. Cesarean delivery was significantly associated with lower odds of vertical transmission (adjusted OR: 0.63, 95% CI: 0.41–0.98, p=0.040). Congenital infection was more common in twins (adjusted OR: 3.30, 95% CI: 1.97–5.54, p&lt; 0.001) and male infants (adjusted OR: 1.50, 95% CI: 1.01–1.22, p=0.045).

Conclusion
Our findings suggest that Cesarean delivery may be protective against vertical transmission of T. cruzi, while twins and male infants may have an increased risk. A better understanding of risk stratification for congenital Chagas disease may help improve regional initiatives to reduce disease burden.

Disclosures
All Authors: No reported disclosures
35. Missed and Unrecorded Drug Use Among Infective Endocarditis Cases Is Associated with Underestimated Burden of Disease and Fragmented Care: Evidence from Six States
Authors: Christine Paul , Usher Michael , Pham Cuong , Kelly Ryan , Winkelman Tyler 
Published: January 2021

Abstract

Background
Studies using national administrative data suggest that hospitalizations for drug use-associated infective endocarditis (DUA-IE) have increased over the last ten years. However, drug use as a contributing factor to IE hospitalizations is often missed or not included in coding documentation, resulting in undercount of DUA-IE. We assessed whether missed drug use during IE hospitalizations was associated with higher levels of fragmented care and underestimation of DUA-IE burden.

Methods
We analyzed data from State Inpatient Databases and State Emergency Department Databases from six states (FL, GA, IA, NY, UT, VT) from 2011–2015. Patients older than 16 with ICD-9/10 codes for admissions with IE were included. IE was categorized as DUA using ICD-9/10 codes for drugs/conditions associated with injection drug use. We labeled IE cases as a “missed” DUA-IE case if they had no diagnosis of drug use during their index hospitalization but received a drug use diagnosis during an ED visit or inpatient stay in the calendar year of their index IE hospitalization. We compared “missed” DUA-IE cases to DUA-IE cases where drug use was identified in the index hospitalization and non-DUE-IE cases with respect to demographics, length of stay (LOS) and total charges. To assess care fragmentation, we stratified IE groups by whether the patient was admitted to 1 or &gt;1 hospital within 90-days of the index IE admission.

Results
There were 52147 non-DUA-IE cases, 6872 DUA-IE cases, and 2676 “missed” DUA-IE cases identified by linking drug use across multiple encounters. Missed cases represented a 39% increase in total DUA-IE cases. Compared to DUA-IE cases identified at index hospitalizations, missed cases were more likely to be older, Black, insured by Medicare, and from rural areas. They also had higher 30-day readmission rate (23.2% vs 14.5%, p&lt; 0.001) and higher charges (p&lt; 0.001), with similar LOS. Fragmented care was most common among patients with missed DUA-IE (33.3%), followed by DUA-IE cases identified during index hospitalization (20.5%) and non-DUA-IE cases (13.7%).
Table 1

Table 2

Conclusion
Missed and/or unrecorded drug use and fragmented care are common features of DUA-IE. This results in underestimation of both DUA-IE prevalence and hospital utilization due to DUA-IE.

Disclosures
All Authors: No reported disclosures
40. The Impact of Medically Assisted Therapy for Opiate Use Disorder in staphylococcus Aureus Bacteremia Patients Within a Large Hospital System - A Retrospective Cohort Study
Authors: Keene Brooks A , Saboori Shadi , Meredith Jacqueline , King Deanna , Polk Christopher , Leonard Michael 
Published: January 2021

Abstract

Background
Intravenous drug use (IVDU) is a risk factor for development of S. aureus bacteremia (SAB) and prevalent in opiate use disorder (OUD). While the standard of care involves treating the underlying OUD with medically assisted therapy (MAT), it is unknown how much impact this has on clinical endpoints.

Methods
We conducted a retrospective cohort study of patients with IVDU with hospitalizations for SAB during a 28-month period from 9/2016 through 12/2018 in 10 urban and rural North Carolina hospitals in a single large health system. We compared outcomes for patients receiving prescription for MAT at discharge versus no MAT at discharge. MAT was defined as receiving methadone, buprenorphine, or naltrexone. Patients who expired inpatient were excluded from analysis. Clinical endpoints were 30- and 90-day mortality and 30-day SAB-related readmissions.

