bluuebunny/crossref_metadata_2025_split huggingface dataset:
2647. Influenza Treatment Rates in UK Primary Care Settings: Real-World Data Analysis of the CPRD, 2003–2018
Authors: Chawla Devika , Dayal Parul , Kuhlbusch Klaus , Moawad Dalia , Wallick Chris , Keebler Daniel 
Published: October 2019

Abstract

Background
Influenza remains a significant public health burden, resulting in serious morbidity and mortality globally. The National Institute for Health and Care Excellence (NICE) recommends treatment with antivirals for a broad range of high-risk influenza cases; however, anecdotal reports suggest treatment rates in the United Kingdom remain low. Real-world evidence on influenza treatment patterns in this region is limited. We therefore sought to investigate the proportion of influenza cases presenting to UK primary care facilities that receive antiviral treatment.

Methods
Data were obtained from the Clinical Practice Research Datalink (CPRD), a database of medical records from 674 primary care facilities in the UK. Cases were eligible for study inclusion if a diagnosis code for influenza or influenza-like illness (ILI) occurred between 1 January 2003 and 31 December 2018, and the medical record had sufficient data quality. Treatment was defined as prescription of an antiviral (oseltamivir, zanamivir, peramivir, or amantadine) within ±10 days of diagnosis. We examined (1) treatment rates, overall and by study year to understand time trends, (2) distribution of antiviral types prescribed, and (3) patient characteristics across treatment status.

Results
Of the 116,923 cases of influenza that met study inclusion criteria, 10,923 (9.3%) were treated with an antiviral. Treatment rates varied by study year, ranging from <1.0% in 2004 to 24.0% in 2009. The most recent study year (2018) had a treatment rate of 11.2%. Oseltamivir was the most frequent antiviral prescribed, followed by zanamivir. Treated cases of influenza were younger and more likely to be female compared with untreated cases.

Conclusion
We evaluated real-world estimates of influenza treatment rates over a 16-year period in UK primary care settings, where anecdotal reports suggested low treatment rates. Consistent with these reports, we observed low treatment rates, likely due in part to inclusion criteria and clinical guidelines specifying treatment only for high-risk cases. Subsequent analyses will investigate treatment patterns and patient characteristics in high-risk vs. low-risk cases to provide additional context for observed treatment rates.

Disclosures
All authors: No reported disclosures.
2649. Measles-Containing Vaccination Resulted in a Balanced Cytokine Profile Without Evidence of Immunosuppression in Healthy 12-Month-Old Children
Authors: Gans Hayley , Wang Weiqi , Rosenberg-Hasson Yael , Zerbo Ousseny , Modaressi Sharareh , Goddard Kristin , Lewis Ned , Bok Karin , Klein Nicola 
Published: October 2019

Abstract

Background
Measles virus infection results in immune activation, viral clearance and lifelong immunity. In addition, there is an immunosuppressive state defined by type 2 skewing of CD4+ T‐cell cytokine production and induction of regulatory T cells with reduced dendritic cell (DC) activation in the recovery phase. Studies following measles immunization show conflicting immune profiles. To more robustly interrogate and define specific functional cytokine profiles, this study evaluated cytokine profiles in 12-month old infants before and after primary MMR vaccination.

Methods
Cytokine profiles using luminex assay (62-plex; eBioscience) were measured in 65 infants before and 42 days after MMR vaccination administered at 12 months of age as part of a randomized clinical trial. Mean cytokine percentages of children with increased or decreased concentrations of each cytokine in the post sample compared with the levels in the pre sample were evaluated using Student’s t-test. Cytokines were arranged into dominant CD4+ T-cell type, Th1, Th2, and T regulatory (Treg) and those produced by DC.

Results
No dominant cytokine pattern emerged following measles immunization, with a balanced profile. The mean percentage of children with increased and decreased concentrations (pg/mL) of signature CD 4+ T-cell Th1 (tumor necrosis factor alpha [TNFa], interferon gamma [IFNg]), Th2 (Interleukin [IL] IL5, IL4, IL13), Treg (IL10, transforming growth factor-β TCFb) and DC (IL12P40 and IL12P70) cytokines were equivalent when measured at 42 days after MMR vaccine compared with levels before vaccine (Table 1) (P ≥ 0.05 for all comparisons).

