bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Flaccid Myelitis Cases Presenting During a Spike in Respiratory Enterovirus D68 Circulation: Case Series From a Single Pediatric Referral Center.
Authors: Naccache Samia , Bender Jeffery , Desai Jay , Van Tam , Meyers Lindsay , Jones Jay , Mongkolrattanothai Kanokporn , Bard Jennifer Dien
Published: October 2017

Background

In 2014, a global outbreak of Enterovirus D68 (EV-D68) caused severe respiratory disease and was associated with an increase in acute flaccid myelitis (AFM) cases. Despite heightened surveillance, both EV-D68 detection and AFM reporting dropped in 2015. As AFM reporting increased in 2016, we sought to better understand AFM and EV-D68 epidemiology at our institution.

Methods

Chart review of clinical presentation and workup was conducted on patients meeting the case definition for AFM for 2015-16. To determine EV-D68 prevalence at CHLA, samples positive for Rhinovirus/Enterovirus (RV/EV) by FilmArray® Respiratory Panel (FA-RP) in September 2016 were screened for EV-D68 by RT-PCR. Results were compared with a research algorithm developed within the FilmArray®Trend epidemiology software. After establishing accurate EV-D68 prediction, the algorithm was used on historic FA-RP assays to measure EV-D68 prevalence at CHLA in 2015 and 2016.

Results

7 patients with a median age of 3.3 years and no significant past medical history presented with AFM between July 15 - October 15, 2016, while none were identified in 2015. All had acute onset patchy weakness involving mostly the upper limbs and grey matter involvement on MRI. 6/7 reported fever/upper respiratory infection prior to AFM onset. CSF from 7/7 was negative by FilmArray®meningitis/encephalitis Panel and 2/7 were positive for EBV DNA. Further work up on CSF and blood were negative. 4/7 (57.1%) patients were RV/EV positive from respiratory samples and 3 were confirmed as EV-D68 by RT-PCR. IVIG was given in 7/7 cases. Patients were discharged after an average of 8.8 (4.8-13.6) days. The FilmArray Trend monitoring revealed that during the time of AFM presentation in 2016, 226/778 patients tested for respiratory viruses by the FA-RP were positive for RV/EV. Of those, 29.2% (66/226) were positive for EV-D68 compared with 0.02% (2/224) over the same period in 2015.

Conclusion

As shown by CDC surveillance data, we saw a resurgence of AFM cases in 2016 compared with 2015. All 7 patients identified were previously healthy and had persistent weakness at discharge. Cases were accompanied by increases in circulating respiratory EV-D68. Further investigation of the correlation between EV-D68 resurgence and AFM is warranted.

Disclosures

L. Meyers, BioFire Diagnostics: Employee, Salary. J. Jones, Biofire Diagnostics LLC: Employee, Salary. J. Dien Bard, BioFire: Consultant and Investigator, Research grant and Speaker honorarium.
Lyme Disease in Hispanics in Long Island, New York: A New Health Disparity in the U.S.
Authors: Khoo Teresa , Spallone Amy , Lier Audun , Abul Yasin , Wellins Anna-Marie , Weinbaum Fredric , Luft Benjamin , Marcos Luis A
Published: October 2017

Background

Lyme disease (LD) is the most commonly reported vector-borne illness in the U.S. A risk factor for acquiring LD is the exposure to outdoors. In Long Island, Hispanics compromise a large share of the outdoor occupational workforce.

Methods

A retrospective chart review was performed in all patients with ICD-9 or ICD-10 diagnostic codes for LD between 2011–2016 in SHH and 2010–2015 in SBUH. Inclusion criteria was defined as a clinical scenario compatible with LD (erythema migrans -EM, arthritis, central nervous system (CNS) involvement, carditis, meningitis) and serological confirmation by western blot according to CDC (SBUH) or Imugen® (SHH) criteria.

Results

Out of 1,026 cases (766 SBUH;260 SHH) that carried a diagnosis of LD, 284 cases (22% Hispanics) met inclusion criteria and were added to final analysis (241 SBUH: 43 SHH). The mean age was 48.8 (SD:17.8) and 48.3 (SD:17.5) years-old in H and NH, respectively (p > 0.05). Most were male (H:62.2%; NH: 54.3%; P = 0.2). In the univariate analysis, headaches were more frequently present in H (42.6%) than in NH (26.6%) (P = 0.015). In the logistic regression analysis, the following symptoms were significantly different between H and NH: headaches (OR 1.17, 96% CI 1.60–6.59,  P = 0.001) and peripheral neuropathy (OR 0.38, 95% CI: 0.15-0.96, P = 0.04). Among seasons, H were more frequently diagnosed with Lyme during spring months than NH (H: 26.3% vs. NH: 12.6%, P = 0.03)

Conclusion

Hispanics have a greater risk for presenting with headaches and less peripheral neuropathy than NH. Initiation of outdoor work among H may be the reason of this disproportionate presentation of LD symptoms during spring months. These findings may suggest the propensity for Hispanics to go underdiagnosed with LD, despite their high likelihood of exposure through their occupations in this region.

