bluuebunny/crossref_metadata_2025_split huggingface dataset:
1630. Antibiotics Prescribed for Infection Prophylaxis Prior to Dental Procedures Are Frequently Unnecessary in the United States
Authors: Suda Kj , Adimadhyam Sruthi , Calip Greg , Rowan Susan , Gross Alan E , Perez Rose , Hershow Ronald , McGregor Jessina C , Evans Charlesnika 
Published: November 2018

Abstract

Background
Antibiotics are recommended prior to certain dental procedures (“antibiotic prophylaxis”) in patients with select comorbidities to prevent serious distant site infections. Our objective was to assess the appropriateness of antibiotic prophylaxis by dentists using Truven, a national integrated medical, dental, and prescription (Rx) claims database of 350 commercial plans.

Methods
Cross-sectional study of 8.7 million adult dental visits in 2015. Antibiotic prophylaxis was defined as Rx with &lt;3 days supply dispensed within 7 days before a dental visit. Medical diagnoses were evaluated in medical/hospital claims from 2009 to 2015. Patients with hospitalizations and infection diagnoses 14 days prior to the Rx date were excluded. Appropriate antibiotic prophylaxis was defined as a dental visit with a procedure that manipulated the gingiva/tooth periapex in patients with an appropriate cardiac diagnosis. Chi Square and logistic regression were applied.

Results
In 2015, 30,726 antibiotics were prescribed for dental infection prophylaxis for 21,986 patients (mean age=58.6 + 15.0 years; 55.9% female). Amoxicillin (68.5%) and clindamycin (14.7%) were most common. 29,879 dental visits were associated with 69,639 dental codes ([CDTs]; range 1–14 CDTs/visit). Most dental visits were diagnostic (65.9% of visits with &gt;1 diagnostic CDT), preventative (53.0%), and restorative (11.2%). 98.4% of dental visits had an appropriate CDT for antibiotic prophylaxis. Comorbidities include orthopedic implants (45.4%) and cardiac diagnoses at the highest risk of infective endocarditis (22.2%). Per guidelines, 78.0% of dental visits with antibiotic prophylaxis were inappropriate. Amoxicillin was more likely to be inappropriate than other agents (OR=1.65; 95% CI: 1.55–1.76). Orthopedic implants (OR=3.35; 95% CI: 3.14–3.56), tooth implant procedures (OR=3.30; 95% CI: 2.48–4.39), females (OR=1.35; 95% CI: 1.27–1.43) and the western US (OR=1.22; 95% CI: 1.09–1.36) were associated with inappropriate prescribing.

Conclusion
Antibiotic prophylaxis is prescribed for indicated dental procedures, but is not appropriately limited to patients with cardiac diagnoses per guidelines. Implementing antimicrobial stewardship efforts in dental practices may be an opportunity to improve antibiotic prescribing for infection prophylaxis.

Disclosures
J. C. McGregor, Merck: Grant Investigator, Research grant.
1631. Made to Measure: Development of a Scoring Tool to Customize Antimicrobial Stewardship Goals Across a Large Health System
Authors: Logan Andrea Y , Williamson Julie E , Jarrett Steven , Davidson Lisa E 
Published: November 2018

Abstract

Background
The 2015 National Action Plan for Combating Antimicrobial Resistance called for a 20% decrease in antibiotic use among inpatients. Atrium Health (AH), formerly Carolinas HealthCare System, established reductions in antibiotic use (determined by days of therapy [DOT] per 1,000 patient days [PD]) as a yearly system-wide quality goal since 2016. Hospitals in the AH inpatient network vary by size, scope, and antimicrobial stewardship program (ASP) maturity. Prior to our third year, we recognized the need to develop an objective method for determining antibiotic use reduction goals (AURGs); understanding that as ASPs mature, opportunities for reduction stabilize over time and may eventually plateau with consistent ASP. We sought to develop a tool that would better identify hospitals in need of aggressive AURGs.

