bluuebunny/crossref_metadata_2025 huggingface dataset:
2686. strong>Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) with Fever and Neutropenia (FN): Viridans Group Streptococcus Emerges as an Important Pathogen
Authors: Stohs Erica , Zimmer Andrea , Fey Paul , Handke Luke D , Zhang Yuning , Arnold Christopher , Baddley John W , Chandrasekar Pranatharthi , Boghdadly Zeinab El , Gomez Carlos A , Maziarz Eileen K , Montoya Jose G , Pergam Steven A , Rolston Kenneth , Satlin Michael J , Satyanarayana Gowri , Shoham Shmuel , Strasfeld Lynne , Taplitz Randy , Walsh Thomas J , Young Jo-Anne H , Freifeld Alison
Published: October 2019

Background

In this prospective nation-wide survey of bloodstream isolates associated with first episode of FN in high-risk cancer patients from 14 US cancer centers (December 2016 and June 2018), viridans group Streptococci (VGS) were the most common Gram-positive isolate. We sought to clinically and microbiologically characterize VGS bloodstream infections (BSI).

Methods

Among 343 patients,we compared 90 with VGS vs 253 with non-VGS BSI. Minimum inhibitory concentrations for blood culture isolates were determined by broth dilution for selected agents at our reference microbiology laboratory (UNMC). Clinical data were electronically captured in RedCap, including local site isolate identification and confirmatory reference lab identification via MALDI. Categorical and continuous variables were assessed via chi-square and Mann–Whitney U tests, respectively.

Results

Ninety-two VGS isolates were identified among 90 FN patients, representing 27% of all BSI isolates. S. mitis or oralis comprised 64 (70%) of VGS. There were no differences between age, sex, and primary diagnosis (50% with AML) among the 2 groups; 1/3 were HSCT recipients. Fluoroquinolone prophylaxis was used in 64 (71%) vs. 139 (55%), P < 0.01, in VGS vs non-VGS groups. Critical illness composite (new need for pressor(s), mechanical ventilation or death within 30 days) was 6 (7%) vs. 44 (17%), P = 0.01, in the VGS vs non-VGS groups. Figure 1 displays an overview of antibiotic susceptibilities for 79 testable isolates. VGS susceptibilities to levofloxacin, penicillin, and ceftriaxone were 39%, 47%, and 94%, respectively.

Conclusion

VGS are common pathogens in FN patients. Prior fluoroquinolone prophylaxis use may be a risk factor. VGS BSI was not associated with increased critical illness compared with non-VGS. Finally, assuming ceftriaxone susceptibility confers that of cefepime, >90% of VGS are susceptible to empiric FN cefepime regimens.

Disclosures

All authors: No reported disclosures.
2688. The Clinical Impact of Early De-escalation of Broad-Spectrum Antibiotics in Acute Myeloid Leukemia Patients with Febrile Neutropenia
Authors: Davis Matthew , Afifi Salma , McManus Dayna , Topal Jeffrey E
Published: October 2019

Background

In patients with febrile neutropenia (FN) the initiation of broad-spectrum antibiotics (BSA), an anti-pseudomonal agent +/− vancomycin, is recommended by national guidelines. BSA should be continued until absolute neutrophil count (ANC) recovery (ANC > 500 cells/mm3). With increasing antimicrobial resistance, clinicians are reassessing the need to continue BSA until count recovery; new data are emerging that patients may be able to have their BSA de-escalated if stable and afebrile. At our institution, some patients are de-escalated from BSA to a fluoroquinolone before ANC recovery and others are continued on BSA. The purpose of this study was to evaluate the efficacy and safety of early de-escalation compared with the standard of care.

Methods

We retrospectively reviewed acute myeloid leukemia patients receiving induction chemotherapy who developed FN while at Yale New Haven Hospital from March 2013 to August 2018. Patients were excluded if they developed a culture documented infection, received incomplete or multiple induction chemotherapy treatments, or died from underlying disease during hospitalization. The primary outcome was recurrent fever during admission and secondary outcomes included incidence of breakthrough infections (BI), duration of hospital stay, early discharge (discharge before ANC recovery), duration of BSA, and readmission within 7 days of discharge.