Disclosures

All authors: No reported disclosures.
Serum and Lung Pharmacokinetics of ASN100, a Monoclonal Antibody Combination for the Prevention and Treatment of Staphylococcus aureus Pneumonia
Authors: Magyarics Zoltan , Leslie Fraser , Luperchio Steven A , Bartko Johann , Schörgenhofer Christian , Schwameis Michael , Derhaschnig Ulla , Lagler Heimo , Stiebellehner Leopold , Jilma Bernd , Stevens Christopher , Nagy Eszter
Published: October 2017

Background

Monoclonal antibodies (mAbs) are well-suited for the prevention and treatment of acute bacterial infections. ASN100 is a combination of two fully human IgG1 mAbs, ASN-1 and ASN-2 that together neutralize six Staphylococcus aureus cytotoxins, alpha-hemolysin (Hla) and five leukocidins (HlgAB, HlgCB, LukED, LukSF [PVL] and LukGH) that are important in the pathogenesis of S. Aureus pneumonia. We aimed to characterize the pharmacokinetics (PK) of ASN100 in both serum and lung epithelial lining fluid (ELF) in male and female healthy volunteers.

Methods

The safety, tolerability, and serum and lung PK of single intravenous infusion of ASN100 was evaluated in a Phase 1 study. Eight subjects (3:1 randomization) in two double-blind cohorts received ASN100 (doses of 3600 mg or 8000 mg) or placebo. ASN-1 and ASN-2 were administered in a fixed dose 1:1 ratio. Twelve subjects received ASN100 open-label at doses of 3600 mg or 8000 mg and each underwent two bronchoalveolar lavage (BAL) fluid collections either on days 1 and 30 or on days 2 and 8 post-dosing. ASN-1 and ASN-2 concentrations were determined by ELISA. The ELF concentrations were normalized based on urea concentrations in serum and BAL fluid.

Results

No dose limiting toxicity was observed. Adverse events (AEs) showed no association of increased incidence with higher dose. All AEs were mild or moderate in severity, with 83.3% of subjects receiving ASN100 reporting at least one AE vs. 100% of placebo subjects. A dose proportional increase in serum peak and exposure (AUC) of ASN-1 and ASN-2 was observed and the serum PK of ASN-1 and ASN-2 were comparable (approximate half-life of each antibody was 3 weeks). Penetration of ASN-1 and ASN-2 into the ELF of the lung was observed at the first post-dose time point of 24 hours, peak concentrations were observed after day 2 and the mAbs remained detectable at day 30.

Conclusion

ASN100 was safe and well tolerated at doses up to 8000 mg (4000 mg ASN-1 and 4000 mg ASN-2). The PK profiles of ASN-1 and ASN-2 were comparable following simultaneous administration. Significant lung concentrations of each mAb were demonstrated between day 1 and 30 post-dosing. These data support continued clinical development of ASN100 for the prevention and treatment of S. Aureus pneumonia.

Disclosures

Z. Magyarics, Arsanis Biosciences GmbH: Employee, Salary. Arsanis, Inc.: Shareholder, Share options. F. Leslie, Arsanis., Inc.: Employee and Shareholder, Salary. S. A. Luperchio, Arsanis Inc.: Employee and Shareholder, Salary. B. Jilma, Arsanis Biosciences GmbH: Investigator, Investigator fee. C. Stevens, Arsanis Inc.: Employee and Shareholder, Salary.E. Nagy, Arsanis: Employee and Shareholder, Salary.
Comparison of Viral Loads in Patients with Co-infections vs. Single-virus Infections
Authors: Beveridge Stockton , Piya Bhinnata , Stewart Laura , Lindegren Mary Louise , Markus Tiffanie , Schaffner William , Halasa Natasha B
Published: October 2017

Background

Molecular testing for respiratory viruses in clinical practice is common, often with multiple viruses detected. Viral load has been correlated with illness severity, but correlation of co-detection of viruses and viral load is less clear. We sought to compare cycle threshold (Ct) values, a marker inversely related to viral load, between single vs. co-detection of common respiratory viruses.

Methods

Children <18 years with respiratory symptoms and/or fever who presented to the ED or were admitted were enrolled. Nasal/throat specimens were obtained and combined. Singleplex qRT-PCR was used to test for 11 respiratory viruses. Clinical and demographic information were collected.

Results

From 11/15/15-7/15/16, 1255 children were enrolled, with median age of 26.5 months, 53.4% male, 54.3% White, 38.7% Black, 6.4% other, and 23.5% Hispanic. The median days of illness were 3 days. Of the total cohort, 904 (72%) tested positive for at least one viral pathogen. Table 1compares Ct values of single vs. co-detection for each individual virus.

Conclusion

Single detection with RSV, HRV, AdV, and PIV had lower Ct values, indicating higher viral loads, compared with co-detection with other viruses. Additional research is needed to understand the reason for lower viral loads for co-detection vs. single detection in select respiratory viruses.

Disclosures

W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. N. B. Halasa, sanofi pasteur: Research Contractor, Research support. Astra Zeneca: Research Contractor, Grant recipient.
Pharmacokinetics (PK) and Safety of Intravenous (IV) Brincidofovir (BCV) in Healthy Adult Subjects
Authors: Wire Mary Beth , Morrison Marion , Anderson Maggie , Arumugham Thangam , Dunn John , Naderer Odin
Published: October 2017

Background

BCV is a lipid conjugate nucleotide that has shown rapid viral clearance in patients with adenovirus infection and improved survival in animal models of smallpox. In preclinical studies in rats, IV BCV dosed twice weekly for up to 29 days was not associated with gastrointestinal (GI), hematopoietic, hepatic, or renal toxicity. This study evaluated the safety and PK of IV BCV in healthy subjects.

