bluuebunny/crossref_metadata_2025_split huggingface dataset:
976. Clostridium difficile Colonization Molecular Epidemiology and Anti-toxin Serological Responses in Healthy Infants: A Prospective Cohort Study
Authors: Kociolek Larry , Kelly Ciaran P , Espinosa Robyn , Budz Maria , Balaji Aakash , Ozer Egon , Tanz Robert , Chen Xinhua , Gerding Dale N 
Published: November 2018

Abstract

Background
Infant C. difficile colonization is common, but the molecular epidemiology and immunologic consequences of colonization are poorly understood.

Methods
In this prospective cohort study of healthy infants, serial stools collected between 1–2 and 9–12 month olds were tested for glutamate dehydrogenase (detects nontoxigenic or toxigenic C. difficile [TCD]), tcdB PCR (detects TCD), and cultured for C. difficile. Isolates underwent whole genome sequencing and multilocus sequence typing (MLST). Clonal strains were identified by single nucleotide variant (SNV) analysis. TCD was confirmed by BLAST identification of tcdA/tcdB. Serum collected at 9–12 month olds underwent ELISA for measurement of IgA, IgG, and IgM against TCD toxins A and B. For comparison, anti-toxin IgG was measured in cord blood of 50 consecutive full-term deliveries (unrelated to study infants). Arbitrary ELISA units were compared by Wilcoxon rank-sum test.

Results
Among 32 infants, 16 (50%) had at least one TCD+ stool, 12 of whom were colonized at least 1 m prior to serology measurements (Figures 1 and 2). A variety of STs were identified, and evidence of putative in-home (enrolled siblings) and outpatient clinic transmission was identified (Figure 3). Infants with TCD colonization had significantly greater levels of anti-toxin IgA and IgG compared with non-colonized infants and IgG compared with unrelated cord blood (Table 1).

Conclusion
Infant C. difficile colonization is a dynamic process with variable strain types and duration. Outpatient clinics may be a C. difficile reservoir for some patients. TCD colonization is associated with a humoral immune response against toxins A and B, but whether natural TCD immunization protects against CDI later in life requires further investigation.

Disclosures
L. Kociolek, Alere/Techlab: Investigator, Research support. C. P. Kelly, Actelion: Consultant, Consulting fee. Artugen: Consultant, Consulting fee. Facile: Consultant, Consulting fee. GSK: Consultant, Consulting fee. MSD: Consultant, Consulting fee. Seres: Consultant, Consulting fee. Summit: Consultant, Consulting fee. Vedanta: Consultant, Consulting fee. D. N. Gerding, Merck: Scientific Advisor, Consulting fee. Actelion: Scientific Advisor, Consulting fee. DaVolterra: Scientific Advisor, Consulting fee. Summit: Scientific Advisor, Consulting fee. Rebiotix: Medical Officer and Scientific Advisor, Consulting fee. Pfizer: Consultant, Consulting fee. MGB Pharma: Consultant, Consulting fee. sanofi pasteur: Consultant, Consulting fee. Seres: Investigator, Research grant. CDC: Investigator, Research grant. US Dept VA: Investigator, Research grant. Treatment/Prevention of C. difficile: Patent Holder, no license or royalties.
1629. Targeted Antimicrobial Use Admission Provides an Actionable Denominator for Antimicrobial Stewardship Programs Evaluating Inpatient Length of Therapy
Authors: Dyer April , Ashley Elizabeth Dodds , Davis Angelina , Johnson Melissa , Jones Travis , Moehring Rebekah W 
Published: November 2018

Abstract

Background
Actionable, easy to interpret antibiotic use (AU) metrics provide antimicrobial stewardship programs (ASPs) with clear targets. Current aggregate AU metrics lack the ability to discriminate between long courses in a limited number of patients versus short courses in a large number of patients.