Methods
A scoring tool was developed to assess ASP implementation and metric achievement at individual hospitals to determine AURGs. Tool components were developed from ASP best practices and consensus among a multi-disciplinary team. The tool yields a maximal score of 41.5 points, with higher scores corresponding to more established ASPs who require less aggressive AURGs. An additional 6 points could be earned for tracked intervention data.
Figure 1. Scoring Tool Components

The tool was applied and a score calculated for each of 27 hospitals. Achieved score placed each hospital into one of 4 AURG ranges: maintain, 1–2.5%, 2.5–5%, and 5–7.5% of DOT/1000 PD. Goals were determined in relation to the median and 75th percentile scores. A minimum score of 39.5, representing full implementation of ASP score components, was required for a maintenance goal.

Results
Scores ranged from 3 to 34.5 points across facilities (median 27.5; 75th percentile 31). Twelve facilities scored below 27.5 points, 10 hospitals between 27.5 and 31 points, and 5 facilities between 31 and 39.5 points corresponding to 5–7.5%, 2.5–5% and 1–2.5% AURGs, respectively.
Figure 2. Facility Scores and AURGs

Conclusion
Scores and corresponding AURGs were generally well accepted by stakeholders at facilities within the AH network. Next steps include examining the feasibility of achieving AURGs and obtaining feedback from facilities to refine the tool. The tool will also be applied to other healthcare networks to assess external validity.

Disclosures
All authors: No reported disclosures.
1635. Do Persons With Opioid Use Disorder and Injection-Related Infections Really Need Prolonged Hospitalizations to Complete Intravenous Antibiotic Therapy?
Authors: Fanucchi Laura , Walsh Sharon , Thornton Alice , Nuzzo Paul , Lofwall Michelle 
Published: November 2018

Abstract

Background
Persons with opioid use disorder (OUD) hospitalized with severe, injection-related infections (e.g., endocarditis) often remain inpatient to complete intravenous (IV) antibiotics due to assumptions that, if outpatient, patients will inject drugs into the IV catheter and will fail to complete prescribed antibiotic regimens. No evidence supports these assumptions, and unfortunately, the inpatient stay infrequently includes OUD pharmacotherapy. The aim is to determine whether inpatients with OUD and injection-related infections can be safely discharged to complete antibiotics through a IV catheter in the context of comprehensive outpatient OUD treatment including buprenorphine.

Methods
Pilot proof-of-concept, randomized study enrolling hospitalized adults with OUD and severe injection-related infections. Participants are provided inpatient buprenorphine treatment with counseling and randomized (1:1) to usual care (UC) [completing IV antibiotics inpatient] or to early discharge (ED) [completing IV antibiotics outpatient]. Both groups receive 12 weeks of comprehensive OUD treatment with buprenorphine after discharge.

Results
Seventy-six patients screened, 20 met eligibility criteria, provided informed consent, and randomized; 10 to UC and 10 to ED. Similar baseline characteristics; 90% in UC with endocarditis and 100% in ED. Length of stay, UC: 45.9 days (SD ±7.8), ED 22.7 (SD ±7.5) (P &lt; 0.001). Ten in UC and 9 in ED completed recommended IV antibiotics, one in ED group is still receiving antibiotics; ED finished 19.8 days (SD ±11.7) IV antibiotics outpatient. Self-reported illicit opioid use 30 days before hospitalization compared with 12-week outpatient phase decreased in both groups (P = 0.009); no significant difference between groups (P = 0.141) (Figure 1).

Conclusion
Early results suggest patients with OUD and complex injection-related infections may be safely discharged to complete IV antibiotics via indwelling catheters if comprehensive OUD treatment with buprenorphine is started while inpatient and continued after discharge. Importantly, while prolonged inpatient care is common practice, viewed as protective but extremely costly, these data suggest that comprehensive outpatient care is feasible and may be equi-effective.