Results

A total of 210 patients were evaluated and 91 patients were included (de-escalation, n = 45; BSA, n = 46). Baseline characteristics are noted in Table 1. There was no statistical difference in rate of recurrent fever in patients who were de-escalated from BSA compared with those that were continued (P = 0.05). De-escalated patients had a shorter duration of BSA therapy (P < 0.05), earlier discharge (P = 0.05) and no difference in readmission rates (P = 0.39) (Table 2). There was no difference in rate of BI between both groups and all BI were bacteremias. (Table 3) No patients who experienced a BI died from infection.

Conclusion

The results of this study revealed no difference in the primary outcome of recurrent fever between the BSA and de-escalation groups. De-escalation led to a reduced duration of BSA and facilitated earlier discharge without increasing readmission rates and BI.

Disclosures

All authors: No reported disclosures.
2692. Comparison of Demographics and Risk factors Between Strongyloides stercoralis Seropositive and Seronegative Solid-Organ Transplant Candidates: Experience from a Tertiary Acute Care Center in Florida
Authors: Perez-Lopez Carlos J , Alrabaa Sally , Aslam Sadaf , Teo Greg Matthew E , Kim Teayoung , Reljic Tea
Published: October 2019

Background

Strongyloides stercoralis is a nematode endemic to the tropical and subtropical regions. In the United States, it is mostly found at southeastern states. Most infections are asymptomatic but disseminated and fatal infections have been reported in immunocompromised patients. At our institution, universal screening through Strongyloides antibody detection in serum among solid-organ transplant candidates began since 2010 and all seropositive candidates are treated before transplantation. We previously determined our incidence to be about 5%. The aim of this study was to determine demographic characteristics and risk factors that can be used for more cost-effective targeted screening.

Methods

We performed a retrospective cohort study of patients who underwent transplant evaluation from 2014 to 2016. A total of 228 charts were reviewed for Strongyloides serology status, eosinophilia, demographics and risk factors. Chi-square and Fisher exact tests were used to do a comparative analysis between Strongyloides seropositive and seronegative cohorts.

Results

We identified 113 seropositive (SP) patients and 115 seronegative (SN) patients. There were more males in the seropositive group (79%) compared with seronegative group (62%) (P = 0.005). Caucasians predominated in both groups (SP 71% vs. SN 57%; P = 0.286). No significant difference was found between both groups with regards to occupation with soil or water contact (SP 38% vs. SN 30%; P = 0.281), birthplace outside USA or travel outside of United States (SP 31% vs. SN 36%; P = 0.732). Eosinophilia occurred less in the seropositive group compared with the seronegative group (SP 16% vs. SN 30%; P = 0.030).

Conclusion

The study did not find any statistically significant difference in the demographic characteristics or risk factors that can be used for prediction of Strongyloides seropositivity among solid-organ transplant candidates. Hence, our institution will continue universal screening for Strongyloides stercoralis for all our transplant candidates. Our findings further question donor screening for Strongyloides that uses a similar questionnaire which may not be reliable to identify those infected with this parasite. This would put recipients at risk for a donor-transmitted infection.

Disclosures

All authors: No reported disclosures.
2695. Pneumocystis jirovecii Pneumonia in the Era of Effective Prophylaxis Following Hematopoietic Stem Cell Transplant
Authors: Drelick Alexander Christian , Kodiyanplakkal Priya , Plate Markus , Satlin Michael J , Soave Rosemary , Shore Tsiporah , Besien Koen Van , Small Catherine , Walsh Thomas J
Published: October 2019

Background

Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used.

Methods

We performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology.

Results

1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively.

Conclusion

PJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid.