Methods
We developed a novel AU denominator termed “targeted antimicrobial use admission,” defined as an inpatient admission in which a selected agent or group of agents was administered. When used with length of therapy (LOT), it provides the average number of days patients receive the targeted agent(s) during inpatient hospital admissions. To demonstrate the added utility of this metric, we used descriptive statistics to compare it to LOT, LOT/1,000 patient days, LOT/1,000 admissions, and LOT/admission to quantify intravenous (IV) vancomycin use among 25 hospitals in the Duke Antimicrobial Stewardship Outreach Network (DASON) for calendar year 2017. The metric was also used to compare hospitals to one another and track durations at an example hospital over time.

Results
Total LOT included 128,680 days of IV vancomycin (table). LOT/targeted antimicrobial use admission is the only metric that allows programs to quickly assess agent durations.

Conclusion
Stewardship programs seeking to shorten durations of therapy can track this metric over time to determine the impact of their ASP efforts (Figure 1). The metric can also be used to compare average durations of IV vancomycin by hospital to determine when and if agent-focused audit and feedback or antibiotic timeouts may be useful (Figure 2). The network mean provides a target for agent-specific de-escalations, in days, for facilities with longer durations. LOT/targeted antimicrobial use admission provides an actionable metric for quantifying antimicrobial durations. This metric is easy to interpret and can feasibly be captured through the electronic prescribing record to aid in selecting ASP strategy.

Disclosures
All authors: No reported disclosures.
1634. A 9-Point Risk Assessment for Patients Who Inject Drugs Requiring Intravenous Antibiotics May Allow Health Systems to Focus Inpatient Resources on Those at Greatest Risk of Ongoing Drug Use
Authors: Eaton Ellen , Mathews Ronald , Lane Peter S , Paddock Cayce S , Rodriguez J Martin , Taylor Benjamin B , Saag Michael , Kilgore Meredith , Lee Rachael 
Published: November 2018

Abstract

Background
We implemented an Intravenous Antibiotics and Addiction Team (IVAT) intervention to identify hospitalized persons with a history of injection drug use (IDU) that are safe for discharge with IV antibiotics based on a 9-point risk assessment. IVAT has been shown to reduce average length of stay (ALOS) without increasing readmissions. We analyzed the cost savings of the IVAT to the health system.

Methods
PWID at the University of Alabama at Birmingham (UAB) hospital with indications for prolonged IV antibiotics received IVAT to determine risk of continued IDU. “Low-risk” patients were discharged for outpatient antibiotics and addiction care; others continued inpatient antibiotics, group therapy, opioid agonist therapy (if applicable), and weekly assessment for discharge readiness. Cost of care was defined by direct costs and was obtained by querying financial accounts.

Results
A total of 37 pre-IVAT and 111 post-IVAT admissions (including 25 “low risk”) met study criteria. IVAT reduced ALOS by 20 days. Total direct costs per admission in the post-IVAT period were 33% lower: $26,014 versus $38,716 (Table 1). Because ALOS at UAB for all patients is 6.58 days, a 20-day ALOS reduction following IVAT creates capacity for an additional 333 patients (n = 20/6.58 × 111).

Conclusion
IVAT for PWID allows health systems to focus inpatient resources on those at greatest risk of ongoing IVDU, creates additional inpatient capacity, and may cut hospital direct costs by one-third.

Disclosures
J. M. Rodriguez, finch: Research Contractor, Research support. seres: Research Contractor, Research support.
1636. Variation in Clinical Practice Patterns Among Infectious Diseases Faculty at a Large Academic Institution
Authors: Phadke Varun K , Spicer Jennifer O 
Published: November 2018

Abstract

Background
Clinical practice patterns vary between providers, but few studies have examined this variation among infectious disease (ID) physicians. Characterizing these differences in practice can help identify areas where targeted educational interventions or further research are needed to improve clinical decision-making. We describe a faculty survey conducted at our institution designed to identify clinical practice variation within a large academic ID division.

