bluuebunny/crossref_metadata_2025_split huggingface dataset:
800. Oral Vancomycin Prophylaxis Against Clostridioides difficile in Patients Admitted to a Tertiary Academic Medical Center
Authors: Kopelman David B , Wright Sharon B , Gold Howard , Mehrotra Preeti , Mehrotra Preeti 
Published: January 2021

Abstract

Background
In an effort to more accurately diagnose Clostridioides difficile infection (CDI), many hospitals have switched to two-step testing algorithms that rely on nucleic acid amplification testing with reflex enzyme immunoassay for toxin. Additionally, oral vancomycin prophylaxis (OVP) against CDI is increasingly being used; initial studies focused on preventing recurrence in patients with a prior history of CDI, but OVP is also being studied in primary prevention. We hypothesized that following the implementation of two-step testing, clinicians may use OVP for prevention of a patient’s first episode of CDI based on knowledge of prior PCR+/Toxin- testing.

Methods
We performed a single-center, retrospective cohort study of patients admitted to Beth Israel Deaconess Medical Center. We identified patients who received oral vancomycin once daily or BID for the prevention of CDI following implementation of two-step testing. Patients who received oral vancomycin as part of a taper following acute infection were excluded. We categorized rationale for prophylaxis based on clinical documentation and collected details of patients’ CDI history, antibiotic exposure, and subsequent CDI testing during hospitalization.

Results
In the 12 months following implementation of two-step testing, there were 80 patients who received OVP during hospitalization (2 daily and 78 BID). The vast majority (73, 91.3%) had a history of CDI and received OVP for secondary prevention while receiving systemic antibiotics. There were only 3 patients (3.8%) without known clinical history of CDI whose clinicians documented prophylaxis based on previous PCR+/Toxin- testing. Patients on OVP received a mean of 4.1 systemic antibiotics during hospitalization. When continuing OVP for a finite period after discontinuation of systemic antibiotics, this was most commonly done for 2-7 days (16 of 26, 61.5%). 22 patients underwent stool testing for CDI while receiving OVP in the hospital and all resulted PCR-negative.
OVP Indication

OVP Duration

Conclusion
Following implementation of two-step testing for CDI, use of OVP for primary prevention based solely on knowledge of PCR+/Toxin- testing in patients without a history of CDI was rare. Acute CDI appears unlikely in patients actively receiving OVP.

Disclosures
All Authors: No reported disclosures
804. Use of a Trained Canine to Detect Clostridioides difficile in the Hospital Environment
Authors: Harrison Rachael M , Cook Paul P 
Published: January 2021

Abstract

Background
Clostridioides difficile infection (CDI) is the most common nosocomial infection in this country. The organism forms spores, which likely contribute to spread of infection in the hospital setting. Current guidelines call for special cleaning of rooms following discharge of patients who tested positive for CDI. There are currently no means to validate that cleaning has eradicated all of the spores. Canines (dogs) have been used to detect a variety of odors because of their superior olfactory abilities. A beagle was trained to detect the odor of C. difficile in the hospital setting.
Harley the Clostridium difficile sniffing canine.

Methods
C. difficile was grown at the microbiology department at Vidant Medical Center (VMC). Culture plates containing the organism were used by a professional trainer to train a two-year old female beagle dog. The canine was taught to sit when she identified the odor. The canine was given positive reinforcement with oral treats each time she identified the odor. Once the dog was proficient in identifying the organism, the trainer used clinical stool specimens that tested either positive or negative for C. difficile. Prior to coming into the hospital setting, the canine was able to identify positive stool samples with near 100% accuracy. The dog was brought to search rooms occupied or previously occupied by patients who had CDI. The study was approved by the Animal Use and Care Committee at East Carolina University and took place between October 2019 and March 2020 at VMC.

