bluuebunny/crossref_metadata_2025_split huggingface dataset:
2839. Efficacy, Pharmacokinetics (PK), and Safety Profile of Suvratoxumab (MEDI4893), a Staphylococcus aureus Alpha Toxin (AT)-Neutralizing Human Monoclonal Antibody in Mechanically Ventilated Patients in Intensive Care Units; Results of the Phase 2 SAATELLITE Study Conducted by the Public-Private COMBACTE Consortium
Authors: Francois Bruno , Sánchez Garcia Miguel , Eggimann Philippe , Dequin Pierre-Francois , Laterre Pierre-François , Huberlant Vincent , Viña Soria Lucia , Boulain Thierry , Bretonnière Cédric , Pugin Jerome , Trenado Álvarez José , Catalina Hernandez Padilla Ana , Coenjaerts Frank , Ali Omar , Shoemaker Kathryn , Ruzin Alexey , Pierre Vadryn , Wu Yuling , Colbert Susan , McCarthy Michael , Dubovsky Filip , S. Jafri Hasan 
Published: October 2019

Abstract

Background
Staphylococcus aureus (SA) pneumonia imposes significant morbidity and mortality in mechanically ventilated, intensive care unit (MV ICU) patients despite best clinical care. We assessed efficacy, PK, AT-neutralizing antibodies (AT NAbs), and safety of suvratoxumab (suvra) in MV ICU subjects in the placebo-controlled, randomized Phase 2 SAATELLITE study (NCT02296320; EudraCT 2014-001097-34).

Methods
Subjects with PCR-confirmed SA colonization of the lower respiratory tract were randomized to either a single intravenous infusion of 5,000 mg suvra (n = 96) or placebo (n = 100) and followed for 190 days post dose. Efficacy endpoints were Endpoint Adjudication Committee-determined relative risk reduction (RRR) of SA pneumonia incidence in suvra vs. placebo recipients within 30 days post dose (primary endpoint, tested at 2-sided α = 0.1), incidence of all-cause pneumonia, and all-cause pneumonia or death. Serum suvra PK and levels of AT NAbs were measured through 90 days post dose and analyzed for statistical correlation. Treatment-emergent adverse events (TEAEs) and serious AEs (SAEs) were assessed through 190 days post dose.

Results
Baseline characteristics were similar between groups. Suvra provided 31.9% RRR in incidence of SA pneumonia vs. placebo (17.7% vs. 26%; P = 0.166), 30% RRR (P = 0.146) in incidence of all-cause pneumonia, and 23% RRR (P = 0.164) in incidence of all-cause pneumonia or death. Suvra reduced mean hospital stay and ICU duration by 3.0 and 2.4 days, resp. vs. placebo. Mean serum ± SD suvra level was 296 ± 131 µg/mL at 30 days post dose. Serum AT Nab ± SD levels reached 156.03 ± 72.48 IU/mL at 2 days post dose, declining slowly to 33.74 ± 16.04 IU/mL by 90 days post dose. AT NAbs correlated with PK (r2 = 0.7), thereby confirming functional activity of suvra over time. Proportion of subjects with TEAEs or SAEs was similar between groups: ≥1 TEAE (93.8% suvra; 93.0% placebo); ≥1 serious; and/or ≥grade 3 severity SAE (66.7% suvra; 58.0% placebo).

Conclusion
A single intravenous dose of suvra produced a trend toward reduced incidence of SA pneumonia, health resource savings, sustained functional exposure in serum, and an acceptable safety profile. These results support continued development of suvra in MV ICU patients.

Disclosures
All Authors: No reported Disclosures.
2848. Spatial Distribution of Community-Acquired Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Infections and its Association with Sewer Overflows in Middle Georgia
Authors: Omatsone Margaret , Ponce-Terashima Rafael , Cole Baker Thomas 
Published: October 2019

Abstract

Background
Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) were described first in relation to hospital-acquired infections. However, infections by these organisms acquired in the community have become a public health problem. There are no well-known risk factors for acquisition of these bacteria in the community. Surface waters and sanitation conditions may serve as reservoir and transmission.

Methods
We conducted a retrospective study over 12 months of patients who had positive cultures with ESBL-PE in our laboratory. We excluded patients with hospitalization in the previous 3 months, those in skilled nursing facilities, and those whose culture was taken 3 or more days after hospitalization. Geographic Information System analysis was performed based on patient’s residence, population, and sewer overflow public data.