Methods
In January 2017, an electronic survey was distributed to all clinical ID faculty at our institution. The survey collected baseline demographic information as well as responses to 28 common clinical dilemmas encountered in routine practice. Descriptive statistics were performed.

Results
Twenty-four (44%) of 54 active clinical ID faculty (12 assistant professors, 6 associate professors, and 6 professors) completed the survey. Examples of clinical dilemmas with &gt;80% agreement among faculty included: (1) S. aureus bacteremia should be a mandatory ID consult (88%) and (2) lumbar puncture should be performed for all patients with suspected ocular syphilis (88%). The majority of clinical dilemmas had less than 80% agreement, and these spanned the range of routine ID practice. Examples included: (1) use of ceftriaxone for outpatient antibiotic therapy for nonbacteremic invasive methicillin-susceptible S. aureus infections (58% agree), (2) length of treatment for guideline-defined uncomplicated S. aureus bacteremia (50% 2 weeks, 50% 4 weeks), (3) use of fixed-dose dolutegravir/abacavir/lamivudine as a single-drug regimen for an HIV-infected patient with an M184V mutation (42% agree), and (4) benefit of routine anal Pap smears among HIV-infected men who have sex with men (50% agree).

Conclusion
Practice patterns vary between ID physicians within our institution, particularly for clinical dilemmas for which there is insufficient or conflicting published data. Further studies to examine practice pattern variation among ID physicians across institutions and geographic regions could identify areas where further research or educational interventions are needed to enhance clinical care.

Disclosures
All authors: No reported disclosures.
1640. Toward New Anti-Biofilm Therapies: High Mobility Group Box 1 (HMGB1) Protein and Its Structural Variants Can Be Used to Disrupt Bacterial Biofilms (BBs)
Authors: Katragkou Aspasia , Warren Lauren , Buzzo John , Goodman Steven 
Published: November 2018

Abstract

Background
BB-related infections are a major public health problem, as they are notoriously refractory to current treatments. One of the defining characteristics of BBs is the extracellular polymeric substance (EPS). Extracellular DNA and the bacterial DNABII family of proteins are key components of EPS and are crucial for BBs structural integrity. It is known that targeting DNABII proteins disrupts BBs. We hypothesized that HMGB1, a DNA-binding eukaryotic protein, could affect BBs as it binds to the same DNA structures as the DNABII proteins. HMGB1 is comprised of 3 domains, A Box, B Box, and C tail, all of which have different functions. We aimed to determine in vitro the effects of HMGB1 and its individual domains against BBs.

Methods
Klebsiella pneumoniae (KP), a common cause of nosocomial infections, was used for all BBs disruption assays. Human recombinant full-length HMGB1 (rHMGB1; 1–215), a C45S mutation variant (mHMGB1) and the HMGB1 domains A Box (1–89), B Box (90–176), AB Boxes (1–176), B-linker Box (80–179), and B-linker Box C106S were expressed (in E. coli) and purified to &gt;95%. To evaluate the effect of rHMGB1 and the various domains on established BBs, each protein species (200 nM) was added to preformed BBs at 24 hours. At 40 hours the BBs were washed, stained with LIVE/DEAD®, visualized via confocal laser scanning microscopy and images were analyzed by COMSTAT to calculate average thickness and biomass.

Results
Exogenous rHMGB1 and its individual domains, with the exception of A Box caused a significant reduction (P &lt; 0.05) in average thickness (AT) and biomass (BM) of KP biofilms when compared with untreated KP biofilms (% reduction mean ± SE in AT: 44% ± 0.33, 75% ± 0.04, 63% ± 0.1, 77% ± 0.03, 64% ± 0.08, 54% ± 0.15 and in BM: 61% ± 0.01, 80% ± 0.01, 68% ± 0.02, 67% ± 0.01, 73% ± 0.02, 56% ± 0.02 induced by rHMGB1, mHMGB1, B-Box, B-linker Box, AB Boxes, and B-linker Box C106S, respectively).