Conclusion
In contrast to data demonstrating an immune suppression profile following measles disease, measles-containing vaccine did not suppress Th1 CD4+ T-cell and DC cytokines or promote Th2 and Treg CD4+ T-cell cytokines measured 42 days after vaccination. The cytokine profile represents one of balance and homeostasis. This study supports the data that show measles vaccine does not cause immunosuppression in healthy infants.

Disclosures
All authors: No reported disclosures.
2652. Cytomegalovirus Meningoencephalitis: A Comparison to Other Viral CNS Infections
Authors: Pankow Stephanie , Masayuki Nigo , Hasbun Rodrigo 
Published: October 2019

Abstract

Background
Cytomegalovirus (CMV) is a rare cause of meningoencephalitis (ME) with clinical data limited to case reports.

Methods
Retrospective observational study of all viral central nervous system (CNS) infections identified in 17 hospitals in the Greater Houston area from 2000 to 2017. CMV, herpes simplex virus (HSV), varicella zoster virus (VZV), and enterovirus were all identified by a positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) and all arboviruses were identified by serology.

Results
A total of 361 patients with viral CNS infections were identified: CMV (n = 33), enterovirus (n = 147), herpes simplex virus (n = 83), varicella zoster virus (n = 28), and arbovirus (n = 70). CMV ME occurred more frequently in immunosuppressed patients [e.g., Acquired Immune Deficiency Syndrome (AIDS)], had more hypoglycorrhachia (59%), and had worse clinical outcomes (61%) as compared with those with HSV, enterovirus, VZV and arboviruses. Furthermore, CMV ME had more altered mental status than enterovirus and HSV and had lower CSF pleocytosis compared with HSV. Additionally, CMV ME had higher CSF protein levels than enteroviral infections and had less CSF lymphocytosis than HSV and VZV.

Conclusion
CMV meningoencephalitis is seen more frequently in immunosuppressed patients (e.g., AIDS), is associated with more hypoglycorrhachia and have worse clinical outcomes compared with other viral CNS pathogens.

Disclosures
All authors: No reported disclosures.
2666. De-escalation of Broad-Spectrum Antibiotics in Hematopoietic Stem Cell Transplant Patients During Initial Episode of Febrile Neutropenia
Authors: Rearigh Lindsey , Stohs Erica J , Freifeld Alison , Zimmer Andrea 
Published: October 2019

Abstract

Background
Febrile neutropenia (FN) is a common and serious complication in patients undergoing hematopoietic stem cell transplant (HSCT). Typically, broad-spectrum antibiotics (BSA) are promptly initiated with controversy on timing of de-escalation. ECIL 2013 guidelines suggest de-escalation after 72 hours if the patient is infection free and afebrile for at least 48 hours. Conversely, the 2011 IDSA recommends continuing BSA in patients who defervesce until absolute neutrophil count (ANC) recovery. In 2014, our center’s practice changed to early de-escalation and we sought to compare outcomes between the two practices.

Methods
We retrospectively analyzed patients who underwent a HSCT in 2013 and 2017 with an episode of FN and negative infectious work up. The standard care group (SCG) were continued on BSA until ANC recovery. The early de-escalation group (EDG) de-escalated to fluoroquinolone prophylaxis at least 24 hours prior to ANC recovery after the patient was fever free for 48 hours. The primary end-point was duration of BSA. Secondary endpoints included 30-day mortality, re-hospitalization and length of stay (LOS) from FN. Median values were compared with the Mann–Whitney test.

Results
Among 229 HSCT patients, 155 (68%) developed FN post-transplant and of those 97 (63%) were without infection (13 EDG and 84 SCG). Initial FN duration of BSA was less in the EDG (3.09 days vs. 4.69 days, P = 0.069). Total antibiotic free days to 30 day follow-up were similar (EDG 24.08 vs SCG 25.19, P = 0.81). Duration of neutropenia was less in the SCG with 7.99 days compared with 11.69 days in the EDG (P = 0.007), but duration of initial fever was less in the EDG (2.55 days vs. 3.33 days, P = 0.023). 30 day mortality was 0% in both groups. Rates of re-hospitalization within 30 days were approximately the same (7.1% vs. 7.6%). LOS from FN was not significantly different with 6.68 days in SCG and 7.75 days in EDG (P = 0.140). More new bacterial infections were identified within 30 days of FN in the SCG than the EDG (10.7% vs. 7.6%).