Methods

In this double-blind study, subjects were randomized 3:1 to receive IV BCV or placebo in sequential single ascending dose cohorts (Table 1). Plasma PK samples were collected over 7 days and assayed by HPLC-MS. Plasma BCV PK parameters were determined by non-compartmental analysis and dose proportionality was assessed. Safety assessments were collected over 14 days.

Results

Forty healthy male subjects (18–46 years, 83% White) were enrolled and completed the study. Plasma BCV Cmax and AUC∞ increased in proportion to dose (Table 1). AEs and alanine aminotransferase (ALT) elevations were dose- and infusion duration-related (Table 1). GI AEs were mild. All AEs and ALT elevations were transient and no serious AEs occurred.

Conclusion

Single doses of BCV 10–50 mg administered as a 2h IV infusion were well tolerated and not associated with significant clinical or laboratory abnormalities. BCV IV 10 mg and BCV IV 50 mg achieved geometric mean plasma BCV AUC∞ similar to and 4.5-fold, respectively, values achieved with BCV oral 100 mg tablets (Cmax = 251 ng/mL and AUC∞ = 1394 ng hours/mL). These data support evaluation of repeat dose administration in healthy subjects and virally-infected patients.

Disclosures

M. B. Wire, Chimerix: Employee and Shareholder, Salary. M. Morrison, Chimerix: Employee and Shareholder, Salary.M. Anderson, Chimerix: Employee and Shareholder, Salary. T. Arumugham, Chimerix: Employee and Shareholder, Salary. J. Dunn, Chimerix: Employee and Shareholder, Salary. O. Naderer, Chimerix: Employee and Shareholder, Salary.
Human Coronavirus Circulation in the USA, 2014‒2017
Authors: Biggs Holly M , Killerby Marie E , Haynes Amber K , Dahl Rebecca M , Gerber Susan I , Watson John T
Published: October 2017

Background

Human coronaviruses (HCoV) OC43, 229E, NL63 and HKU1 commonly cause upper respiratory tract infections, but can also cause severe lower respiratory tract disease. Increased use of diagnostic assays for respiratory viruses has facilitated detection and, since 2014, voluntary reporting of HCoV to the National Respiratory and Enteric Virus Surveillance System (NREVSS).

Methods

We reviewed weekly aggregate test results for HCoV OC43, 229E, NL63 and HKU1 voluntarily reported to NREVSS by U.S. hospital and clinical laboratories from July 1, 2014‒April 30, 2017. Laboratories reporting any HCoV result using PCR were included, and the weekly percentage of positive HCoV tests by type was calculated. For a subset of HCoV detections reported to NREVSS via the Public Health laboratory Interoperability Project (PHLIP), which collects individual-level demographic data, we described age distribution and sex. Age distribution by HCoV type was compared using the Kruskal–Wallis test.

Results

154 laboratories, across all 9 U.S. census divisions, reported 834,742 tests for HCoV; 18,514 (2.2%) were positive for HCoV-OC43, 8,363 (1.0%) for HCoV-NL63, 6,828 (0.8%) for HCoV-229E, and 5,170 (0.6%) for HCoV-HKU1. The percentage of tests positive for HCoV generally peaked between December and March (Figure 1). HCoV-OC43 showed distinct annual peaks with variation in magnitude by year. HCoV-HKU1 and NL63 had similar patterns, each with notable peaks during winter 2016 compared with 2015 or 2017. HCoV-229E showed a discernable peak in 2017 compared with the previous 2 years. Of 20,533 individuals with HCoV test results reported via PHLIP, 1,589 (7.7%) tested positive for any HCoV; 50% of HCoV-positive individuals were male, and the median age was 22 (range 0–96) years. Age distribution differed between HCoV types (P < 0.01, Figure 2).

Conclusion

Over approximately 3 seasons, peak positivity for HCoV occurred during winter months, and annual differences in circulation by HCoV type were observed. Continued testing and surveillance for HCoV will allow for further characterization of circulation trends over time and by geographic region, and improved understanding of the contribution of HCoV to the winter respiratory virus season.

Disclosures

All authors: No reported disclosures.
Evaluation of Serum TNF-alpha, IL-6, IL-10, and IFN-gamma Levels in Patients with Crimean–Congo Hemorrhagic Fever
Authors: Hülya Yilmaz , Yilmaz Gürdal , Kostakoglu Ugur , Arslan Mustafa , Karahan Süleyman Caner , Koksal Iftihar
Published: October 2017

Background

Crimean–Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. Cytokines plays an important role in the pathogenesis of viral, bacterial, and immunologic diseases. This study aimed to investigate the role of TNF-alpha, IL-6, IL-10, and IFN-gamma levels in the severity of infection and clinical outcome of patients with CCHF.

Methods

Patients with confirmed CCHF were divided into two groups (severe cases: Patients who exhibited hemorrhage during their hospital stay, and mild/moderate cases: Patients who displayed no hemorrhage during their hospital stay). Demographic characteristics, laboratory tests on admission of all patients with CCHF were investigated, and serum TNF-alpha, IL-6, IL-10, and IFN-gamma levels were measured.