Disclosures

All authors: No reported disclosures.
2699. Pneumococcal Vaccination During Chemotherapy in Children Treated for Acute Lymphoblastic Leukemia
Authors: Dorval Sarah , Coïc Léna , Blais Denis , Leclerc Jean-Marie , Laverdière Caroline , Ovetchkine Philippe , Tapiéro Bruce
Published: October 2019

Background

Children undergoing therapy for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). Immunization with conjugated vaccines following chemotherapy is recommended for pediatric patients. In an attempt to provide an earlier protection against invasive pneumococcal infection, we aimed to assess immunity to S. pneumoniae among children vaccinated during chemotherapy for ALL.

Methods

We retrospectively analyzed the rate of seroprotection among ALL children treated in our institution in accordance with the DFCI ALL Consortium protocol between 2007 and 2014. A pneumococcal conjugate vaccine (PCV) booster was given to all subjects after the end of chemotherapy (groups 1 and 2). In group 2, a PCV dose was also administered during the maintenance phase. Clinical characteristics as well as individual immunization records were collected from our local immunization database. All children were up to date with their vaccination schedule at diagnosis. Serum samples were obtained on a routine follow-up visit, after the end of chemotherapy and after the PCV vaccine booster to measure serotype-specific IgG pneumococcal antibodies. Antibody level ≥0.35µg/mL was considered protective. Patients with seroprotective antibodies level for ≥ 50% of serotypes contained in vaccines were defined as seroprotected.

Results

62 children [34 girls (54.8%)] were included in the analysis. Median age at diagnosis was 45 months (range:12–160).

At the end of chemotherapy, 34.2% of children in group 1 (13/38) and 79.2% in group 2 (19/24) were seroprotected (P < 0.01). Median interval of time between the end of chemotherapy and the PCV booster vaccination was 6 months (range: 2–64 months). After PCV-13 booster, the rate of seroprotection raised to 100% (38/38) in group 1 and 91.7% in group 2 (22/24).

Conclusion

Rates of pneumococcal seroprotected children treated for ALL are low at the end of chemotherapy. However, PCV booster during chemotherapy could be useful to increase the level of seroprotection and shorten the period of susceptibility to IPD. After chemotherapy for ALL, children benefit from a PCV booster to enhance seroprotection.

Disclosures

All authors: No reported disclosures.
163. Infective Endocarditis in Qatar: Risk Factors, Clinical Characteristics, Microbiology, and Outcomes
Authors: Zaqout Ahmed , Mohammed Shaban , Thapur Maliha , Al Soub Hussam , Almaslamani Muna , Al Khal Abdullatif , Omrani Ali S
Published: October 2019

Background

Infective endocarditis (IE) is a serious and life-threatening disease. The aim of the study is to describe the epidemiology, clinical characteristics and outcomes of patients with IE in Qatar.

Methods

Patients were identified from the electronic records of Hamad Medical Corporation hospitals, the national referral center for the State of Qatar. Those aged ≥18 years with Duke Criteria-based diagnosis of IE during the period from January 2015 to September 2017 were included. Data were analyzed using STATA software Version 15.

Results

Fifty-seven cases were included, of which 70% were males. Mean age was 51 years (± 16.8). Eleven (19%) were in association with prosthetic valves and 6 (11%) with implantable cardiac devices (Table 1). Fever (84%), dyspnea (46%) and heart failure were the commonest presentations. The majority of patients had preexisting valvular heart disease or intra-cardiac devices (Table 1). Skin infections (10, 18%) were the most prevalent portals of infection, followed by venous catheters, recent valve surgery and implantable cardiac devices (Table 1). Staphylococcus species were implicated in 19 (34%) and Streptococcaceae in 9 (16%); whereas 21 (37%) were culture-negative (Table 2). Left-side IE (49, 86%) was predominant. Acute kidney injury (AKI) (17, 30%) and heart failure (11, 19%) were common complications. The most frequently used treatment regimens included glycopeptides or Β-lactams (Table 2). Only 9 (16%) patients underwent surgical intervention. Fourteen (25%) patients died of any cause before hospital discharge. Logistic regression analysis identified septic shock and AKI as the only risk factors independently associated with in-hospital mortality (Table 3).