Disclosures
All authors: No reported disclosures.
1642. Safety and Efficacy of Bacteriophage Therapy: Analysis of Clinical Case Series Data
Authors: Aslam Saima , Gilbey Timothy , Maddocks Susan , Morales Sandra , Lehman Susan , Branston Steven , Fabijan Aleksandra Petrovic , Furr Carrie-Lynn Langlais , Rosas Francisco , Bilinsky Igor , Grint Paul , Schooley Robert T , Iredell Jonathan 
Published: November 2018

Abstract

Background
Bacteriophage therapy (BT) is a re-emerging strategy to treat antibiotic-resistant infections. Here, we describe our initial experience with intravenous (IV) and inhaled BT to treat life-threatening Staphylococcus aureus and Pseudomonas aeruginosa infections not responding to antibiotic therapy. Emergency Investigational New Drug application approvals (United States) or Special Access Scheme Category A notifications (Australia) and informed consent from the patients were obtained.

Methods
Patients were treated with AB-SA01 (3-phage product targeting S. aureus) and AB-PA01 (4-phage product targeting P. aeruginosa) produced in a Good Manufacturing Practice-certified facility. Pre- and posttreatment bacterial isolates were tested for phage susceptibility during BT. In all cases, concomitant antibiotics were continued. Safety was assessed clinically and using laboratory parameters with up to 90 days of follow-up. Samples to assess bacterial loads, bacteriophage kinetics in blood, and immune responses to phage were collected.

Results
As of April 2018, 8 patients were treated with BT; 5 with AB-SA01 (bacteremia, n = 4; endocarditis, n = 1) and 3 with AB-PA01 (lung infection, n = 3). Median duration of BT was 14 days and treated patients received over 90 IV doses of AB-SA01 (3 × 109 PFU/dose) and over 490 IV and nebulized doses of AB-PA01 (4 × 109 PFU/dose). BT was well tolerated, with no treatment-related adverse events. Clinical treatment success was documented in 75% of patients. Isolates collected during therapy showed ongoing susceptibility to the BT products with changes in sensitivity to the individual phage components observed in some cases. Bacteriophage kinetics revealed bloodstream clearance within a few hours after IV infusion, with an inferred initial bacteria:bacteriophage ratio of ~200 for the bacteremia patients.

Conclusion
BT was well tolerated as an adjunct to antibiotics, with several examples presented of microbiological eradication and improvement of objective clinical criteria. BT appears to be a safe adjunct to antibiotic therapy in life-threatening S. aureus and P. aeruginosa infections and is a promising candidate for controlled clinical trials.

Disclosures
S. Morales, AmpliPhi Biosciences: Employee, Salary. S. Lehman, AmpliPhi Biosciences: Employee, Salary. S. Branston, AmpliPhi Biosciences: Employee, Salary. A. Petrovic Fabijan, AmpliPhi Biosciences: Collaborator, Research support. C. L. Langlais Furr, AmpliPhi Biosciences: Employee, Salary. F. Rosas, AmpliPhi Biosciences: Employee, Salary. I. Bilinsky, AmpliPhi Biosciences: Employee and Shareholder, Salary. P. Grint, AmpliPhi Biosciences: Board Member, Employee and Shareholder, Salary. J. Iredell, AmpliPhi Biosciences: Collaborator, Research support.
1647. Real-Time Metagenomic Sequencing Reveals Discrete Transmission Clusters Within a Hospital-Associated Norovirus Outbreak
Authors: Casto Amanda , Adler Amanda , Makhsous Negar , Qin Xuan , Crawford Kristen , Jerome Keith , Zerr Danielle , Greninger Alex 
Published: November 2018

Abstract

Background
Norovirus is the most common cause of acute gastroenteritis in the United States and a major challenge for infection control efforts. The high burden of norovirus in most communities and health care systems makes it difficult to discern viral transmission patterns using traditional epidemiological approaches alone.