Results
Among 485 patients with cultures positive for ESBL-PE in 2018, 64 were included in the study. Mean age was 54, and 68.7% were females. Organisms isolated were E. coli (78.2%) and K. pneumoniae ESBL (21.8%). These were isolated from urine 47 (73.4%), blood 5 (7.8%), abscess 6 (9.3%), ulcers 5 (7.8%), and sputum 1 (1.5%). Antibiotic exposure in the preceding 3 months was noted in 12 patients (18.7%). Spatial distribution of patients in the community was not random based on nearest neighbor analysis (Z score = −2.6). Kernel density estimation showed clustering of cases. Infection rates were calculated per census tracts. There was poor correlation between infection rate and mean family income (R2 = 0.18, P = 0.017). Analysis of Kernel density estimations showed that sewer overflow distribution explained over 50% of the variance of distribution of cases with ESBL-PE (R2 = 0.51, P < 0.001).

Conclusion
Patients presenting with infections due to ESBL-PE acquired in the community did not have a random spatial distribution. Other factors besides prior antibiotic use and financial status should be investigated. Proximity to sanitary sewer overflows may be a contributing factor. Location of residence within a community may aid in identifying patients at risk for acquisition of ESBL-PE.

Disclosures
All Authors: No reported Disclosures.
2894. Metrics of Antimicrobial Use Within Inpatient Settings: Impacts of Statistical Methods and Case-Mix Adjustments
Authors: Goto Michihiko , Nair Rajeshwari , Alexander Bruce , Beck Brice , Richards Christopher , Perencevich Eli N , Livorsi Daniel J 
Published: October 2019

Abstract

Background
The necessary data elements and optimal statistical methods for benchmarking hospital-level antimicrobial use are still being debated. We aimed to describe the relative influence of case-mix adjustment and different statistical methods when ranking hospitals on antimicrobial use (AU) within inpatient settings.

Methods
Using administrative data from the Veterans Health Administration (VHA) system in October 2016, we calculated total antimicrobial days of therapy (DOT) and days present according to the National Healthcare Safety Network (NHSN) protocol. Patient-level demographics, comorbidities, and recent procedures were used for case-mix adjustments. We compared hospital rankings across 4 different methods: (A) crude antimicrobial DOT per 1,000 days present, aggregated at the hospital-level; (B) observed/expected (O/E) AU ratio with risk adjustment for ward-level variables (analogous to NHSN’s Standardized Antimicrobial Administration Ratio); (C) O/E AU ratio with risk adjustment for ward-/patient-level variables; (D) predicted/expected (P/E) AU ratio with risk adjustment for ward-/patient-level variables, based on a multilevel model accounting for clustering effects at hospital- and ward-levels.

Results
The cohort included 165,949 DOTs and 318,321 days present at 122 acute care hospitals within VHA. Crude DOTs per 1,000 days present ranged from 153.6 to 900.8 (Figure A), and ward-level risk adjustment only modestly changed rankings (Figure B). When adjusted for ward- and patient-level variables (including demographics, 14 comorbidities and 22 procedures), rankings changed substantially (Figure C). Risk-adjustment by a multilevel model changed rankings even further, while shrinking variabilities (Figure D). Ten hospitals in the lowest and 11 hospitals in the highest quartiles by O/E risk adjustment for only ward-level variables were classified to different quartiles on P/E risk adjustment.

Conclusion
We observed that the selection of variables and statistical methods for case-mix adjustment had a substantial impact on hospital rankings for antimicrobial use within inpatient settings. Careful consideration of methodologies is warranted when providing benchmarking metrics for hospitals.

Disclosures
All Authors: No reported Disclosures.
2896. Reduction in Liver-related Mortality Among HCV Infected Persons Is Driven by Attainment of SVR Independent of the Regimen Used: Results from the ERCHIVES Cohort
Authors: Butt Adeel A , Yan Peng , Aslam Samia , Lo Re III Vincent , Shaikh Obaid 
Published: October 2019

Abstract

Background
Beneficial effect of hepatitis C virus (HCV) treatment with directly acting antiviral agents (DAAs) upon overall mortality is well-established. However, the effect of treatment upon liver-related mortality is not well documented.