Conclusion
Early BSA de-escalation resulted in no significant difference in LOS from FN and fewer days of BSA with 30-day mortality and re-hospitalization rates similar. This data suggest de-escalating BSA prior to ANC recovery is likely safe and leads to less BSA exposure, but more multi-center data are needed.

Disclosures
All authors: No reported disclosures.
2681. Outcomes Related to Respiratory Viral Infections in Cancer Patients on PD-1 Inhibitors
Authors: Khawaja Fareed , Batista Marjorie V , Chaftari Patrick , Tayar Jean , Chemaly Roy F , Chemaly Roy F 
Published: October 2019

Abstract

Background
The PD-1 inhibitors or check point inhibitors (CPI) are commonly used for the treatment of many solid tumors (ST) and hematological malignancies (HM). By blocking PD-1 in fatigued T cells, an increase in viral clearance may be noted as evidenced in cases of JC virus. Our objective was to assess the outcomes related to cancer patients with microbiologically documented acute respiratory viral infections while on CPI.

Methods
All patients who were infected with either influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), and human metapneumovirus (HMPV) from 9/2016 to 6/2018 with prior or concurrent CPI therapy were included in this study. Demographics and clinical data were collected retrospectively. Comparisons were done between patients with concurrent (group 1) or prior (group 2) CPI therapy.

Results
A total of 92 cancer patients were identified and of those, 50 patients (54%) were on concurrent CPI therapy at the time of infection. Most patients had ST, mainly non-small cell lung cancer, and most were predominantly infected with Influenza (Figures 1 and 2). Side effects-related to CPI therapy and steroid use prior to infection were uncommon (13%). When compared with group 2, patients in group 1 had a trend toward less lower respiratory tract infections (24% vs. 40%, P = 0.11), decreased median length of stay (3 vs. 8 days, P = 0.1125) and lower 30-day mortality (4% vs. 12%, P = 0.2396).

Conclusion
Our data demonstrated trends toward improved outcomes in patients with respiratory viral infections on concurrent CPI therapy. Whether improved outcomes are related to enhanced immune responses to these viral infections need to be determined in a larger prospective observational cohort of patients.

Disclosures
Roy F. Chemaly, MD, MPH, FACP, FIDSA, Chimerix: Advisory Board, Research Grant; Clinigen: Advisory Board; Merck: Advisory Board, Consultant, Grant/Research Support, Research Grant, Speaker’s Bureau; Oxford immunotec: Consultant, Grant/Research Support; Shire: Research Grant, Speaker’s Bureau; Viracor: Grant/Research Support.
161. Evaluating the Predictive Value of Blood Culture Bottle Reporting for Coagulase Negative Staphylococci-Positive Cultures: Assessing Contamination vs. True Bacteremia
Authors: Bailey Pamela , Doern Christopher 
Published: October 2019

Abstract

Background
Coagulase-negative staphylococci (CoNS) are common blood culture (BCx) contaminants, but can also be causes of true blood stream infection (BSI). As a result, the clinical interpretation of CoNS positive BCx poses a significant challenge for providers and drives unnecessary antibiotic use, extended lengths of stay, and increased hospital costs. Despite these challenges, little is known about whether the number of positive BCx bottles within a set can be used to predict contamination vs. true BSI.

Methods
This study was conducted in an 865-bed tertiary care academic medical center in Richmond, VA. A retrospective chart review of CoNS-positive BCx from October to December 2018 was performed. Data collection included patient demographics, number of positive bottles within a set (i.e., were 1 or 2 bottles positive), care setting, antibiotic use, clinical judgement of contamination, and additional workup following the positive BCx result. Polymicrobic BCx were excluded.