Methods
We performed real-time metagenomic sequencing of norovirus isolates from an outbreak among inpatients at Seattle Children’s Hospital (SCH). We also sequenced isolates from norovirus cases within the larger University of Washington (UW) Medical System that occurred during and after the outbreak.

Results
Our data showed that the month-long outbreak at SCH was actually characterized by 3 distinct concurrent transmission clusters contained within 3 different hospital units. We were able to report this information to the infection control team at SCH while the outbreak was still in progress. The virus responsible for one of these 3 clusters was genetically stable over a period of 4.5 weeks suggesting serial transmissions from a contaminated fomite, rather than patient to patient transmission. After cases meeting the epidemiological definition for hospital-acquired had ceased, we demonstrated that the virus from one of the 3 outbreak clusters continued to be transmitted to other patients within the SCH medical system. Finally, we showed that one of the patients who acquired norovirus during the outbreak developed a chronic infection with viral shedding documented up until the time of the patient’s death, 8 months after the outbreak.

Conclusion
These results demonstrate the value of using metagenomics as an adjunct to traditional epidemiologic techniques in the setting of a hospital-associated norovirus outbreak. Real-time metagenomic sequencing elucidated viral transmission patterns within the outbreak while it was still in progress and follow-up sequencing revealed further infections due to an outbreak-associated viral strain even after the outbreak was thought to be over. Given this potential, metagenomic analyses represent an invaluable, largely untapped resource for improving our understanding of and reducing adverse effects from viral outbreaks.

Disclosures
All authors: No reported disclosures.
1719. Pharmacokinetics (PK) of Oritavancin in Children: The ORKIDS Trial
Authors: Bradley John , Arrieta Antonio , Bokesch Paula , Fusaro Karen , Griffith David C , Loutit Jeffrey S 
Published: November 2018

Abstract

Background
Oritavancin (ORI) is a lipoglycopeptide antibiotic approved in adults as a single 1,200 mg intravenous (IV) dose for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive organisms, including methicillin-resistant Staphylococcus aureus. The objective in children is to achieve a PK profile that is similar to that attained in adults. PK and safety data from the first 3 age-specified cohorts are presented.

Methods
The ORKIDS trial is a Phase 1 open-label, sequential, dose-finding study evaluating the PK, safety and tolerability of a single-dose 15 mg/kg (max 1,200 mg) IV infusion of oritavancin in children under 18 years. The first 3 age cohorts (12 to &lt;18 years, 6 to &lt;12 years, 2 to &lt; 6 years) with 8 subjects in each cohort have completed the study. Subjects were required to have a suspected or confirmed Gram-positive bacterial infection for which they received standard-of-care antibiotic therapy. Following a single dose of ORI, PK samples were obtained at 3, 4, 9, 24, 48, 72, and 336 hours after the start of the 3-hour infusion. Plasma concentrations were analyzed by noncompartmental Methods. Subjects were evaluated for safety through Day 60. An independent data safety monitoring board evaluated the safety and PK data of each cohort prior to dosing the subsequent cohort.

Results
PK in children compared with adult data from the SOLO Phase 3 ABSSSI studies (Table 1).

Conclusion
In subjects 6 to &lt;18 years, a single 15 mg/kg dose of ORI appears to be well tolerated and provides a PK profile similar to a single 1,200 mg dose in adults. Mean AUC0-inf of 1,963 h μg/mL in subjects 2 to &lt;6 years is lower than the targeted exposure range in adults. A higher dose of ORI is currently being studied in this cohort.

Disclosures
J. Bradley, Melinta Therapeutics: Investigator, Research support. A. Arrieta, Melinta Therapeutics: Investigator, Research support. P. Bokesch, Melinta Therapeutics: Consultant, Consulting fee. K. Fusaro, Melinta Therapeutics: Employee, Salary. D. C. Griffith, Melinta Therapeutics: Consultant, Consulting fee. J. S. Loutit, Melinta Therapeutics: Consultant, Consulting fee.
1720. Regional Differences in Trends of Hospitalizations Associated With Tick-Borne Diseases in the United States, 2009–2014
Authors: Adjemian Jennifer , Lai Yi Ling , Ricotta Emily , Prevots D Rebecca 
Published: November 2018

Abstract

Background
Tick-borne diseases are increasing in incidence in the United States; however, limited data exist on regional trends of associated hospitalizations. Using a nationally distributed dataset of US hospital-based medical records, we aimed to assess trends in incidence of hospitalizations from tick-borne disease by geographic region.