Results

A total of 154 patients with confirmed CCHF were investigated. Forty-six (29.9%) of these patients were in the severe group. In patients with severe CCHF, significantly higher serum levels of TNF-alpha (68.2 ± 23.5; P = 0.008) and IL-6 (73.1 ± 41.6; P = 0.003) were detected, compared with cytokine levels in patients who mild/moderate CCHF (Table 1). No differences in serum IL-10 and IFN-gamma levels between patients who severe CCHF and those who mild/moderate CCHF were detected (P > 0.05).

Conclusion

Cytokines, chemokines, and other inflammatory mediators function in a manner, acting on many different cell types to regulate the host’s immune response. When cytokines present in high concentrations, they might toxic or even lethal effects. In accordance with this view, we have detected increased serum TNF-alpha, IL-6 levels in the patients with severe CCHF.

Disclosures

All authors: No reported disclosures.
Frequency of Epstein–Barr Virus Genotypes in Pakistani Trangender SexWorkers
Authors: Salahud Din Sadia
Published: October 2017

Background

Transgender community large association with sex work has put them at a greater risk of contracting sexually transmitted infections (STIs).The aim of this study was to investigate the prevalence of Epstein–Barr Virus (EBV) genotypes in transgender sex workers (TSWs) of twin-cities of Pakistan. The high prevalence of EBV-2 genotype in sex workers has been previously reported. EBV genotypes were investigated in transgender sex workers to find out EBV-2 occurrence in Pakistani population.

Methods

A total of 86 transgender (Hijras) sex workers were randomly included in this study. Demographics, including age, the number of sex partners, sexual habits, and awareness about protective methods were obtained. Blood was collected from all subjects and The presence of Human Immunodeficiency Virus, Hepatitis B and C virus were determined by antibody strip testing. EBV detection and genotyping were performed by extracting genomic DNA from all whole blood samples. Β-globin and EBNA-1 were amplified to assess the quality and presence of EBV DNA. Analysis of EBNA-2 genotyping was done by nested PCR.

Results

HIV was the most prevalent infection in 40 transgender sex workers (46.51%) followed by HCV in 15 (17.44%). Among HIV-seropositive TSW’s, EBV genotype determination was only achievable in 60% of cases, where 62.5% were EBV-1, 29.16% of EBV-2 and co-infection was found in 8% samples. Among HIV-negative individuals, 78% were EBV-1, whereas EBV-2 genotype and co-infections were absent. All non-typable samples were amplifiable for the EBNA-1 gene in both populations, confirming EBV genome in the samples.

Conclusion

EBV-1 was the most common genotype of EBV in HIV seropositive and seronegative TSW’s but the high occurrence of EBV-2 and co-infection of both types was observed only in HIV seropositive individuals. This is the first report of frequency of EBV infections in the HIV-positive transgender community of Pakistan.

Disclosures

All authors: No reported disclosures.
Estimated Hospitalization Rates for Seasonal Influenza in Adults and Children in Middle Tennessee using a Capture-Recapture Method
Authors: Ivey Kelsey S , Zhu Yuwei , Halasa Natasha B , Schaffner William , Campbell Angela P , Garg Shikha , Ferdinands Jill M , Talbot H Keipp
Published: October 2017

Background

Ongoing surveillance of influenza activity is important to monitor variation in disease severity and vaccine effectiveness, but surveillance systems have limitations. The capture-recapture method aims to more comprehensively estimate disease burden by combining data from independent studies.

Methods

Residents of 8 counties in Middle TN hospitalized with influenza during the 2015-16 influenza A(H1N1pdm09)-predominant season were identified using data from 3 independent CDC-sponsored programs. The Influenza Hospitalization Surveillance Network/Emerging Infections Program (FluSurv-Net/EIP) identifies adult and pediatric cases based on a positive clinician-ordered influenza test. The U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and the New Vaccine Surveillance Network (NVSN) enroll adults (3 hospitals) and children (1 hospital), respectively, with respiratory symptoms with/without fever, and obtain nasal/throat swabs to identify cases of influenza; 2015–2016 was a pilot year for HAIVEN. Using the numbers of matched and unmatched cases detected by two studies, a capture-recapture analysis estimated the total number (N) of influenza-related hospitalizations in the population (Table 1). Due to small sample size, the Chapman equation was used, where N = ((a + b + 1)(a + c + 1)/(a + 1)) – 1. The capture–recapture estimates were adjusted for the hospitals’ market share for acute respiratory illness in middle TN residents (69.2% for children and 23.9% for adults) based on hospital discharge data.

Results

Capture-recapture analyses based on unadjusted crude data are shown in Figure 1A and 1B. Age-specific rates of hospitalization were then calculated (Figure 1C).

Conclusion

Using a capture–recapture method, we estimated influenza hospitalization rates of 0.87 (95% CI 0.06–1.68) and 0.80 (95% CI 0.62–0.98) per 1,000 persons among children and adults, respectively.

Disclosures

N. B. Halasa, sanofi pasteur: Research Contractor, Research support. Astra Zeneca: Research Contractor, Grant recipient. W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. H. K. Talbot, Gilead: Investigator, Research support. MedImmune: Investigator, Research support. sanofi pasteur: Investigator, Research support. VaxInnate: Scientific Advisor, Consulting fee. Sequirus: Scientific Advisor, Consulting fee.
Clinical Characteristics of Parainfluenza Virus Infection among Healthy Subjects with Influenza-like Illness
Authors: Fairchok Mary , Chen Wei-Ju , Mor Deepika , Schofield Christina , Arnold John , Danaher Patrick , Deiss Robert , Lalani Tahaniyat , Rajnik Michael , Malone Leslie , Grigorenko Elena , Stalons Donald , Burgess Timothy , Millar Eugene , Coles Christian
Published: October 2017

Background

Parainfluenza virus (PIV) is a chief cause of croup. Less is known about the role of PIV in causing influenza-like illness (ILI) among healthy adults and children. We evaluated clinical characteristics of PIV compared with influenza (flu) infection in healthy subjects diagnosed with ILI.