Conclusion
Full-length recombinant HMGB1 was able to significantly disrupt established KP biofilms as were all truncated HMGB1 forms containing the B Box domain and could potentially be used as a therapeutic treatment for BB-related infections.

Disclosures
J. Buzzo, ProclaRx: Collaborator, Research support. S. Goodman, ProclaRx: Collaborator and Scientific Advisor, Research support.
1663. Marked Improvement in Pandemic H1N1 Component Shedding and Immunogenicity in 2017–2018 Russian-Backbone Live Attenuated Influenza Vaccine (LAIV) in Gambian Children
Authors: Lindsey Benjamin , Jankey Jagne , Armitage Edwin , Jeffries David , Mohammed Nuredin , Drammeh Sainabou , Senghore Elina , Sallah Hadi , Tregoning John , Hoschler Katja , Dong Tao , Clarke Ed , Kampmann Beate , De Silva Thushan 
Published: November 2018

Abstract

Background
Recent observational studies in the United States have reported reduced effectiveness of the Ann Arbor-backbone live attenuated influenza vaccine (LAIV), coinciding with emergence of 2009 pandemic H1N1 (pH1N1). A recent RCT in Senegal of the Russian-backbone LAIV also showed no efficacy, with pH1N1 the predominant vaccine-matched strain circulating during the study. The reasons for this reduced effectiveness and efficacy are unclear but may involve pre-existing immunity or pH1N1 virus-specific factors. We explore these underlying reasons through an LAIV immunogenicity study in Gambian children across 2 influenza seasons.

Methods
Gambian children aged 24–59 months (n = 118) were given 2016–17 northern hemisphere Russian-backbone trivalent LAIV. Vaccine shedding, haemagglutinin inhibition (HAI) titre, influenza-specific T-cell responses, and mucosal IgA were measured using RT-PCR, HAI assay, flow cytometry, and ELISA, respectively. The following year, a further 127 children were given 2017–2018 formulation LAIV, where the pH1N1 strain was updated.

Results
In 2016–2017, significantly less pH1N1 shedding (13.6% children) was seen compared with H3N2 (45.8%) and B/Victoria (80.5%). Similarly, poor pH1N1-specific HAI (5.1% seroconversion), mucosal IgA (18.6% responders) and T-cell responses (&lt;10% responses to pH1N1 HA) were seen, whereas significantly greater responses in ≥1 immune compartments were seen to H3N2 and B/Victoria. pH1N1 shedding was not related to pre-existing immunity in 2016–2017. Vaccination with 2017–2018 LAIV showed improvement in pH1N1 shedding with no significant difference between strains: 67.7%, 63.2%, and 68.4% children shedding pH1N1, H3N2, and B/Victoria at day 2 post-LAIV (see Figure 1). This was matched by enhanced pH1N1 HA-specific T-cell responses, with 47.1% children showing a CD4+IFNg+ and 54.4% a CD4+IL2+ response (see Figure 2). HAI and mucosal IgA data for 2017–2018 are currently being generated and will be presented, as well as key interactions between the parameters measured.

Conclusion
Our data suggest that poor pH1N1 A/California strain replication in vivo may explain recent suboptimal LAIV performance and suggest that an improvement can be expected with new pH1N1 strains included in current LAIV formulations.

Disclosures
All authors: No reported disclosures.
1716. Results of the Respiratory Protection Effectiveness Clinical Trial (ResPECT)
Authors: Radonovich Lewis , Simberkoff Michael S , Bessesen Mary , Brown Alexandria C , Cummings Derek , Gaydos Charlotte , Los Jenna , Krosche Amanda , Gibert Cynthia , Gorse Geoffrey , Nyquist Ann-Christine , Reich Nicholas , Rodriguez-Barradas Maria , Price Connie , Perl Trish 
Published: November 2018

Abstract
Results of the Respiratory Protection Effectiveness Clinical Trial (ResPECT)

Background
Respiratory protection (RP) for healthcare personnel (HCP) is controversial and clinical studies are inconclusive about the effectiveness of N95 respirators (N95) and medical masks (MM) for protecting HCP from workplace viral respiratory infections and illnesses (VRII).