Methods
Data were examined from 156 US hospitals from 2009 to 2014 to identify hospitalizations with tick-borne disease. Cases were described and Poisson regression used to estimate the annual percent change (APC) and associated 95% confidence intervals (CI) in incidence by region over time.

Results
Overall, 2,543 hospitalized patients with tick-borne disease were identified (average annual incidence = 28.4 cases/100,000 hospitalized persons), including 1,613 (63%) with Lyme disease, 379 (15%) tick-borne fever, 293 (12%) ehrlichiosis, 93 (4%) babesiosis, 43 (2%) rickettsiosis, and 122 (4%) multiple tick-related diagnoses. Tick-borne diseases varied significantly by region, with Lyme disease more frequent in those residing in the Northeast (68%) than the South (57%) or West (42%) and tick-borne fever more common in the West (28%) vs. the South (18%), Midwest (14%), and Northeast (13%) (P &lt; 0.0001). Significant increases in tick-borne disease hospitalizations were identified across nearly all US regions, ranging from 15% per year in the South (95% CI=8–24%) to 45% per year in the West (34–58%), with the exception of the Northeast, where incidence declined by 6% per year (0.04–11%). Lyme disease hospitalizations showed similar trends, with the greatest increase in the South (APC = 53%, 95% CI = 33–76%) and a decrease in the Northeast (APC = 13%; 3%–23%). Hospitalizations with tick-borne fever increased in the Midwest (APC = 49%; 8–206%) and Northeast (APC = 18%; 4–34%); with ehrlichiosisincreased in the West (APC = 231%; 75–306%); and with babesiosis increased in the South (APC = 50%; 12–201%) and the Midwest (APC = 21%; 5–39%).

Conclusion
Incidence of hospitalizations from tick-borne disease is increasing throughout much of the nation, except in the Northeast where decreases in Lyme disease were observed. While hospitalizations with tick-borne diseases remain rare, the increases noted are substantial and may reflect rising incidence of these diseases within the represented states.

Disclosures
All authors: No reported disclosures.
1757. Using the Desirability of Outcome Ranking for Management of Antimicrobial Therapy (DOOR-MAT) to Assess Antibiotic Therapy Guided by Rapid Molecular Diagnostics (RMD) in Bloodstream Infection (BSI) Caused by Escherichia coli and Klebsiella pneumoniae
Authors: Wilson Brigid , Viau Roberto , Perez Federico , Jiang Yunyun , Fowler Vance G , Chambers Henry F , Kreiswirth Barry N , Bonomo Robert A , Evans Scott R ,   ARLG
Published: November 2018

Abstract

Background
In the setting of Escherichia coli and Klebsiella pneumoniae BSI, empiric antibiotic therapy is determined by clinical judgement and Gram stain (GS) of the positive blood culture bottle up to 2 days before antibiotic susceptibility test (AST) results become available. Within hours of GS, RMD can detect E. coli and K. pneumoniae and predict the pattern of susceptibility to β-lactams (BL) of differing spectrum. In this study, our objective was to compare “real-life” empiric therapy for E. coli and K. pneumoniae BSI administered between GS and AST results with simulated RMD-guided therapy.