Conclusion

Skin infections are an important risk for IE in Qatar. The majority of patients with IE have preexisting cardiac conditions. Staphylococci are the commonest confirmed bacterial etiology of IE in Qatar, but nearly one-third of cases are culture-negative. Only a small proportion of patients with IE undergo surgical intervention and overall mortality is high. The findings suggest that efforts should be directed toward improving IE prevention strategies in high-risk patients, encourage early microbiological investigations and improved medical and surgical management.

Disclosures

All authors: No reported disclosures.
2710. Novel Analytical Models for Pneumococcal Multiplex Opsonophagocytosis Assay Results from a Healthy Older Adult Population Vaccinated with PCV13
Authors: LaFon David , Kim Young , Nahm Moon H
Published: October 2019

Background

The multiplexed opsonophagocytosis assay (MOPA) measures killing of pneumococci by serum antibodies, and is the primary method for measuring pneumococcal antibodies in adults. However, pre-vaccine opsonic activity and vaccine response are highly variable among serotypes and individuals, and there are currently no criteria to define normal MOPA results.

Methods

We performed post-hoc analysis of data from n = 311 healthy, pneumococcal-vaccine naïve adults aged 55–74 who received 0.5 mL PCV13, and had MOPA performed for PCV13 serotypes (except serotype 3) at baseline, then on days 29 and 181 post-vaccine (Jackson et al. 2018, Vaccine). MOPA results (reported as opsonic index, or OI) were standardized using pneumococcal reference serum 007sp. Pairwise comparisons of proportions of undetectable baseline OI (≤ 4) between serotypes were performed using Pearson’s Chi-square. Immunogenicity (mean change in OI at day 29 post-PCV among samples with undetectable baseline OI) was compared between serotypes using one-way ANOVA. We then assigned a score based on cutoffs for pre-vaccine OI (cutoff 1, or C1) and fold-rise in OI at day 29 (cutoff 2, or C2) for each serotype, as shown in Figure 1. The sum of the scores for 12 serotypes was determined for each participant. We plotted the frequency distribution of total scores using different combinations of values for C1 and C2 to visually identify the optimal fit for the left-skewed distribution expected in a healthy population.

Results

Serotype 1 had the highest prevalence of undetectable OI at baseline (77.0%, P < 0.001), and serotype 19A had the lowest (8.8%, P < 0.001). Immunogenicity was highest for serotype 7F (mean change of 18354, P < 0.001 for all comparisons). For vaccine response analysis, C1 = 300 and C2 = 8 produced a left-skewed distribution (Figure 2). Using these cutoffs, the median total score was 7 and the 5th percentile score was −1.

Conclusion

Criteria for normal MOPA results can be developed for single-timepoint data, or using a scoring system for vaccine response data that integrates pre-vaccine OI and fold-rise in OI. Additional studies in healthy and disease populations are needed to further optimize diagnostic criteria for discriminating normal vs. abnormal results.

Disclosures

All authors: No reported disclosures.
164. Analysis of Adult, Hospitalized Patients With Carbapenem-resistant (CR) Gram-Negative Bloodstream Infections (GN-BSIs) due to Lactose Fermenters (LFs) and Non-lactose Fermenters (NLFs): Is There a Difference in Outcomes?
Authors: Lodise Thomas , Kanakamedala Hemanth , Hsu Wei-Chun , Cai Bin
Published: October 2019

Background

The deleterious consequences of BSIs due to CR-GN bacteria among hospitalized adult patients are well described in the literature. However, scant data exist that compares the baseline features and outcomes of patients with CR-GN-BSIs due to LFs relative to those caused by NLFs.