Methods
We conducted a cluster-randomized, investigator-blinded, multisite effectiveness study comparing N95 to MM in geographically diverse, high exposure outpatient settings between 2011 and 2016. Each year during VRII season, participants wore assigned devices when within 6 feet of patients with known or suspected respiratory illness. Respiratory swabs were collected from symptomatic and asymptomatic participants. Diaries detailed VRII exposures, influenza vaccination, adherence to RP and hand hygiene, and manifestations of illness. The primary and secondary outcomes were the incidence of laboratory-confirmed influenza (LCI) using polymerase chain reaction (PCR) and hemagglutinin inhibition assays (HAI), and acute respiratory illness (ARI), influenza-like illness (ILI), laboratory-confirmed respiratory illness (LCRI), and laboratory-detected respiratory infection (LDRI) (figure). Intervention protective effects were estimated using unadjusted odds and incidence rate ratios.

Results
5,180 HCP seasons enrolled and randomized (2,243 to N95 and 2,446 to MM), with 4,689 (91%) completing the study. In the intention-to-treat cohort (ITT), among participants in the N95 and MM groups, respectively, 207 (8.2%) and 193 (7.2%) were diagnosed with LCI (odds ratio [OR] 1.14, 95% confidence interval [CI] 0.93–1.40); 1,556 (61.9%) and 1711 (64.1%) were diagnosed with ARI (relative risk (RR) 0.99, CI 0.92–1.06); 128 (5.1%) and 166 (6.2%) were diagnosed with ILI (RR 0.87, CI 0.68–1.10), 371 (14.8%) and 417 (15.6%) were diagnosed with LCRI (RR 0.97, CI 0.84–1.12); and 679 (27.0%) and 745 (27.9%) were diagnosed with LDRI (RR 0.99, CI 0.89–1.09). The adjusted ITT and per-protocol analyses yielded similar results.

Conclusion
In this outpatient-based, cluster-randomized, controlled trial, neither N95 nor MM resulted in superior protection from LCI or VRII.

Disclosures
C. Gaydos, BioFire: Consultant, Consulting fee. Cepheid: Speaker’s Bureau, Speaker honorarium. Becton Dickinson: Speaker’s Bureau, Speaker honorarium.
1728. Effectiveness and Healthcare Personnel (HCP) Perceptions of a Multi-Site Personal Protective Equipment (PPE) Free Zone Intervention
Authors: Visnovsky Lindsay , Mulvey Diane , Zhang Yue , Leecaster Molly , Donskey Curtis J , Krein Sarah L , Safdar Nasia , Alhmidi Heba , Barko Lauren , Haroldsen Candace , Ide Emma , Nevers McKenna , Shaughnessy Catherine , Stratford Kristina , Drews Frank , Samore Matthew , Mayer Jeanmarie 
Published: November 2018

Abstract

Background
CDC provides guidelines for using contact precautions (CP) when caring for patients with antibiotic-resistant bacteria or Clostridium difficile. However, HCP frequently report discomfort, difficulty of use, and interrupted workflow with CP. Modifying CP guidelines to balance these issues requires testing to assess benefits and maintenance of safe practices. A promising approach using a “PPE Free Zone” strategy within rooms of patients in CP has not been well-studied.