Results
The canine detected the presence of C. difficile in 51% of 47 rooms inhabited by patients currently being treated for CDI and in 46% of 28 rooms previously inhabited by patients that tested positive for CDI. In all positive rooms, the organism was detected on the bedrails. She did not detect C. difficile in any positive areas after they had been cleaned with bleach wipes.
Rooms found to be positive by canine.

Conclusion
Training a canine to detect C. difficile is an effective means of detecting the organism in the hospital environment. Use of a trained dog appears to be effective in validating the cleaning process of rooms that have been previously occupied by patients with CDI.

Disclosures
Paul P. Cook, MD, Contrafect (Grant/Research Support, Scientific Research Study Investigator)Gilead (Grant/Research Support, Scientific Research Study Investigator)Leonard-Meron (Grant/Research Support, Scientific Research Study Investigator)Lilly (Grant/Research Support, Scientific Research Study Investigator)
808. Evaluating the Incidence of Bacteriuria in Female Patients Before and After Implementation of External Catheter Devices
Authors: Noval Mandee , Leekha Surbhi , Bhatt Meghna , Armhazizer Michael , Celotto Abigale , Claeys Kimberly C 
Published: January 2021

Abstract

Background
Bacteriuria associated with indwelling urinary catheters is commonly linked to inappropriate antibiotic use in hospitals. The use of external catheter devices (ECD) has increased in recent years to reduce bacteriuria risk in women, based on data in male patients. Currently no studies have shown a similar benefit in the female population.

Methods
This was a quasi-experimental study among adult female ICU patients with urinary catheters (indwelling or external) between 12/2015 – 5/2017 (pre-ECD) and 12/2017 – 6/2019 (post-ECD). The primary outcome was the incidence of positive urine cultures pre- vs post-intervention. An a priori subgroup patient-level analysis evaluated positive urine cultures and antibiotic use pre- vs post-intervention in medical and surgical ICU patients who had a urinalysis ordered in the presence of an indwelling or external urinary catheter. Antibiotic use was considered appropriate when prescribed in the presence of a positive urine culture, clinical signs and symptoms of UTI, and a UTI order indication.

Results
There were 4,640 patient ICU encounters during the study period; 2,201 pre- vs 2,439 post-intervention. Mean age was 59.2 (SD 15.4) years, median Elixhauser Score was 6 (IQR 4, 7), and there were no significant differences between groups. In the overall cohort, there was a decrease in the monthly rate of indwelling urinary catheter use pre- versus post- intervention (Figure 1) of 182/1,000 vs 166/1,000 patient days, P = 0.03. There was also a decrease in rate of positive urine cultures from pre- to post- intervention (38/1,000 vs 28/1,000 patient days, P = 0.004). Antibiotic days of therapy (DOTs) for UTI indication was similar in the pre- versus post-intervention groups with 1.9/1000 vs. 1.8 DOT/1,000 patient days (P = 0.7). In the subgroup of 210 patients (73 pre- vs 137 post-intervention) who underwent urinalysis, there was also a decrease in the proportion of positive urine cultures from pre- to post-intervention (42.5% vs. 24.3%; P = 0.007). Of patient receiving antibiotics for UTI indication, appropriateness was numerically higher post-intervention (9.1% vs. 31.6%; P = 0.21).

Conclusion
The use of external urinary catheters may be beneficial in reducing bacteriuria and related antibiotic use among female ICU patients.