Methods
We used ERCHIVES database to identify all chronic HCV-infected persons between January 1, 2002 and December 31, 2016. We excluded those with HIV or HBV coinfection or hepatocellular carcinoma. HCV treatment status was defined as prescription of pegylated interferon (PEG)/ribavirin (RBV) for >24 weeks, PEG/RBV plus boceprevir or telaprevir, or a newer DAA regimen for >8 weeks. Propensity score-matched untreated controls were identified for each treated person. We linked HCV+ cases to the National Death Index (NDI) data updated to the end of 2016. Cause of death was retrieved from the underlying cause listed on the death certificate by using ICD‐10 codes. The listed primary cause was assigned as the cause of death. Each cause of death was categorized as “Liver related” or “Not liver related” by two physician members of the study team. Liver-related causes included viral hepatitis-related causes, complications of liver disease, and hepatocellular carcinoma, but excluded any cause where alcohol or any other known liver disease other than viral hepatitis was specified. Discordant results were adjudicated by a third physician member.

Results
Among 34,412 treated and 21,287 untreated controls, there were 13,098 deaths, of which 2,474 (18.9%) were liver related. Overall liver-related mortality rate per 100 person-years of follow-up was 0.64 in the treated and 1.24 in the untreated group (P). Among the treated group, the liver-related mortality rate per 100 person-years was 0.14 for those who achieved SVR and 1.26 among those who did not achieve SVR. When stratified by treatment regimen, those treated with PG/RBV had a mortality rate of 0.73 vs. 0.24 for those treated with a DAA regimen. However, further stratification by attainment of SVR revealed that the difference between regimens was almost entirely driven by the difference in SVR rates (see table).

Conclusion
HCV-infected persons who receive treatment have a substantial reduction in liver-related mortality. This reduction is largely driven by attainment of SVR and is independent of the regimen use when stratified by SVR attainment.

Disclosures
All Authors: No reported Disclosures.
2897. Collocated Buprenorphine Is Associated with Improved HCV Visit Adherence in People Who Inject Drugs (PWID): Data From the ANCHOR Study
Authors: Rosenthal Elana S , Silk Rachel , Mathur Poonam , Eyasu Rahwa , Nussdorf Laura , Hill Kristi , D’Amore Aaron , Brokus Christopher , Bijole Phyllis , Jones Miriam , Kier Randy , Sternberg David , Masur Henry , Kottilil Shyam , Kattakuzhy Sarah 
Published: October 2019

Abstract

Background
Engaging PWID in HCV treatment and monitoring for reinfection is critical to eliminate HCV and improve health in people who use drugs. However, PWID are often marginalized and can be difficult to engage and retain in care. The collocation of HCV treatment with buprenorphine to treat opioid use disorder (OUD) may improve visit adherence in this population.

Methods
ANCHOR is a single-center study evaluating treatment of HCV in PWID with chronic HCV, OUD, and IDU. Participants receive sofosbuvir/velpatasvir x12 weeks and are offered collocated buprenorphine. HCV visits occur at weeks 4, 12, 24, 48, 72 and 96.

Results
At screening, the 100 enrolled patients were predominantly male (76%), black (93%), middle-aged (median 57years), injected opioids daily or more (58%), and were not on OAT (67%). Fifty-five (55%) patients were initiated on collocated buprenorphine at some point after day 0.
Being on collocated buprenorphine at the time of HCV visit was associated with increased likelihood of visit attendance at weeks 12 (P = 0.002), 24 (P = 0.01), 48 (P = 0.02), 72 (P = 0.003), and 96 (P = 0.04). For patients who attended study visits, being on collocated buprenorphine was associated with a shorter time between planned visit and actual visit at weeks 12 (P = 0.03), 24 (P = 0.04), and 48 (P = 0.04). When looking at patients not on collocated buprenorphine, being on noncollocated opioid agonist therapy vs. not being on OUD treatment did not impact visit adherence.

Conclusion
Evidence-based treatment of HCV and OUD are critical to improving health in PWID. The collocation of HCV treatment with office-based buprenorphine may improve adherence to visits and visit timing, especially in long-term follow-up. Infectious disease providers should offer collocated buprenorphine as a tool to improve long-term outcomes and engagement in this high-risk population.

Disclosures
All Authors: No reported Disclosures.
2898. Achieving Hepatitis C SVR12 of 95% in Mono-Infected Patients with Severe Comorbidities Using Volunteer Staff and Minimal Clinic Visits and Phlebotomy
Authors: van der Horst Charles M , Greenberg Gary , Kirchgessner Erin , Vaughn Amanda , Alfano-Sobsey Edie , Riggleman Amy , Soufan Ayat , Horner Mandy , Nadabar Asha , Castillo Diana , Campbell Elizabeth , Lynn Ledford Sue 
Published: October 2019

Abstract

Background
HCV is the most common chronic bloodborne infection in the United States with an estimated 3.5 million infected. With direct-acting antivirals, cure can be achieved in 8 to 12 weeks. To achieve WHO elimination targets by 2030 (>90% reduction in incidence) requires increased detection, access to care, and simpler treatment protocols that patients, challenged by substance use and mental health disorders, can readily complete.