Methods

The Acute Respiratory Infection Consortium (ARIC) conducted an observational, longitudinal study of ILI at five US military treatment facilities from 2009 to 2016. Participants were otherwise healthy military members, retirees, and their dependents. Symptom data were captured prospectively on days 0, 3, and 7 by interview and patient diary. Nasopharyngeal specimens were collected for etiologic determination by multiplex assay (Diatherix Laboratories, LLC.) Severity scores were calculated for upper respiratory, lower respiratory, GI, composite and systemic symptoms

Results

PIV did not account for a large proportion of ILI in our population with 43/961(4.7%) PIV+ vs. 153/961(15.9%) that were flu+. Age < 5 years was associated with increased detection of PIV (10% in <5 years vs. 3.2% in 5–65 years, P < 0.01). Additionally, on multivariable analysis, the presence of a child aged <5 years in the household was associated with an increased risk of PIV detection (OR = 2.58; 95% CI:1.39, 4.80). Sex, geographic location, year of detection, race/ethnicity, smoking status and obesity were all unrelated to PIV detection. Codetections occurred in 8/43 (18.6%) subjects, but codetected viruses did not show any specific pattern, with 5 different viruses found. When comparing demographic characteristics of ILI caused by flu vs. PIV, the only difference was that flu+ subjects were more often ≥5 years (P < 0.01). Comparing symptom profile and severity of adults with PIV + ILI vs. flu+, we found no differences in the presence or severity of 20 symptoms, nor in severity scores for each of the 5 categories. Rates of hospitalization, antibiotic use, or duration of illness were also indistinguishable.

Conclusion

This is one of a few studies to detail the clinical characteristics of PIV presenting as ILI in healthy subjects. PIV is more often detected in young children with ILI. Although PIV was detected 25% as often as flu, it had an indistinguishable clinical course from influenza associated ILI in adults.

Disclosures

L. Malone, diatherix: Employee, Salary. E. Grigorenko, Diatherix Laboratories: Employee, Salary. D. Stalons, Diatherix Laboratories: Employee, Salary.
Clinical and Economic Burden of Respiratory Viral Infections in Hematopoietic Stem Cell Transplant Recipients: The MD Anderson Experience
Authors: Ghantoji Shashank S , Karanth Siddharth , El Haddad Lynn , Park Anne , Lairson David , Chemaly Roy F
Published: October 2017

Background

Respiratory syncytial virus (RSV), parainfluenza virus (PIV) and influenza virus (Flu) are common respiratory viral infections (RVIs) implicated in hematopoietic stem cell transplant (HSCT) recipients. Despite their possible association with high rates of pneumonia and mortality, their clinical and economic burden has not been well studied.

Methods

HSCT recipients with documented RVI who were treated at our institution between September 2012 and October 2015 were included in the study. We used Vizient (formerly University Health Consortium) clinical database to collect and compare total costs, including length of stay, ICU admission rates, intravenous immunoglobulin use, steroid use, and mortality rates among RVIs in HSCT recipients. Encounter-specific demographics, risk factors, underlying cancer, and outcomes were also collected. Multiple linear regression analyses were applied to identify predictors of higher total cost associated with RVI in HSCT recipients at MD Anderson.

Results

Average total cost per encounter was $49,371 for RSV, $29,679 for PIV, and $15,077 for Flu. A total of 1,636 hospitalization days (d) were attributed to these RVIs with an average of 7 d per RSV, 8 d per PIV, and 5 d for Flu infection. The average ICU admission rate was 12% for RSV, 9% for PIV, and 4% for Flu. Around 11% of total RVI encounters had active graft-vs.-host disease at the time of their RVI. Out of the patients with upper respiratory infection, 20% RSV, 44% PIV, and 21% Flu progressed to pneumonia during the 28 d of the study period. Of the 246 total RVI encounters, overall all-cause mortality rate was 6% (RSV: 8% [8/98], PIV: 1% [1/70] and Flu: 8% [6/78]). Length of stay, ICU admission, and receiving intravenous immunoglobulin were strong predictors of higher cost for all RVIs.

Conclusion

This study underscores the significant impact of RVIs in terms of economic and clinical burden in HSCT recipients. Major differences in total costs per encounter across the three RVIs were observed. This cost and clinical data may be helpful for future cost effectiveness studies in this population.

Disclosures

All authors: No reported disclosures.
Vaccinating High-Risk Pediatric Patients and Their Families in the Hospital Setting: Give It a Shot!
Authors: Barros Rebecca , Gornick Wendi , Tran M Tuan , Huff Beth , Singh Jasjit
Published: October 2017

Background

Hospitalization and hospital-based clinics confer an opportunity to target high-risk patients and their families who would benefit from vaccination.