Methods

We performed a retrospective cohort analysis of consecutive hospitalized adult patients (age ≥18 years) in the Premier Healthcare Database (January 2014–June 2018) with GN-BSI due to select LFs (E. coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., and Serratia spp.) and NLFs (Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas spp.). Patients with a diagnosis of cystic fibrosis or who had both LF and NLF GNB on index BSI culture were excluded. Baseline demographics, medical history, comorbidities, hospitalization history, and outcomes were compared between patients with CR-GNB due to LFs and NLFs. Outcomes assessed included composite death (in-hospital death or discharge to hospice), in-hospital mortality, discharge to home, and hospital length of stay post index GNB-BSI culture collection.

Results

Of the 1749 patients with a CR-GNB-BSI due to an LF or NLF, 1505 met study criteria. Of the 1505, 418 (27.8%) were LFs and 1087 (72.2%) were NLFs. The most common LFs were Klebsiella spp. (55.7%) and Enterobacter spp. (25.7%), while Stenotrophomonas spp. (45.2%) was the most common NLF. Overall, groups were highly similar at baseline but patients with CR-GNB-BSIs due to an LF were slightly older and more likely to be in the ICU at index BSI culture collection (table). Outcomes were also comparable between patients with CR-GNB-BSIs due to LFs and NLFs but there were a few notable differences. Composite mortality was higher in patients with GNB-BSIs due to an LF and these patients were also less likely to be discharged home.

Conclusion

The findings indicate that CR-GNB-BSIs result in considerable morbidity and mortality irrespective of whether the GNB is an LF or NLF. One in five patients died during their hospitalization and less than half were discharged home. This highlights the need for better and more preventive and therapeutic strategies aimed at combating CR-GNB-BSIs.

Disclosures

All authors: No reported disclosures.
2714. Streptococcus pneumoniae Nasopharyngeal Carriage in Canadian Adults Hospitalized with Community-Acquired Pneumonia from 2010 to 2017
Authors: LeBlanc Jason J , ElSherif May , Lang Amanda L S , Gillis Hayley D , Ye Lingyun , MacKinnon-Cameron Donna , Ambrose Ardith , Hatchette Todd F , Martin Irene , Demczuk Walter , Andrew Melissa K , Boivin Guy , Bowie William , Green Karen , Johnstone Jennie , Loeb Mark , McCarthy Anne , McGeer Allison , Semret Makeda , Trottier Sylvie , Valiquette Louis , Webster Duncan , McNeil Shelly
Published: October 2019

Background

Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017.

Methods

Active surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs.

Results

Overall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B.

Conclusion

Monitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD.

Disclosures

All authors: No reported disclosures.
2715. Pneumococcal Community-Acquired Pneumonia Attributed to PCV13 Serotypes in Hospitalized Adults: Comparison of the 50–64 and 65+ Age Groups
Authors: LeBlanc Jason J , ElSherif May , Ye Lingyun , MacKinnon-Cameron Donna , Ambrose Ardith , Hatchette Todd F , Lang Amanda L S , Gillis Hayley D , Martin Irene , Demczuk Walter , Andrew Melissa K , Boivin Guy , Bowie William , Green Karen , Johnstone Jennie , Loeb Mark , McCarthy Anne , McGeer Allison , Semret Makeda , Trottier Sylvie , Valiquette Louis , Webster Duncan , McNeil Shelly
Published: October 2019

Background

In healthy adults aged ≥65 years, direct immunization with the 13-valent pneumococcal conjugate vaccine (PCV13) was shown effective at preventing vaccine-type pneumococcal community-acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD). Although PCV13 was licensed for use in Canadian adults aged >50 years, it was recommended for immunocompromised individuals who are at highest risk of IPD. In 2016, a recommendation was issued for use of PCV13 in immunocompetent adults aged ≥65 years, for the prevention of pCAP and IPD. This study aimed to compare pCAP cases attributed to PCV13 serotypes in adults aged 50–64 and ≥65 years.

Methods

Active surveillance for CAP and IPD was performed from 2010 to 2015 in adult hospitals across five Canadian provinces. To identify pCAP, blood culture, sputum culture, or a PCV13 serotype-specific urine antigen detection (ssUAD) were used. Serotype was assigned using Quellung reaction, PCR, or ssUAD. All pCAP cases were categorized by serotype and age groups. Patient demographics and outcome data were collected.