Results
50 patients (mean age 58.2 years, 60% male) with CoNS-positive BCx were included in this study. Forty (80%) of the cultures had only 1 of 2 BCx bottles positive within a set. 10 (20%) were positive from both bottles in the set. All patients were drawn in the Emergency Department and 90% were subsequently admitted to the hospital. Upon chart review, 47 (94%) and 3 (6%) of cultures were considered to be contaminants and real BSI, respectively. Of those judged to be contaminants, 10 (20%) were positive in both bottles within a set, and thus falsely suggested true BSI. Of the 3 judged to be true BSI, 2 (66%) were positive in 1 out of 2 bottles, and thus falsely suggested contamination.
42 (84%) patients had repeat BCx drawn following the initial positive culture, and 26 (52%) were continued on IV antibiotics. Forty (80%) of the cultures were judged contaminants by the primary medical service, and 77% stopped antibiotics (20/26) when CoNS was identified.

Conclusion
These data show that reporting the number of bottles which are positive within a set provides misleading information and should not be used to determine whether a culture result represents contamination or true BSI.

Disclosures
All authors: No reported disclosures.
2702. Infants Vaccinated with a Fully-Liquid DTaP-IPV-Hib-HepB Vaccine Are Protected During the High-Risk Period for Haemophilus Influenzae Type B Disease
Authors: Wilck Marissa B , Xu Jin , Stek Jon E , Lee Andrew W 
Published: October 2019

Abstract

Background
DTaP-IPV-Hib-HepB is a fully-liquid, combination vaccine (Vaxelis™) approved for vaccination in infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b (Hib). Safety and immunogenicity were evaluated in 4 Phase III, randomized, active-comparator controlled clinical trials (Protocols 005 and 006 in the US [Control: PENTACEL™] and Protocols 007 and 008 in the EU [Control: INFANRIX™ hexa]). The vaccine, studied in >6,800 children, has an acceptable safety profile generally similar to that of control vaccines (Xu, PIDJ, 2019; 38:439–43). DTaP-IPV-Hib-HepB includes polyribosylribitol phosphate (PRP) conjugated to outer membrane protein complex of Neisseria meningitidis (OMPC) that elicits a rapid response to Hib.

Methods
Data from these studies provide a summary of the anti-PRP responses of DTaP-IPV-Hib-HepB compared with Control.

Results
After the infant series, the percentage of participants who achieved short-term and long-term protective antibody thresholds for PRP (i.e., anti-PRP titer ≥0.15 μg/mL and ≥1.0 μg/mL, respectively) were higher in DTaP-IPV-Hib-HepB recipients compared with Control. A high level of protective responses (96.6% ≥0.15 μg/mL and 72.9% ≥1.0 μg/mL) were seen after the second dose in the 008 study of the 2 infant series followed by toddler dose hexavalent vaccination schedule (2 + 1). Across all 4 studies, anti-PRP titers were higher in DTaP-IPV-Hib-HepB recipients (91.4% ≥0.15 μg/mL and 46.8% ≥1.0 μg/mL) when compared with Control (63.4% ≥0.15 μg/mL and 17.1% ≥1.0 μg/mL) at the pre-Toddler dose (i.e., prior to the administration of the Toddler dose in the second year of life, between 11–15 months of age). One month after the toddler dose, high levels of anti-PRP titers were achieved in both DTaP-IPV-Hib-HepB recipients (99.8% ≥0.15 μg/mL and 96.6% ≥1.0 μg/mL) and Control (99.5% ≥0.15 μg/mL and 94.9% ≥1.0 μg/mL).

Conclusion
These results support that DTaP-IPV-Hib-HepB induces an early Hib response in the first 6 months of life that is sustained until the booster dose is administered in the second year of life. Thus, a high percentage of infants vaccinated with DTaP-IPV-Hib-HepB are protected during the high-risk period for Hib disease.