Methods

CHOC Children’s Hospital is a tertiary-care hospital in Southern California with 11,995 admissions in 2016, including 1,580 hematology/oncology (HO) admissions. We examined the trend in influenza vaccine administration in hospitalized and HO patients over the last decade. We assessed the trend in Tdap and influenza vaccine administration among parents of hospitalized children. We correlated those trends with disease outbreaks in the community and educational and programmatic efforts at our institution.

Results

After educational efforts, the influenza vaccination rate in 2017 compared with 2006 increased 13-fold in hospitalized patients and increased 9-fold among hospitalized HO patients. During the H1N1 pandemic in 2009, influenza vaccination rates increased 470% from the year prior (Figure 1). The number of influenza vaccines administered in the clinic to HO patients was 494 and 408 in 2015–2016 and 2016–2017, respectively. Following program initiation, the number of Tdap vaccines administered to parents during their child’s hospitalization increased from 57 doses in 2013 to 118 doses in 2016. The trend in vaccination roughly followed pertussis outbreak cases (Figure 2). The number of influenza vaccines administered to parents of HO patients during their child’s clinic visit increased from 44 doses given in 2015–2016 to 306 doses given in 2016–2017 (Figure 3). At our institution, among staff we achieved a 98% vaccination rate for Tdap and influenza in 2017. There were no serious adverse events reported after patient, parent or staff vaccination during this time period.

Conclusion

Missed opportunities for vaccination of high-risk children include hospitalization and specialty clinic visits. Creating a culture of vaccination and public perception of vaccine importance during outbreaks can increase the influenza vaccination rate among high-risk, hospitalized and HO patients. Programs targeting families of high-risk patients are an opportunity to cocoon a vulnerable population. Vaccination of hospitalized children, their parents and staff is safe in these settings.

Disclosures

All authors: No reported disclosures.
Indications for Antibiotic Orders: How Accurate Are They?
Authors: Heil Emily , Pineles Lisa , Morgan Daniel , Harris Anthony D , Thom Kerri
Published: October 2017

Background

Documentation of antibiotic indications at the time of ordering can provide helpful information for antimicrobial stewardship programs to track antibiotic utilization patterns and improve antibiotic prescribing. Yet accuracy of indications is not fully understood; antibiotics are often ordered empirically without a clear-cut indication, and orders are not often updated once a diagnosis has been made, or the first listed option may be chosen for convenience. As hospitals are implementing antibiotic indications at the time of order entry to meet stewardship standards, our study sought to assess the accuracy of indications in an antibiotic order compared with true indication for the drug.

Methods

Indications for antibiotics, selected from a standardized list, are a required field in the computerized order entry system at our institution. Study investigators, including at least one infectious diseases attending, performed an in-depth post-hoc review to assess antibiotic indication and appropriateness. The frequency that the true antibiotic indication, as assessed by study investigators, matched with the indication in the antibiotic order was analyzed.

Results

Of 396 antibiotic orders reviewed by the study team, 100 had discordant indications between what was written in the order and the investigator-assessed indication (25.3%). The highest rates of discordance were seen with GU-UTI (11/18 incorrect, 61.1%) followed by bacteremia/sepsis (44 of the 116 incorrect, 37.9%). For GU-UTI, the most common investigator assessed true indications were pulmonary including CAP, HAP and empyema. For bacteremia/sepsis, the discordance was often due to a more specific diagnosis or source being identified.

Conclusion

Discordant indications between what was entered at the time of initial order compared with an investigator assessed indication occurred frequently. This finding is of concern as evaluations of antibiotic appropriateness, utilization and benchmarking by the antimicrobial stewardship team rely on the accuracy of indications in the system. Entering a revised indication during an antibiotic time out could improve the accuracy of antibiotic indications and antimicrobial stewardship data.

Disclosures

All authors: No reported disclosures.
Population-Level Hepatitis C Testing Using A Personal Electronic Health Portal System Significantly Improves Screening Rates in Baby Boomers
Authors: Hojat Leila , Kaelber David , Avery Ann
Published: October 2017

Background

Hepatitis C virus (HCV) infection is a major public health burden. The USPSTF and CDC have both released guidelines which recommend screening the baby boomer population (individuals born between 1945 and 1965) given the overrepresentation of HCV infection in this cohort. However, screening rates remain low despite prior attempts at improvement.

Objective

To improve HCV testing rate in the birth cohort in compliance with national guidelines without increasing primary care provider workload or alert fatigue.

Methods

We developed a population health initiative that employed EHR-based tools involving direct patient messaging and bulk lab test ordering via a personal electronic health portal system. This was completed independent of a face-to-face interaction between the patient and provider.

Results

We collected data on 1,024 patients total (514 in the intervention group and 510 in the control group) over a 12-week period. We found a statistically significant higher test completion rate within the intervention group vs. the control group after this initiative was launched: 33.7% in the intervention group (173/514) vs. 19.0% in the control group (97/510) (p-value <0.0002, OR 2.16, 95% CI 1.62–2.88). Bulk lab ordering appeared to have a large impact while bulk messaging appeared to have a less significant role.

Conclusion

To our knowledge, this is the first EHR-based population health initiative to involve obtaining blood work without a direct face-to-face encounter between the provider and patient. This methodology has a broad range of applications including any recommended screening or disease-specific testing, and it will be essential for health systems to adopt similar protocols as we progress toward a pay-for-performance reimbursement model.