Results

Over years 2010–2015, 6687 CAP cases were tested. 835 pCAP cases were identified, of which 418 (50%) caused by a PCV13 serotype. The majority (74%) of PCV13-associated pCAP occurred in the adults aged ≥50 years, whereas only 41.4% (173/418) were in adults ≥65 years. PCV13 pCAP cases declined over the years, likely through herd immunity from childhood immunization. The yearly proportion of pCAP attributed to PCV13 serotypes for ages ≥50 remained high (67.5 to 80.6%), compared those occurring in the ≥65 age groups (35.1 to 49.4%). Compared with test-negative controls, pCAP cases in both age groups were more likely to be admitted to ICU, require mechanical ventilation, and had higher mortality. Of pCAP deaths, 61.4% and 82.3% were in the ≥65 and ≥50 age cohorts, respectively.

Conclusion

From year 2010 to 2015, adults hospitalized with PCV13 pCAP in the ≥65 age cohort accounted for less than half of the cases, whereas including the 50–64 age cohort increased the proportion to 74%. Similarly, the proportion of PCV13 pCAP deaths that occurred in adults aged ≥50 years was 82%, compared with 61% in the ≥65 age cohort. Expansion of PCV13 recommendations to include adults 50–64 years of age should be considered.

Disclosures

All authors: No reported disclosures.
2719. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Adults 18–55 Years of Age
Authors: Peterson James , Hedrick James , Pan Judy , Neveu David , Jordanov Emilia , Dhingra Mandeep S
Published: October 2019

Background

The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the immune lot consistency, and safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals 10–55 years of age.

Methods

A randomized, modified double-blind, multi-center study (NCT02842853) was conducted in the United States. The study evaluated 3344 meningococcal vaccine naïve adolescents and adults, who were randomly assigned to receive either a single dose of one of the three lots of MenACYW-TT conjugate vaccine or single dose of Menactra® [MenACWY-D]. Serum bactericidal assay with human complement (hSBA) and rabbit complement (rSBA) was used to measure antibodies against serogroups A, C, W, and Y at baseline before vaccination (Day 0) and 30 days post-vaccination. Safety data were collected up to 6 months post-vaccination. Herein we report the performance of MenACYW-TT in adults 18 through 55 years of age (n = 1,807).

Results

Immune equivalence was demonstrated across all 3 lots of MenACYW-TT conjugate vaccine based on geometric mean titers (GMTs) for all serogroups. Non-inferiority of immune responses, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated between MenACYW-TT and MenACWY-D for all four serogroups at Day 30 compared with baseline. The proportions of individuals (18–55 years) with hSBA ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-D administration for all four serogroups (A: 93.5% vs. 88.1%; C: 93.5% vs. 77.8%; W: 94.5% vs. 80.2%; Y: 98.6% vs. 81.2%). A similar trend was observed for post vaccination GMTs in adult participants. Reactogenicity profiles were comparable across study groups. Most unsolicited adverse events were of grade 1 or grade 2 intensity. No vaccine-related serious adverse events were reported.

Conclusion

MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with the licensed MenACWY-D vaccine when administered as a single dose to meningococcal vaccine naïve adults.

Disclosures

All authors: No reported disclosures.
2723. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Adolescents 10–17 Years of Age
Authors: Peterson James , Hedrick James , Pan Judy , Neveu David , Jordanov Emilia , Dhingra Mandeep S
Published: October 2019

Background

The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the immune lot consistency, and safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals 10–55 years of age.

Methods

A randomized, modified double-blind, multi-center study (NCT02842853) was conducted in the United States. The study evaluated 3344 meningococcal vaccine naïve adolescents and adults, who were randomly assigned to receive either a single dose of one of the three lots of MenACYW-TT conjugate vaccine or single dose of Menactra® [MenACWY-D]. Serum bactericidal assay with human complement (hSBA) and baby rabbit complement (rSBA) was used to measure antibodies against serogroups A, C, W and Y at baseline before vaccination (Day 0) and 30 days post-vaccination. Safety data were collected up to 6 months post-vaccination. Herein we report the performance of MenACYW-TT in adolescents 10 through 17 years of age (n = 1504).