Disclosures
All authors: No reported disclosures.
2721. US States’ Policies for Meningococcal Vaccination vs. Disease Epidemiology
Authors: Srivastava Amit , Alderfer Justine 
Published: October 2019

Abstract

Background
Serogroup B (MenB) is the leading cause of invasive meningococcal disease (IMD) cases in the United States, including 69% of cases among 16- to 23-year-olds. College students have 3.5 times greater MenB risk vs noncollege individuals, and MenB caused all college IMD outbreaks between 2011 and 2019. For healthy adolescents, the Advisory Committee on Immunization Practices (ACIP) recommends routine MenACWY vaccination at 11 and 16 years and MenB vaccination based on individual clinical decision-making, preferably at 16‒18 years (Figure 1A, B). Given the recent shift in disease epidemiology, we investigated whether current state policies also shifted to help protect adolescents against all 5 meningococcal serogroups.

Methods
We researched requirements for meningococcal vaccination using state public health websites and national stakeholder materials (e.g., Immunization Action Coalition and their state chapters). Data as of November 2018 were compiled by vaccine type, age, and school/college requirements.

Results
Forty-five states and Washington DC require either meningococcal vaccination and/or vaccine education for school attendance (grades 6–12) and for college attendance. Thirty-one states require a MenACWY primary dose (at 11 years), of which 16 states also require the booster dose at 16 years (Table 1, Figure 1C). One state requires MenB vaccination at 16–18 years. Of the 8 states that experienced college MenB outbreaks between 2013 and February 2019, all require vaccination or education for MenACWY but not MenB (Table 2). These differences in state requirements may underlie the reported adolescent vaccination coverage rates for MenACWY (85% for ≥ 1 dose, 44% for ≥ 2 doses) and MenB (14.5% for ≥ 1 dose of multidose series) vaccines, and additional reasons may be the efficiency of school-based vaccination programs, strength of the 11-year immunization platform, the more recent availability of MenB vs MenACWY vaccines, and disparate ACIP recommendations for these vaccines.

Conclusion
State vaccination requirements have helped catalyze MenACWY vaccine impact. Tailoring new requirements to the current epidemiology can help quell MenB disease and ensure that US adolescents are fully protected against meningococcal disease.
Funding: Pfizer

Disclosures
All authors: No reported disclosures.
2736. Insurance Disparity in United States Cancer Survivors’ Influenza Vaccination Rates: A Trend Study from NHIS 2005–2017
Authors: Zheng Xin , Jiang Changchuan 
Published: October 2019

Abstract

Background
Patients with underlying cancer often have suppressed immunity from disease process and cancer therapy, making this population particularly vulnerable to influenza. Few studies have investigated the overall flu vaccination rates; however, little is known regarding the trend of vaccination rates in US cancer survivors and how it varied by individuals’ insurance coverage.

Methods
We conducted a retrospective cross-sectional study to evaluate the temporal trend of flu vaccination rates using the National Health Interview Survey from 2005 through 2017. Adult cancer survivors (n = 24,381) were included in the analysis. The outcomes were self-reported flu vaccination during the past 12 months with either inactivated or live attenuated nasal vaccine. Insurance coverage was categorized into private (age ≤65), other coverage (age ≤65), uninsured (age ≤65), Medicare and private (age > 65), and other coverage (age > 65). We combined every 2 years data to improve statistical power in the subgroup analysis. Weighted analyses were performed with SAS 9.4 to account for the complex design and NCI-Joinpoint 4.7 was used for joinpoint regression in the trend analysis.

Results
The overall cancer survivors’ flu vaccination rates improved from 45% in 2005 to 63% in 2017, whereas the cancer-free group improved from 18% in 2005 to 41% in 2017. With cancer survivors, influenza vaccination rates varied remarkably by insurance status (P < 0.001). Elderly survivors (age 65+) with any type of insurance consistently had higher flu vaccination rates than survivors younger than 65 (averaging 70% vs. 40%). For cancer patients age 65 or younger, whether insured or not, the overall flu vaccination rates had improved since 2005. However, for the subgroup who had coverage but not with private insurance, the vaccination rates had been declining since 2012 (50% in 2012/2013 to 45% in 2016/2017).

Conclusion
Despite the overall increase of flu vaccination rates in both cancer survivors and cancer-free participants since 2005, the growth rate has plateaued since 2015. This is likely related to shifts in healthcare law on the national level. Such impact is particularly significant in cancer patients who are younger and do not have private insurance coverage. Such vulnerable and underserved population will need more resources to help improve their influenza vaccination rate.

Disclosures
All authors: No reported disclosures.