Methods
In 2016, Wake County, NC began HCV testing at 32 sites finding prevalence >10% at 5 shelters and drug treatment centers. An adapted simplified HCV treatment protocol, used in the high prevalence settings of Ukraine and Burma, was implemented at the Open Door Clinic – a free clinic for uninsured persons living in poverty in Wake County. After initially using genotype-specific therapy, we switched to pan-genotypic sofosbuvir/velapatisvir (SOF/VEL) for 12 weeks. Clinic visits were limited to pre-treatment and 12 weeks after treatment completion. Patients were contacted weekly via text to check on their health and adherence.

Results
Thirty HCV mono-infected patients have initiated treatment including 9 women. 21 were infected by IDU, 5 by transfusion, 3 by sex with an infected partner, and 5 have unknown risk. In genotype (GT) testing 22 have GT1, 3 GT 2, and 4 GT3. Major comorbidities include 24 with current or recent IDU, alcohol dependency, psychotic depression or schizophrenia, or missing all medical appointments other than the HCV. Twenty-seven of 30 have completed their prescribed course of HCV therapy and 20 have achieved an SVR at 12 weeks. The 1 patient who failed was admitted to the hospital 4 times in the first 6 weeks of treatment and did not take his medication consistently. An additional 2 remain on treatment and 6 are awaiting results of testing done at 12 weeks post-therapy completion. One patient died within 2 weeks of initiating therapy due to a perforated duodenal ulcer.

Conclusion
Using targeted on-site HCV testing, we identified high prevalence sites. Implementing a simplified HCV treatment program reduces patient and clinic burden and resulted in 95% achieving SVR12 despite severe comorbidities. Expansion of this program to other clinics in Wake County is underway.

Disclosures
All Authors: No reported Disclosures.
1136. Antifungal Prescribing Patterns among Hospitalized Children in the United States: Are There Opportunities for Antifungal Stewardship?
Authors: Eguiguren Lourdes , Bio Laura , Lee Brian R , Newland Jason , Hersh Adam , Gerber Jeffrey , Kronman Matthew , Lee Grace , Schwenk Hayden 
Published: October 2019

Abstract

Background
Antifungal stewardship may help reduce the toxicity, cost, and emergence of resistance related to inappropriate antifungal use. A better understanding of antifungal prescribing patterns, particularly in high-risk, high-utilization populations, is needed to guide appropriate stewardship interventions. We analyzed antifungal prescribing characteristics, including the indications for use and differences between oncology/bone marrow transplant (Onc/BMT) and non-Onc/BMT patients, using a multi-center national cohort of hospitalized children.

Methods
We analyzed antifungal prescribing data from 32 hospitals that participated in the SHARPS Antibiotic Resistance, Prescribing, and Efficacy among Children (SHARPEC) study, a point prevalence survey conducted quarterly between June 2016 and December 2017. We included inpatients <18 years of age with an active order for a systemic antifungal agent and evaluated the patient and antifungal characteristics. In the Onc/BMT group, we classified antifungal prescribing by indication and compared the proportion of antifungal prescriptions in each category based on antifungal class, route of administration, and use of combination therapy.

Results
Six percent (2,095/34,927) of patients received a total of 2,207 antifungal prescriptions. Fifty-eight percent (1,291/2,207) of antifungal prescriptions were for Onc/BMT patients. Among patients prescribed an antifungal, those with an Onc/BMT diagnosis were older, received broader-spectrum agents, and were more likely to receive combination therapy (Table 1). The majority of antifungal use in the Onc/BMT group was for prophylaxis, with significant variation in the rate and choice of prophylactic antifungal prescribing across hospitals (Figure 1). Combination antifungal use was common among Onc/BMT patients receiving targeted therapy (Table 2).

Conclusion
The majority of antifungal use among hospitalized children is for patients with an Onc/BMT diagnosis and the patterns of antifungal utilization in this population appear to differ significantly from non-Onc/BMT patients. Based on the variation observed in this nationwide cohort, potential stewardship targets include the rate and type of antifungal prophylaxis and the use of combination therapy in Onc/BMT patients.