Results

Immune equivalence was demonstrated across all 3 lots of MenACYW-TT conjugate vaccine based on geometric mean titers (GMTs) for all serogroups. Non-inferiority of immune responses, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated between MenACYW-TT and MenACWY-D for all four serogroups at Day 30 compared with baseline. The proportions of individuals (10–17 years) with hSBA ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-D administration for all four serogroups (A: 96.2% vs. 89.0%; C: 98.5% vs. 74.7%; W: 98.3% vs. 93.7%; Y: 99.1% vs. 94.3%). A similar trend was observed for post vaccination GMTs in adolescent participants. Reactogenicity profiles were comparable across study groups. Most unsolicited adverse events were of grade 1 or grade 2 intensity. No vaccine-related serious adverse events were reported.

Conclusion

MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with the licensed MenACWY-D vaccine when administered as a single dose to meningococcal vaccine naïve adolescents.

Disclosures

All authors: No reported disclosures.
2725. Immunogenicity and Safety of a Booster Dose of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Adolescents and Adults
Authors: Hedrick James , Simon Michael W , Christensen Shane , Anez German , Pan Judy , Jordanov Emilia , Dhingra Mandeep S
Published: October 2019

Background

The MenACYW-TT conjugate vaccine is a quadrivalent meningococcal vaccine that contains tetanus toxoid as carrier protein. Vaccine is intended for global use in all age groups (i.e., individuals 6 weeks of age and older). This Phase III study evaluated the safety and immunogenicity of the vaccine when compared with a licensed quadrivalent meningococcal conjugate vaccine in individuals ≥ 15 years of age.

Methods

A randomized, modified double-blind study (NCT02752906) was conducted in the United States and Puerto Rico. The study evaluated 810 participants primed with a licensed quadrivalent meningococcal conjugate vaccine (Menactra® [MenACWY-D] or MENVEO® [MenACWY-CRM]) in the 4 to 10 years prior to enrollment. Participants were randomly assigned to receive either a single booster dose of MenACYW-TT conjugate vaccine or MenACWY-D. Safety data were collected up to 6 months post-vaccination.

Results

Non-inferiority of immune response was demonstrated for MenACYW-TT vs. MenACWY-D based on percentages of participants achieving an serum bactericidal assay with human complement (hSBA) seroresponse for serogroups A, C, W, and Y at Day 30 post-vaccination. Post-vaccination hSBA geometric mean titers (GMTs) were higher following administration of MenACYW-TT compared with MenACWY-D for age subgroups ≥15 to < 18 years and ≥18 years. Relative to MenACWY-D, post-vaccination hSBA GMTs were higher for all 4 serogroups following administration of MenACYW-TT in participants who received the priming vaccine < 7 years prior to the booster; for participants who received priming vaccine ≥7 years prior to booster, post-vaccination GMTs were higher for serogroups C, W and Y, and comparable for serogroup A. In MenACWY-CRM-primed subjects, hSBA vaccine seroresponse rates were comparable for all 4 serogroups regardless of the booster vaccine administered. In MenACWY-D-primed subjects, hSBA seroresponse rates following MenACYW-TT booster administration were comparable for serogroups A and Y, and higher for serogroups C and W. Reactogenicity profiles were comparable across study groups.

Conclusion

MenACYW-TT conjugate vaccine was immunogenic and well tolerated when administered as a booster dose to individuals ≥15 years of age.

Disclosures

All authors: No reported disclosures.
2731. Does Last Season’s Influenza Vaccination Affect Current Season’s Vaccine Effectiveness in Young Children?
Authors: Rao Suchitra , Lamb Molly , Moss Angela , Asturias Edwin J
Published: October 2019

Background

We evaluated influenza VE over two consecutive years vs. the current season against influenza illness during two H3N2-predominant seasons in children receiving care at emergency/urgent care (ED/UC) facilities in metropolitan Colorado.