Disclosures
All Authors: No reported disclosures
LB-1. Efficacy and Safety of Oral Sulopenem Etzadroxil/Probenecid Versus Oral Ciprofloxacin in the Treatment of Uncomplicated Urinary Tract Infections (uUTI) in Adult Women: Results from the SURE-1 Trial
Authors: Dunne Michael W , Das Anita F , Zelasky Michael , Akinapelli Karthik , Boucher Helen , Aronin Steven I 
Published: January 2021

Abstract

Background
Sulopenem is a broad-spectrum IV and oral penem antibiotic being developed for the treatment of infections caused by multidrug-resistant bacteria.
Overall and Clinical Success in Patients with an Uncomplicated UTI at Test of Cure (TOC) and End of Treatment (EOT)

Methods
1,671 adult women with pyuria, bacteriuria, and signs and symptoms of uUTI were randomized to sulopenem etzadroxil/probenecid bid for 5 days or ciprofloxacin bid for 3 days. Two independent primary analyses, each with a separate alpha assigned, were incorporated into the design of the study with the primary endpoint being overall success (combined clinical and microbiologic success) at the Test of Cure (TOC) visit. In the micro-MITTR population (patients with baseline pathogen resistant to ciprofloxacin), sulopenem was compared for superiority over ciprofloxacin; in the micro-MITTS population (patients with baseline pathogen susceptible to ciprofloxacin), the two agents were compared for non-inferiority. Using a pre-specified hierarchical testing procedure (Westfall 2001), the primary efficacy endpoint was then to be further tested if either superiority or non-inferiority was declared in the MITTR or MITTS populations, respectively.

Results
In the micro-MITTR population, sulopenem demonstrated superiority to ciprofloxacin (p &lt; 0.001). In the micro-MITTS population, sulopenem was not non-inferior to ciprofloxacin for the primary endpoint, driven primarily by the higher rate of asymptomatic bacteriuria post treatment in patients on sulopenem. In the combined analysis of all randomized patients with an organism identified at baseline (MITTR+MITTS), sulopenem was non-inferior to ciprofloxacin.
Treatment emergent adverse events occurred more frequently in sulopenem patients (all, 24.8% vs 13.9%; related, 17.0% vs 6.2%), accounted for by a higher incidence of self-limited diarrhea (12.4% vs 2.5%). Serious adverse events were similar on each regimen.

Conclusion
Sulopenem was superior to ciprofloxacin for the treatment of adult women with uUTI due to quinolone non-susceptible pathogens. Sulopenem was not non-inferior in the treatment of quinolone susceptible pathogens, driven by a lower rate of asymptomatic bacteriuria in patients receiving ciprofloxacin, but was non-inferior in the combined population of patients.

Disclosures
Michael W. Dunne, MD, Iterum Therapeutics (Employee, Shareholder) Anita F. Das, PhD, Iterum Therapeutics (Consultant) Michael Zelasky, BS, Iterum Therapeutics (Employee) Karthik Akinapelli, BS, Iterum Therapeutics (Employee) Steven I. Aronin, MD, Iterum Therapeutics (Employee)
LB-2. Relative Effectiveness of aIIV3 versus IIV4 and HD-IIV3 In Preventing Influenza-Related Medical Encounters in Adults ≥65 Years of Age at High Risk for Influenza Complications During the U.S. 2017–2018 and 2018–2019 Influenza Seasons
Authors: Fischer Lauren , O'Brien Dan , Vasey Joseph , Sylvester Gregg C , Mansi James A 
Published: January 2021

Abstract

Background
Individuals with health conditions have shown higher rates of influenza-related morbidity and mortality compared to healthy individuals and are often prioritized for influenza vaccination. However, vaccination with egg-derived standard quadrivalent inactivated influenza vaccines (IIV4) has shown to be less effective in adults ≥65 years of age largely due to immunosenecence. Two enhanced vaccines, the MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and a high-dose trivalent inactivated influenza vaccine (HD-IIV3), were developed to provide adults ≥65 years with increased protection. The objective of this study was to determine the relative vaccine effectiveness (rVE) of aIIV3 versus IIV4 and HD-IIV3 in preventing influenza-related medical encounters in high-risk adults ≥65 years.