Methods
The PPE Free Zone comprised a 3–6 foot area inside door thresholds of CP patient rooms denoted by red tape placed on the floor. Within the zone, HCP were not required to don PPE. HCP were considered compliant if they performed hand hygiene (HH) and donned appropriate PPE before crossing the zone. Observers at 6 acute care facilities (ACF) were trained on observing HCP HH and use of PPE with CP. Observations were made before and after implementation of a PPE Free Zone. Intervention ACF conducted observations on 8 intervention units and 6 nonintervention units. Models of overall compliance and entry HH compliance were constructed using a generalized linear-mixed effects model with a logistic link function. Pre-intervention observations from all 6 ACF and intervention phase observations from the 3 intervention ACF were used in models.

Results
We observed 4,510 room entries. HH adherence declined over time in both intervention and control units but declined less among intervention units from pre to post intervention (β: 0.71, P = 0.007, Figure 1). Stratified by precautions type, the effect of the PPE Free Zone on HH was only significant for rooms in enteric precautions (P &lt; 0.001). Compliance with PPE use was not significantly different pre- versus postintervention (P = 0.133). When surveyed, HCP had positive views of the PPE Free Zone: 65% (n = 172) agreed or strongly agreed the zone facilitates communication with patients, permits checking on patients more frequently, and saves time [n = 169] (Figure 2).

Conclusion
Although HCP viewed the zone positively and it had a significant effect on HH in enteric precautions rooms, the zone did not improve PPE compliance. Future interventions in the ACF setting should consider the complex sociotechnical system factors influencing behavior change.

Disclosures
All authors: No reported disclosures.
1729. Effect of Glove Disinfection on Bacterial Contamination of Healthcare Worker Hands
Authors: Robinson Gwen , Kpadeh Zegbeh Z , Alserehi Haleema , Morgan Daniel , Harris Anthony D , Johnson J Kristie , Leekha Surbhi 
Published: November 2018

Abstract

Background
Disinfection of gloves and gowns was recommended to decrease healthcare worker (HCW) self-contamination during doffing of gloves and gowns in the Ebola epidemic. To understand the potential role of this practice in preventing bacterial transmission, we examined the effect of disinfectants on bacterial contamination of HCW hands following glove removal.

Methods
A laboratory simulation study was conducted using methicillin-susceptible Staphylococcus aureus and antibiotic-sensitive Klebsiella pneumoniae among volunteer HCWs (n = 10 per organism). For each experiment, the volunteer donned 2 pairs of gloves with the “under glove” simulating HCW hands and “top glove” simulating actual glove use in the clinical setting. The top-glove was inoculated with 108 CFU bacteria for each step. Top gloves were sampled directly after inoculation (Arm A), and after disinfection with alcohol gel, bleach wipes, and quaternary ammonium (quat) wipes, in separate steps (Arm B). Under gloves were sampled after top glove removal without disinfection (Arm C), and top glove removal post disinfection (Arm D). Quantitative bacterial load reduction was compared for glove use (Arm C − Arm A), and for disinfectant use in addition to glove use (Arm D − Arm C). Qualitative detection of any bacterial load (present/absent) on under glove in the setting of disinfection prior to top glove removal was also assessed.

Results
Of 108 CFU inoculated, the median recovery was 1.2 × 104 CFU (both bacteria combined). After glove removal (no disinfection), the median recovery from the under glove was 2.7 × 102 CFU, for a reduction of 98% (1.6 log) in bacterial load. After top glove disinfection and removal, the median bacterial recovery from the under glove was 1.4 × 102, 0, and 0 CFU for alcohol, quat, and bleach (47% or 0.3 log reduction for alcohol; 99% or 2 log reduction for quat and bleach) (Figure 1). Regardless of quantity, bacteria were recovered from under gloves even after top glove disinfection in 70%, 40%, and 35% cases for alcohol, quat, and bleach, respectively (Figure 2).

Conclusion
Glove disinfection prior to glove removal is effective at reducing bacterial contamination of HCW hands. However, despite disinfection, some level of hand contamination occurs frequently.

Disclosures
J. K. Johnson, Q-Linea: Investigator, Research grant. Applied Biocode: Investigator, Research grant