Disclosures

All authors: No reported disclosures.
Utilizing a Post-discharge Telephone Call in Outpatient Parenteral Antimicrobial Therapy (OPAT): Findings from a Quality Improvement Project
Authors: Felder Kimberly , Vaz Louise , Barnes Penelope , Varley Cara
Published: October 2017

Background

Transitions of care from hospitals to outpatient settings, especially for patients requiring outpatient parenteral antimicrobial therapy (OPAT) are complex. OPAT complications, such as adverse antimicrobial reactions, vascular access problems, and hospital readmissions are common. Data from transitions of care literature suggest that post-discharge telephone calls (TCs) may significantly decrease re-hospitalization but no studies have assessed the utility of post-discharge TCs as an OPAT program quality improvement process.

Methods

Adult OPAT patients discharged from our hospital between April 1, 2015 and May 31, 2016 were queried for post-discharge concerns. TCs to patients or their caregivers were administered by trained medical assistants within the Department of Infectious Diseases using a standardized script and documented in the electronic medical record (EMR). Feasibility was assessed using call completion rate. The type and frequency of reported issues were analyzed by retrospective chart review.

Results

636 of 689 eligible adult OPAT patients or their caregivers received a TC with responses to scripted questions documented in the EMR (92% completion rate). 302 patients (47%) reported 319 issues, including 293 (92%) relevant to OPAT. Antimicrobial issues included diarrhea/stool changes (58; 9%); nausea/vomiting (27; 4%); and missed antimicrobial doses (22; 3%). Vascular access issues included line patency concerns (21; 3%); vascular access dressing problems (17; 2.6%) and arm pain/swelling (6; 1%). OPAT vendor issues included delays in lab or line care services (23; 4%) and OPAT orders reported as lost/not received (21; 3%). Other ID-related issues included fevers/chills/sweats (27; 4%), wound concerns (16; 2.5%), and pain (15; 2.5%).

Conclusion

Adding a post-discharge TC to an OPAT program was feasible and resulted in frequent and early identification of significant OPAT patient and caregiver concerns. Findings suggest potential high-yield topics for process improvement, as well as anticipatory guidance and patient education in OPAT. Further evaluation and analysis of optimal hospital discharge processes and care coordination in OPAT, as well as their impact on post-discharge adverse events, is needed.

Disclosures

All authors: No reported disclosures.
Impact of an Antimicrobial Stewardship Program Led OPAT Program on Clinical Complications and Frequency of Hospital Readmissions
Authors: Carr J Andrew , Baddley John W , Heath Sonya , Lee Rachael A , McCarty Todd P
Published: October 2017

Background

Treatment of serious bacterial infections with Outpatient Parenteral Antibiotic Therapy (OPAT) has provided patients (patients) the opportunity to complete treatment safely and effectively, while avoiding complications, and prolonged hospitalization. Despite the benefits, considerable risks with drug-related and central venous catheter (CVC)-related complications exist. We sought to improve clinical outcomes of our program by implementing intensive monitoring in partnership with our antimicrobial stewardship program (ASP) with a goal of decreasing the frequency of complications as well as hospital readmission rates and lengths of stay (LOS).

Methods

A retrospective study was conducted including all patients discharged from the Birmingham VA Medical Center on OPAT from January 1, 2015 to December 31, 2016. The start date coincides with ASP development of a physician and pharmacist led OPAT program, working closely with home health agencies. Data collection included baseline demographics, antibiotic indication, antibiotic therapy received, and laboratory monitoring. Clinical outcomes included frequency and types of drug-related complications, CVC complications, hospital admission rate due to complications, and hospital days avoided.

Results

In the study period, 299 patients were discharged on OPAT. They were 96.9% male, and the average age was 64 (Table 1). The average number of hospital days avoided was 32.1. The most common indication was osteomyelitis (Table 1). There were 82 complications in 78 (26%) patients, almost half were acute kidney injury, defined as a rise in serum creatinine requiring a change in antibiotic dosing (Table 2). These led to 25 hospitalizations (32% of patients with complications, 8.3% overall) with another 5 patients being hospitalized for unrelated reasons.

Conclusion

Our medical center instituted an ASP led practice of closely monitoring and directing care with the local home health agencies due to concerns about patient safety. In doing so, we have realized a low rate of complications and an ability to manage the majority while remaining as an outpatient, with the exceptions of CVC-related complications and encephalopathy. Our data supports the center’s efforts and choice to dedicate resources to improving this increasingly popular treatment.

Disclosures

All authors: No reported disclosures.
A Little Bit of Dalba Goes a Long Way: Dalbavancin Use in a Vulnerable Patient Population
Authors: Bryson-Cahn Chloe , Beieler Alison , Chan Jeannie , Senter Steve , Harrington Robert , Dhanireddy Shireesha
Published: October 2017

Background

Serious staphylococcal infections require prolonged courses of intravenous (IV) antibiotics. Weekly IV dalbavancin is an alternative to more frequent IV antimicrobial dosing for homeless patients or persons who inject drugs (PWID), for whom creating a treatment plan can be challenging. We examined the clinical outcomes in patients who were treated with dalbavancin compared with a similar population treated with alternative antibiotics.

Methods

We identified 18 patients who received dalbavancin from June 1, 2015 to December 31, 2016 using pharmacy records and 89 patients receiving IV antibiotics for similar infections treated at Harborview Medical Center from January 1, 2015 to May 31, 2015, before dalbavancin was available. Medical records were reviewed, and patient demographics, length of stay (LOS), readmission, and outcomes were abstracted using REDCap, linked to the University of Washington’s Clinical Data Repository.