Results
Of the 174 patients, 28% received a prescription for MAT at discharge. The majority of the patients were Caucasian (88%), female (57%), with mean age of 37 years. Factors that significantly increased likelihood of MAT at discharge were female gender (34% vs 20%, p=0.04), having a complicated SAB (33% vs 28%, p=0.01), presence of a spinal/epidural abscess (57% vs 43%, p=0.002), and increased length of stay (LOS) (37 days vs 24 days, p=&lt; 0.001). No difference in 30- and 90-day mortality was observed; only one patient in each group died within 90 days. Prescription for any MAT at discharge was associated with a significant decrease in the risk of SAB-related 30-day readmission (0% vs 17%, p=0.002).
Table 1: Baseline Characteristics

Table 2: MAT & Clinical Outcomes in S. aureus Bacteremia

Figure 1: Medically Assisted Therapy Prescribed at Discharge

Conclusion
Gender, more complicated infections, and prolonged LOS may increase the likelihood of receiving a prescription for MAT at discharge. MAT prescription at discharge may decrease the risk of 30-day SAB related readmission (NNT 5.9). The results suggest that provision of MAT to patients with SAB and history of IVDU should be incorporated into standardized treatment guidelines.

Disclosures
All Authors: No reported disclosures
41. Impact of Gut Microbiome Changes on Hematopoietic Stem Cell Transplantation Outcomes in Children
Authors: Teherani Mehgan , Pratte Zoe , Banskota Samridhi , Gulick Dalia , Djeddar Naima , Gillespie Scott , Gibson Gregory , Qayed Muna 
Published: January 2021

Abstract

Background
In adults undergoing allogeneic hematopoietic cell transplantation (HCT), higher gut microbiome diversity is associated with reduced bloodstream infections (BSI) and improved overall survival (OS). Rifaximin prophylaxis in adult HCT helps to maintain microbiome diversity. We examine changes in microbiome in a cohort of pediatric patients undergoing HCT.

Methods
Patients were enrolled in an institutional biorepository (n=82) with a subset enrolled in an ongoing trial using rifaximin (n=21) between 2013–2020. All patients had HCT for a hematologic malignancy, using myeloablative conditioning. Patients in the rifaximin trial received rifaximin starting 7 days before HCT (D-7) through D+28, otherwise, no prophylactic antibiotics were used. Systemic antibiotic timing was categorized as none, early (≤ Day 0, day of HCT), and late (&gt; D0). We performed 16s rRNA sequencing from stool for 73 subjects, at baseline (D-7), and weekly through D+28 (engraftment). Microbiome diversity was assessed by Shannon index.

Results
Median age was 9 years (range 1–20), 59% male, 41% Caucasian and 29% Black. There were no differences in BSI or mortality by age, sex, or race.
Microbiome diversity changed significantly over time (p=0.008). Drop in diversity was most notable in patients who had early antibiotics (Mean=1.4, CI -0.15, 2.94, p=0.077). Higher diversity was seen when patients received none or late versus early antibiotics, but this was not statistically significant (Figure 1, p=0.23). Piperacillin-tazobactam was used empirically in 91% of patients. OS at 1 year was 88.5% (CI 68.4%, 96.1%) for patients with high (≥ median) D+28 diversity compared to 60% (CI 38.4%, 76.1%) for patients with low diversity (Figure 2, p=0.018) Only 1 of 21 (4.8%) in the rifaximin group developed a BSI with a gut bacterium compared to 8 of 61 (13.1%) not on rifaximin within the first 30 days (trial enrollment ongoing).
Figure 1. Effect of systemic antibiotic timing on microbiome diversity over time.

Figure 2. One-year overall survival of patients with high (&gt;2.77) versus low (&lt;2.77) diversity defined by median Shannon-Index.

Conclusion
We have shown a significant correlation between engraftment microbiome diversity and 1-year OS. Early antibiotic exposure was detrimental to microbiome diversity. Approaches to preserve microbiome diversity and prevent BSI are likely to improve HCT outcomes. Our ongoing trial using rifaximin will provide preliminary data regarding this approach.