Methods
A retrospective cohort study was conducted among adults ≥65 years with ≥1 health condition with a record of receiving either aIIV3, IIV4 or HD-IIV3 in the 2017–18 or 2018–19 influenza seasons. Patient-level electronic medical records linked to pharmacy and medical claims were used to ascertain exposure, outcome and covariate information. The primary outcome was influenza-related medical encounters in primary care and hospital (ICD-10 codes J09*–J11*). Inverse probability of treatment weighting was used to obtain odds ratios (ORs) adjusted for age, sex, race, ethnicity, geographic region, comorbidities and week of vaccination for each health condition. rVE was determined using the formula (1-OR)*100 and reported with 95% confidence intervals (CI).

Results
Overall, 1,755,420 individuals with ≥1 health condition were included for analysis in the 2017–18 season and 2,055,012 individuals in the 2018–19 season. In both seasons, high-risk subjects who received aIIV3 had statistically significantly greater reduction in influenza-related medical encounters as compared to IIV4 (Table 1). Non-statistically significant estimates preclude definitive conclusions for comparisons with HD-IIV3.
Table 1. Adjusted relative vaccine effectiveness (rVE) of aIIV3 versus comparators in high-risk patients in the 2017–2018 and 2018–2019 influenza seasons in the U.S.

Conclusion
The results of this study support the use of aIIV3 in adults ≥65 years of age at high risk for influenza complications and provides further evidence supporting aIIV3 as an effective public health measure against influenza.

Disclosures
Lauren Fischer, M.A., Seqirus (Consultant) Dan O'Brien, BA, Seqirus (Consultant) Joseph Vasey, PhD, Seqirus (Consultant) Gregg C. Sylvester, MD, Seqirus (Employee) James A. Mansi, PhD, Seqirus (Employee)
LB-11. Comparison of Viral Loads in Individuals With or Without Symptoms At Time of COVID-19 Testing Among 32,480 Residents and Staff of Nursing Homes and Assisted Living Facilities in Massachusetts
Authors: Lennon Niall J , Mina Michael , Rehm Heidi L , Hung Deborah T , Smole Sandra , Woolley Ann E , Lander Eric , Gabriel Stacey 
Published: January 2021

Abstract

Background
Transmission of COVID-19 from people without symptoms confounds public health containment strategies. Comprehensive cross-sectional screening enables assessment of viral load independent of symptoms, informing transmission risks. We quantified SARS-CoV-2 burden by RT-qPCR from comprehensive screening of nursing homes and assisted living facilities in Massachusetts to inform our ability to detect SARS-CoV-2 in individuals with or without symptoms.

Methods
From 4/9/20 to 6/9/20, we tested nasopharyngeal (NP) swabs from 32,480 unique individuals comprising staff and residents of the majority of nursing homes and assisted living facilities in Massachusetts. Symptomatology at the time of sampling and demographic information were provided by each facility. NP swabs were collected, RNA extracted, and SARS-CoV-2 testing performed by RT-qPCR. We compared cycle thresholds (Ct) with a standard curve to quantify viral loads.

Results
The nursing home and assisted living facilities resident cohort (N = 16,966) was 65% female with mean age 82. The staff cohort (N = 15,514) was 76% female with mean age 45. In all, 2654 residents (15.5%) and 624 staff (4.1%) tested positive for SARS-CoV-2, including 12.7% of residents and 3.7% of staff without symptoms, compared to 53.1% of residents and 18.2% of staff with symptoms. The Ct distributions for viral probes were very similar between populations with and without symptoms (Fig 1), with a statistically but not meaningfully different mean (ΔCt 0.71 cycles, p = 0.006) and a similar range (12–38 cycles). This similarity persisted across all sub-categories examined (age, race, ethnicity, sex, resident/staff).
Figure 1

Conclusion
In a large cohort of individuals screened for SARS-CoV-2 by RT-qPCR, we found strikingly similar viral load distributions in patients with or without symptoms at the time of testing. The size of the study population, including both staff and residents spanning a wide range of ages, provides a comprehensive cross-sectional point prevalence measurement of viral burden. Because the distributions of viral loads are very similar regardless of symptoms, existing testing modalities validated for detection of SARS-CoV-2 RNA in symptomatic patients should perform similarly well in individuals without symptoms at the time of testing.