Disclosures
All authors: No reported disclosures.
1139. Multidisciplinary Initiative to Increase Guideline-Concordant Antibiotic Prescriptions at Discharge for Hospitalized Children with Uncomplicated Community-Acquired Pneumonia
Authors: Yonts Alexandra B , Bozzella Michael Jason , Magyar Matthew , O’Neill Laura , Harik Nada 
Published: October 2019

Abstract

Background
Community-acquired pneumonia (CAP) is the most common diagnosis in hospitalized children. The Pediatric Infectious Diseases Society and the Infectious Diseases Society of America published evidenced-based clinical practice guidelines for the management of CAP in children 3 months of age or older in 2011. These guidelines are not consistently followed. Our objective was to evaluate if quality improvement (QI) methods could improve guideline-concordant antibiotic prescribing, specifically addressing the use of oral third-generation cephalosporins, at hospital discharge for children with uncomplicated CAP.

Methods
QI interventions, implemented at a single tertiary care children’s hospital in Washington, D.C., focused on key drivers targeting hospital medicine resident teams. Multiple plan-do-study-act (PDSA) cycles were performed. Initial interventions included educational sessions (in small group and lecture formats) aimed at pediatric resident physicians, as well as visual job aids (Figure 1) and guideline summaries posted in resident physician work areas. Interventions were implemented in series to allow for statistical analysis via run chart. Medical records of eligible patients were reviewed monthly after each intervention to determine the impact on appropriate discharge antibiotic prescribing.

Results
At baseline, the median percentage of children with a diagnosis of uncomplicated CAP discharged with guideline-concordant antibiotics was 50%. Median rates of guideline-concordant antibiotic prescribing improved to 87.5% after initial interventions (Figure 2).

Conclusion
A fellow-led multidisciplinary QI initiative was successful in decreasing rates of non-guideline-concordant antibiotic prescribing at discharge. These interventions can be tailored for use at other institutions and for other infectious processes with established treatment guidelines. To ensure sustained improvement in guideline-concordant prescribing, future planned interventions include additional educational sessions with residents, faculty, and pharmacists, EMR order set modification and physician benchmarking. These tactics are intended to address the anticipated challenge of resident/faculty turnover and automate antibiotic choice for uncomplicated CAP.

Disclosures
All authors: No reported disclosures.
1154. Impact of Educational Feedback on Reducing Hospital-Onset Catheter-Associated Urinary tract Infections at an Academic Medical Center
Authors: Navalkele Bhagyashri D , Truhett Nora , Ward Miranda , Fletcher Sheila 
Published: October 2019

Abstract

Background
High regulatory burden on hospital-onset (HO) infections has increased performance pressure on infection prevention programs. Despite the availability of comprehensive prevention guidelines, a major challenge has been communication with frontline staff to integrate appropriate prevention measures into practice. The objective of our study was to evaluate the impact of educational intervention on HO CAUTI rates and urinary catheter days.

Methods
At the University of Mississippi Medical Center, Infection prevention (IP) reports unit-based monthly HO infections via email to respective unit managers and ordering physician providers. Starting May 2018, IP assessed compliance to CAUTI prevention strategies per SHEA/IDSA practice recommendations (2014). HO CAUTI cases with noncompliance were labeled as “preventable” infections and educational justification was provided in the email report. No other interventions were introduced during the study period. CAUTI data were collected using ongoing surveillance per NHSN and used to calculate rates per 1,000 catheter days. One-way analysis of variance (ANOVA) was used to compare pre- and post-intervention data.

Results
Prior to intervention (July 2017–March 2018), HO CAUTI rate was 1.43 per 1,000 catheter days. In the post-intervention period (July 2018–March 2019), HO CAUTI rate decreased to 0.62 per 1,000 catheter days. Comparison of pre- and post-intervention rates showed a statistically significant reduction in HO CAUTIs (P = 0.04). The total number of catheter days reduced, but the difference was not statistically significant (8,604 vs. 7,583; P = 0.06). Of the 14 HO CAUTIs in post-intervention period, 64% (8/14) were reported preventable. The preventable causes included inappropriate urine culturing practice in asymptomatic patients (5) or as part of pan-culture without urinalysis (2), and lack of daily catheter assessment for necessity (1).

Conclusion
At our institute, regular educational feedback by IP to frontline staff resulted in a reduction of HO CAUTIs. Feedback measure improved accountability, awareness and engagement of frontline staff in practicing appropriate CAUTI prevention strategies.

Disclosures
All authors: No reported disclosures.