Disclosures
All Authors: No reported disclosures
42. Common Population Variants Cause Susceptibility to Disseminated Coccidioidomycosis
Authors: Hsu Amy P , Davis Joie , Chaput Alexandria L , Powell Daniel A , Pouladi Nima , Lussier Yves , Fierer Joshua , Frelinger Jeffrey A , Galgiani John N , Lionakis Michail , Holland Steven M 
Published: January 2021

Abstract

Background
Coccidioides are endemic, dimorphic fungi found in soils of southwestern United States, Mexico and Central America. Infection occurs via inhalation of arthroconidia which swell, differentiate into spherules and rupture releasing endospores. While the majority of infected individuals will never report illness, roughly 1/3 seek medical attention for fungal pneumonia and ~1% of those present with disseminated coccidioidomycosis (DCM). IL12-IFNγ pathway mutations have been reported in DCM but are exceedingly rare and cannot account for the ~500–600 cases of DCM/year.

Methods
We performed whole exome sequencing on 66 individuals with DCM, retaining variants predicted damaging (CADD &gt;15) with a population frequency &lt; 10%.

Results
Homozygous CLEC7A c.714T &gt;G; p.Y238* causing a truncated Dectin-1 receptor was overrepresented (OR=9.8449, 95% CI 3.0841 to 31.4260, P=0.0001). Dectin-1 signaling pathway variants included 3 homozygous and 11 heterozygous CLEC7A p.Y238* individuals, one each CLEC7A p.I223S and MALT1 p.R149Q and five PLCG2 p.R268W. Since Dectin-1 is the receptor for b-glucan, a major Coccidioides cell-wall component, we hypothesized that Dectin-1 pathway variants could affect fungal recognition and cellular response. Healthy control PBMCs stimulated with purified β-glucan or heat-killed Candida albicans induced 6-fold more TNFα than patients with homozygous or heterozygous CLEC7A, PLCG2 or MALT1 variants (P=0.0022, Ordinary one-way ANOVA). Additionally, one patient with a family history of DCM but lacking a defined mutation also failed to up-regulate TNFα after stimulation.
Normalized TNF production from healthy control and DCM patient’s peripheral blood mononuclear cells

Conclusion

These data are consonant with increased dissemination in Clec7a-/- mice as well as in patients receiving anti-TNF biologics. These gene variants accounted for 31% of our DCM cohort (21/66 patients). This is the first demonstration of variants outside the IL12-IFNg pathway impairing fungal recognition and cellular response in coccidioidomycosis. Common heterozygous variants may be sufficient for disease susceptibility to highly pathogenic organisms.

Disclosures
Michail Lionakis, MD, ScD, Matinas BioPharma (Research Grant or Support)
44. In-host Infection Dynamics Of Pseudomonas Aeruginosa Pneumonia
Authors: Bachta Kelly E R , Allen Jonathan P , Hauser Alan R 
Published: January 2021

Abstract

Background
Pseudomonas aeruginosa (PA) is an important cause of healthcare-associated infections including pneumonia and bloodstream infections (bacteremia). PA pneumonia is a significant cause of morbidity and mortality, especially in immunocompromised patients and those on prolonged mechanical ventilation; However, little is known about the in-host infection dynamics of PA pneumonia and its relationship to transmission.

Methods
We utilized a mouse model in conjunction with sequencing technology to dissect the infection dynamics of PA pneumonia. BALB/c mice were challenged intranasally with a clinical isolate, PABL012. At various time points post infection, organs were harvested and the surviving PA enumerated. STAMP (sequence tag-based analysis of microbial populations) analysis was applied to define the in-host infection dynamics.

Results
Bacterial enumeration revealed that PA disseminates early and widely in intranasally infected animals. Infected mice shed significant amounts of PA in their gastrointestinal tract (GI). Finally, STAMP analysis revealed that compared to bloodstream infections where PA experiences a severe in vivo bottleneck when trafficking to GI tract, PA disseminates freely from the lungs to the GI tract with little bottleneck effect.

Conclusion
Our research, using murine models, sheds light on the infection dynamics of PA pneumonia. Our results suggest that the lungs are a unique environment in which PA replicates unchecked and experiences little bottleneck effect. This unchecked replication likely seeds the gastrointestinal tract and promotes significant fecal excretion. Fecal excretion of PA from hospitalized patients is observed, but the direct link between pneumonia, GI shedding, and transmission remains unclear. Our observations have significant implications for infection control and shed light on how PA might exit the human host into the healthcare environment setting the stage for a transmission event.

Disclosures
All Authors: No reported disclosures
45. In Silico Identification of Virulence Factors That May Contribute to Enhanced Gut Colonization of ESBL e. Coli
Authors: Diaz Alondra , Whitmer Grant R , Arshad Mehreen 
Published: January 2021

Abstract

Background
The rapid global spread of extended spectrum beta lactamase-producing Escherichia coli (ESBL-E) strains threatens our ability to the treat many common infections and have become a major threat to public health. Some ESBL-E have a fitness advantage allowing them a competitive edge in gut colonization contributing to their global spread. We aimed to conduct in silico molecular characterization of virulence factors that may contribute to this fitness advantage.