Disclosures
All Authors: No reported disclosures
LB-12. SARS-CoV-2 RNA and Antibodies among People Experiencing Homelessness and Staying in Shelters or Outdoor Encampments in Denver, Colorado, May-July 2020
Authors: McCormick David , Scott Tracy , Chavez Jesse , Wilcox Kay , Marx Grace E , Stella Sarah A , Wendel Karen , Burman William 
Published: January 2021

Abstract

Background
The COVID-19 pandemic has disproportionately affected people experiencing homelessness (PEH) residing in shelters. Initial and regular testing of PEH in communities with moderate or substantial SARS-CoV-2 transmission may limit spread in shelters. We analyzed factors associated with positive SARS-CoV-2 RNA and antibody tests for PEH staying in shelters or encampments in Denver, Colorado.

Methods
In May 2020, Denver Public Health collaborated with local leaders to identify 4 homeless shelters and 3 outdoor encampments for voluntary, universal SARS-CoV-2 testing. At each testing event, a short questionnaire including sociodemographic factors and symptoms was administered to PEH who consented to testing. SARS-CoV-2 RNA testing by reverse transcription polymerase chain reaction (RT-PCR) was performed on nasopharyngeal swabs; antibody testing was performed on venous blood samples. PEH reporting a prior positive RT-PCR test were not retested but were eligible for antibody testing. Statistical calculations were performed with an α of 0.05; all tests were two-sided.

Results
From June 2–July 28, 2020, 931 PEH were approached. A total of 863 RT-PCR tests were performed at 14 testing events, and 334 antibody tests were performed at 5 testing events. Overall, 604 and 259 RT-PCR tests were conducted in 4 shelters and 3 encampments, respectively; 189 and 145 antibody tests were conducted in 3 shelters and 2 encampments, respectively. PEH tested in shelters were older, more often men, less often Native American, and less likely to report COVID-19 symptoms than those tested at encampments (Table 1). Overall, 9% of PEH tested in shelters tested positive for SARS-CoV-2 compared to 3% of PEH tested in encampments (p=0.002); 8% of men had positive RT-PCR results compared to 2% of women (p=0.03) (Table 2). PEH tested at shelters had a higher percentage of detectable SARS-CoV-2 antibodies than those tested in encampments (24% vs 8%, p=0.0002; Table 3). Neither RT-PCR nor antibody test results differed significantly by race or ethnicity.
Table 1. Demographics of participants residing in encampments compared with shelters in Denver, Colorado, May-July 2020 (n=931)

Table 2. Comparison of participants testing positive or negative for SARS-CoV-2 RT-PCR* by location and demographics, in Denver, Colorado, May-July 2020

Table 3. Comparison of participants testing positive or negative for antibodies against SARS-CoV-2 by location and demographics in Denver, Colorado, May-July 2020

Conclusion
A greater percentage of PEH tested positive for both SARS-CoV-2 RNA and antibodies at shelters than encampments, suggesting that continued assessment of mitigation strategies in shelters should be a priority.

Disclosures
All Authors: No reported disclosures
LB-15. A Trans-Governmental Collaborative Effort to Independently Evaluate SARS-CoV-2 Serology Assays Using Well-Characterized Sample Panels
Authors: Shawar Ribhi , O’Leary Brendan , Kemp Troy , Cherry James , Owen S Michele , Gallagher Pamela , Thornburg Natalie , Kondratovich Marina , Satheshkumar Panayampalli Subbian , Schuh Amy , Lester Sandra , Cassetti Cristina , Cassetti Cristina , Lowy Douglas , Gitterman Steve R 
Published: January 2021

Abstract

Background
The emergence of the novel coronavirus, SARS-CoV-2, created a crucial need for accurate tests for diagnosis, assessment of prior infection, and understanding its natural history. Serology assays play an important role in the assessment of anti-viral immune responses and previous infections. Evaluation of serology assays with well-characterized serum and/or plasma samples is critical to determine assay performance. CDC, FDA and NCI’s Frederick National Laboratory for Cancer Research (NCI-FNLCR) have established a collaborative network to independently evaluate commercial antibody tests prior to their authorization.