Methods
We identified a subset of patients hospitalized within VHA between 2006 and 2015 who had a blood culture positive for E. coli or K. pneumoniae, and received empiric BLs between GS and AST Results. We further restricted the cohort to those with observed or implied AST results for 4 representative BLs: cefazolin, ceftriaxone, piperacillin–tazobactam, and imipenem. We extracted BL resistance patterns and, based on previously analyzed RMD performance on 195 E. coli and K. pneumoniae, we simulated RMD results for our cohort by resampling RMD results stratified by resistance pattern at the observed frequencies of resistance patterns in our clinical isolates. We simulated therapy guided by RMDs and compared with the observed empiric BLs using a DOOR-MAT score (Figure 1).

Results
A total of 36,531 BSI cases were identified. Of these, 9,981 E. coli and 4,545 K. pneumoniae met our inclusion criteria (Figure 2). Among these, susceptibility to all BLs occurred in 88% of cases; resistance to all BLs occurred in &lt;0.5%. The isolates previously analyzed using RMD included more resistant phenotypes (Figure 3). Empiric BLs were active in 98% of BSIs, with a mean DOOR-MAT score of 66.1 and 59% of cases classified as “moderate overtreatment.” Simulated RMD-guided BL therapy would be active in 95% of cases with a mean DOOR-MAT score of 91.4 (95% CI, 91.2–91.7), and 7% of cases would be classified as overtreatment.

Conclusion
In a large cohort of BSI patients where rates of BL resistance were low, we observed that empiric BL therapy, although highly effective, is of broader spectrum than necessary. RMD-guided therapy has the potential to reduce overtreatment without compromising effective therapy. DOOR-MAT provides a flexible framework for measuring appropriateness of therapy for BSI.

Disclosures
All authors: No reported disclosures.
1758. Impact of Accelerate Pheno™ Rapid Blood Culture Detection System on Laboratory and Clinical Outcomes in Bacteremic Patients
Authors: Dare Ryan , McCain Kelsey , Lusardi Katherine , Daniels Kay , Painter Jacob , Lakkad Mrinmayee , Emery Nicole , Rosenbaum Eric , Bariola J Ryan 
Published: November 2018

Abstract

Background
Molecular-based automated systems for the rapid diagnosis of bacterial infections have potential to improve patient care. The Accelerate Pheno™ blood culture detection system (ACCEL) is an FDA approved platform that allows for identification (ID) and antimicrobial susceptibility testing (AST) 8 hours following growth in routine culture.

Methods
This is a single-center retrospective chart review of bacteremic adult inpatients before and after implementation of ACCEL. Laboratory and clinical data were collected February–March 2018 (intervention) and compared with a January–April 2017 historical cohort (standard of care). Standard of care ID and AST were performed using VITEK® MS (MALDI-TOF MS) and VITEK®2, respectively. An active antimicrobial stewardship program was in place during both study periods. Patients with polymicrobial cultures, off-panel isolates, previous positive culture, or who were discharged prior to final AST report were excluded. Primary outcome was length of stay (LOS). Secondary outcomes were inpatient antibiotic duration of therapy (DOT) and time to optimal therapy (TTOT). Nonparametric unadjusted analyses were performed due to non-normal distributions. Statistics were performed using SAS 9.4.

Results
Of the 143 positive cultures performed on ACCEL during intervention, 118 (83%) were identified as on-panel organisms. Seventy-five (64%) of these 118 cultures and 79 (70%) of 113 reviewed standard of care cultures met inclusion criteria. Patient comorbidities (P = NS), MEWS severity score (P = 0.10), source of bacteremia (P = NS), and pathogen detected (P = 0.30) were similar between cohorts. Time from collection to ID (28.2 ± 12.7 hours vs. 53.8 ± 20.9 hours; P &lt; 0.001) and AST (31.9 ± 11 hours vs. 71.8 ± 20 hours; P &lt; 0.001) were shorter in the intervention arm.

Conclusion
Compared with standard of care, ACCEL shortens laboratory turn-around-time and improves clinical outcomes. The use of this system has resulted in decreased mean antibiotic DOT, TTOT, and LOS. Further studies are needed to verify these findings.

Disclosures
All authors: No reported disclosures.