Methods
For this observational study, we report data from fifteen whole-genome sequenced ESBL-E isolates found in the stool of a cohort of otherwise healthy infants. These strains were compared to MG1655 (commensal E. coli) and UTI89 (pan-sensitive uropathogenic E. coli). Phenotypic growth curves were done in minimal media with glucose as the only carbohydrate source. The genome sequences were assembled and annotated using Pathosystems Resource Integration Center (PATRIC) database and used to predict antibiotic resistance genes (ARGs) as well as virulence factors that may be driving the competitive advantage of these strains.

Results
All ESBL E. coli strains encoded multiple ARGs including those that target beta-lactams, aminoglycosides, fluoroquinolones, tetracyclines and macrolides. Growth curves in minimal media showed enhanced growth of some ESBL E. coli compared to control strains (Figure 1). ESBL-E strains 7 and 8 were also shown to have a higher copy number of carbohydrate metabolism genes. Proteome comparison of ESBL-E to MG1655 or UTI89 identified 93 and 321 proteins, respectively, with &lt; 50% homology to the corresponding protein in the comparator strains (Figure 2). However, only 29 proteins across all ESBL-E were showed non-homology to both MG1655 and UTI89. These included both fimbrial and phosphotransferase system proteins.
Figure 1

Figure 2A

Figure 2B

Conclusion
ESBL-E strains may use a combination of attributes to out-compete commensal or non-resistant E. coli. These may include enhanced carbohydrate metabolism, increased adherence to the epithelial cells (via fimbrial proteins) or greater efficiency of carbohydrate uptake from the environment (via the phosphotransferase system). Further in vitro and in vivo studies are in progress to verify these in silico observations.

Disclosures
All Authors: No reported disclosures
1. The Impact of Behavioral Nudges, Communication Training and Assessment and Feedback on Adolescent Vaccination Rates and Parent Satisfaction
Authors: Bradley-Ewing Andrea , Goggin Kathy , Meredith Georgann , Lee Brian R , Li Susan , Doctor Jason , Myers Angela 
Published: January 2021

Abstract

Background
Effective prevention of HPV is possible, but &lt; 50% of adolescents in the Midwest complete the recommended vaccine series. Strategies to increase HPV vaccination rates have demonstrated efficacy, however widespread implementation of these interventions has not been realized. Behavioral nudges have demonstrated efficacy in increasing uptake of desired heath behaviors among providers (e.g. hand hygiene, judicious antibiotic prescribing). This trial assessed the impact of an assessment and feedback, communication training, and behavioral nudge (i.e. poster-sized vaccine commitment statements) intervention (T3) on adolescent vaccination rates and parental satisfaction at four Midwestern pediatric practices.

Methods
Practices were randomly assigned to receive either 1) assessment and feedback or 2) T3 intervention. Providers (n=16) completed surveys regarding vaccine polices and parents of vaccine eligible adolescents (n=230) reported their child’s vaccine history and satisfaction with the consultation. Practice- level vaccination rates for Tdap, Meningococcal, and HPV were calculated through billing data queries from an integrated pediatric health network. Vaccination rates and provider/ parental responses were compared by intervention arm.

Results
All practices evidenced increased adolescent vaccine rates, ranging from 0.8% to 3.4% for Meningococcal and 1.3% to 12.1% for Tdap. Three of the four practices had increased HPV vaccination rates (1% to 10%), however there was no statistically significant difference by study arm. Most parents (M age 41.34; SD 8.05; 85% female, 68% White) indicated their child had previously initiated the HPV vaccine series (61%) and 72% indicated receipt of an HPV vaccine during the study visit. Concerns among HPV vaccine hesitant parents (n=60) included concerns about vaccine safety and necessity. Most (97%) of parents were satisfied with their consultation.

Conclusion
Practices in both intervention groups evidenced an increase in adolescent vaccination rates. While some parents had concerns about HPV vaccine safety and necessity, parents welcomed discussions about HPV vaccine and were satisfied with their provider’s communication regardless of their vaccine decisions.

Disclosures
Brian R. Lee, MPH, PhD, Merck (Grant/Research Support)