Methods
Positive (n=30) serum samples with a range of anti-SARS-CoV-2 antibody titers (Table) and negative (n=80) serum and/or plasma samples were selected to establish performance evaluation panels (PEVs). Three PEVs with similar overall antibody titer distribution have been created. Negative samples were collected prior to 2020, before the SARS-CoV-2 pandemic. Positive samples were from patients previously confirmed to have SARS-CoV-2 using a nucleic acid amplification test. Each sample was characterized at CDC and NCI-FNLCR for presence/absence of SARS-CoV-2 IgM and IgG antibodies using a SARS-CoV-2 spike enzyme linked immunosorbent assay (ELISA). NCI-FNLCR also performed a SARS-CoV-2 spike Receptor Binding Domain (RBD) IgG ELISA. Positive samples were assessed at multiple dilutions. Manufacturers submitted their serology assays for evaluation by this program. The sensitivity of each test was assessed for each antibody class (IgG and IgM) and in a combined manner, where a positive result for either antibody was considered as a positive result. For combined specificity, a negative result meant a sample was negative for both antibodies (IgG and IgM).
Number of positive samples with anti-SARS-CoV-2 spike antibodies for each panel (n=30)

Results
To date, 53 serology assays have been evaluated. Sensitivity ranged from 30.0% to 100% for IgG, from 10.0% to 100% for IgM, and the combined specificity ranged from 57.5% to 100%. For 2 assays that measure total Ig, sensitivity was 96.7% and 100%.

Conclusion
This program completed over 50 performance evaluations with well-characterized PEVs. Results have been used to inform FDA regulatory decisions and are publicly available on FDA’s website.

Disclosures
Cristina Cassetti, PhD, Nothing to disclose
Reproductive phasiRNA loci and DICER-LIKE5, but not microRNA loci, diversified in monocotyledonous plants
Authors: Patel Parth , Mathioni Sandra M , Hammond Reza , Harkess Alex E , Kakrana Atul , Arikit Siwaret , Dusia Ayush , Meyers Blake C 
Published: January 2021

Abstract
In monocots other than maize (Zea mays) and rice (Oryza sativa), the repertoire and diversity of microRNAs (miRNAs) and the populations of phased, secondary, small interfering RNAs (phasiRNAs) are poorly characterized. To remedy this, we sequenced small RNAs (sRNA) from vegetative and dissected inflorescence tissue in 28 phylogenetically diverse monocots and from several early-diverging angiosperm lineages, as well as publicly available data from 10 additional monocot species. We annotated miRNAs, small interfering RNAs (siRNAs) and phasiRNAs across the monocot phylogeny, identifying miRNAs apparently lost or gained in the grasses relative to other monocot families, as well as a number of transfer RNA fragments misannotated as miRNAs. Using our miRNA database cleaned of these misannotations, we identified conservation at the 8th, 9th, 19th, and 3′-end positions that we hypothesize are signatures of selection for processing, targeting, or Argonaute sorting. We show that 21-nucleotide (nt) reproductive phasiRNAs are far more numerous in grass genomes than other monocots. Based on sequenced monocot genomes and transcriptomes, DICER-LIKE5, important to 24-nt phasiRNA biogenesis, likely originated via gene duplication before the diversification of the grasses. This curated database of phylogenetically diverse monocot miRNAs, siRNAs, and phasiRNAs represents a large collection of data that should facilitate continued exploration of sRNA diversification in flowering plants.