Results

Basic demographics in Table 1. The types of infections are in Figure 1. Clinical cure rates were similar between the two groups (Figure 2) although 21% and 28% of the patients were lost to follow-up in the pre and post dalbavancin period. Among the subgroup of PWID, those who received dalbavancin had higher rates of clinical cure (64.7% vs. 29.4%, P = 0.01), a trend toward decreased LOS (11.4 ± 5.8 vs. 20.2 ± 15.1 days, P = 0.04), and fewer 30-day readmissions (0% vs. 29.4%, P = 0.02) (Figure 2). Fewer PWID in the dalbavancin group were lost to follow-up (23.5% vs. 70.6%).

Conclusion

Patients treated with dalbavancin had similar outcomes compared with patients treated in the pre-dalbavancin time period. Among PWID, dalbavancin use led to significantly improved outcomes including a higher clinical cure rate, lower readmission rate, and shorter hospital LOS, which offset the cost of the drug. Dalbavancin is an option for the treatment of serious staphylococcal infections in selected patients.

Disclosures

All authors: No reported disclosures.
Injection Drug Use and Infectious Disease Practice: A National Provider Survey
Authors: Rapoport Alison B , Beekmann Susan E , Polgreen Philip M , Rowley Christopher F
Published: October 2017

Background

The opioid epidemic has swept across the U.S. at a staggering rate, with an estimated half million to one million persons injecting drugs annually. Rates of hospitalization for injection drug use (IDU)-related infection have risen precipitously, comprising an escalating proportion of infectious diseases provider volume in highly impacted regions.

Methods

In March 2017, the Emerging Infections Network surveyed their national network of infectious diseases (ID) physicians to evaluate perspectives relating to the care of persons who inject drugs (PWID), including the frequency of, and management strategies for, IDU-related infection, the availability of addiction services, and the evolving role of ID physicians in the management of addiction.

Results

Over half (53%; N = 672) of 1,276 members with an adult ID practice participated; 78% (n = 526) reported treating PWID. Of 526 respondents, 464 (88%) reported seeing ≥1 patient per month with an IDU-related infection; 228 (43%) reported ≥6 per month. In the past year, 79% of respondents reported the majority of IDU-related infections seen required ≥2 weeks of parenteral therapy and reported frequently encountering skin and soft-tissue infections (61%), bacteremia/fungemia (53%), and endocarditis (50%). Strategies most commonly employed for management of prolonged parenteral antibiotic therapy included: completion of entire course on inpatient unit (by 41%) and transfer to supervised facility for completion (35%). Only 35% of respondents agree/strongly agree their health system offers comprehensive treatment of substance use disorders (N = 181). Though nearly half of respondents felt that ID providers should actively manage substance use disorders (46%; N = 241), only 3% reported being waivered to prescribe buprenorphine for treatment of opioid use disorder.

Conclusion

The majority of infectious diseases physicians frequently care for PWID with serious infections. There is significant diversity amongst providers with regards to the availability of comprehensive addiction services as well as perceptions regarding the role providers should play in the management of addiction. Guidelines for the management of serious infections and concurrent addiction in the midst of the escalating national opioid crisis should be considered.

Disclosures

All authors: No reported disclosures.
Antibiotic Allergies – Is De-labeling Based on Clinical History Feasible?
Authors: Torda Adrienne , Chan Victor
Published: October 2017

Background

Up to 25% of patients admitted to hospital have an antibiotic allergy label (AAL), most of which are towards penicillin. However, up to 90% of patients who claim to be allergic to penicillin are actually able to tolerate them1. Whilst skin testing is safe and efficacious in de-labeling patients with a penicillin allergy label, it is usually not widely available. Therefore, we investigated the feasibility of de-labeling based solely upon clinical grounds. Quality of allergy documentation and subsequent antibiotic use was also assessed.

Methods

This was a cross-sectional study assessing all patients admitted to a tertiary referral teaching hospital over a 5-month period in 2016. All newly admitted patients were prospectively screened for the presence of an antibiotic allergy documented in their electronic medical record. Unless unable to participate, patients were interviewed regarding the detailed nature of their antibiotic allergy. Information regarding allergy documentation, medical condition and antibiotic use was obtained from medical records.

Results

3855 patients were screened, 553 (14.35%) had an AAL, and 352 were interviewed. There were 426 allergies, 276 (64.8%) towards a penicillin. Only 52% of patients had a convincing history consistent with antibiotic allergy, and 48% of these were mild cutaneous reactions. It was felt that de-labeling and direct re-challenge would be relatively safe in 70% (298/42) of AALs (if the mild cutaneous allergic group were included). In patients who were prescribed antibiotics during study admission, 25.6% (41/160) of antibiotic prescriptions in our cohort were found to be inappropriate in patients with AALs.

Conclusion

Direct re-challenge based upon clinical grounds appears to be a feasible clinical option in many patients with AALs and would allow de-labeling of these patients. The major barriers continue to be patient acceptance and risk of severe adverse reactions. Our study also found that major improvements could be made in the specific documentation of allergy and also in selection of guideline-recommended alternate antibiotics.

1. Joint Task Force on Practice Parameters. Drug Allergy: An Updated Practice Parameter. Ann Allergy Asthma Immunol. 2010; 105(4): p. 259–273.

Disclosures

All authors: No reported disclosures.