Methods

We conducted a test-negative case–control analysis of 1478 children aged 6 months to 8 years enrolled at Children’s Hospital Colorado ED/UC with influenza like illness during the 2016–2017 and 2017–2018 influenza seasons. The primary outcome was PCR-confirmed influenza and vaccination status was confirmed using electronic medical record and parental interviews. Vaccination status was defined as completely vaccinated (all doses of influenza vaccine according to child’s age); partially or not vaccinated children were defined as unvaccinated. Multivariable logistic regression models adjusted for high-risk medical condition, age, race and insurance status were used to calculate odds ratios (OR) and 95% confidence intervals. Vaccine effectiveness was calculated as (1 − OR) × 100.

Results

Of the 1224 (82.8%) children enrolled in the study with known vaccination status for both seasons, 361 (29%) tested positive for influenza. Overall, VE against influenza was 49% (95% CI, 33–61%) after adjusting for other covariates in the model. VE did not differ significantly between those vaccinated in both seasons and those vaccinated in only the current season (VE 69%, 95% CI 41–115) (Table 1).

Conclusion

Our estimates of influenza VE for two predominantly H3N2-influenza seasons in Colorado are comparable to the CDC -VE for children 6 months to 8 years. VE against ED or UC-attended influenza illness in children did not vary significantly by prior seasons’ vaccination status.

Disclosures

All authors: No reported disclosures.
2737. Comparison of Antibody Responses to Vaccination with a Pure Hemagglutinin Influenza Vaccine (rHA) and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Adults 60 Years and Older
Authors: Sarker Moumita , Branche Angela , Peasley Michael , Topham David
Published: October 2019

Background

Influenza is associated with increased mortality and morbidity for older adults. High-dose egg grown trivalent inactivated influenza vaccine (Fluzone HD) is safe and provides superior immune responses in older adults compared with standard dose (SD). Recently, two new vaccines have been licensed in the United States: cell cultured inactivated vaccine FluCelVax and baculovirus-expressed pure hemagglutinin (HA) vaccine FluBlok. Data from one study demonstrated higher efficacy with FluBlok than SD Fluzone in older adults. There is no data however comparing HD Fluzone to FluBlok and FluCelVax has not been studied at all. The purpose of this study was to assess hemagglutinin inhibition (HAI) antibody responses to vaccination with three vaccines in adults ≥ 60 years.

Methods

Adults ≥ 60 years were randomly assigned to receive one of the three vaccines: Fluzone HD, FluBlok and FluCelVax (Figure 1). Active influenza-like illness (ILI) surveillance was conducted with bi-weekly telephone calls. Serum samples were collected prior to vaccination and at day 7, 14, 28 and 180 and antibody responses assessed by HAI titer to A/Singapore/INFIMH-16–0019(H3N2), A/Michigan/45/2015(H1N1) and B/Colorado/6/2017 (Victoria) viruses as well as a circulating H3N2 strain. The primary endpoint was a 4-fold rise in antibody titer at day 28.

Results

48 subjects were vaccinated in October 2018. Mean age was 69 and 65% were female. Two subjects reported ILI symptoms and one was positive for infection (H1N1). A majority of subjects demonstrated pre-existing antibody to all three viruses (Figure 2, Blue). Geometric mean titers (GMT) for antibody responses to the influenza A viruses were similar for FluBlok (FB) and HD Fluzone (FZ) but lower for FluCelVax(FCB) subjects (Figure 2, Orange). A higher percent of FlubBlok subjects demonstrated 4-fold rise in antibody responses to the Victoria influenza B virus (FB GMT 140 vs. FZ GMT 116, P = 0.26).

Conclusion

In this small study, antibody responses were similar or higher in older adults after vaccination with FluBlok compared with Fluzone HD with lower responses demonstrated with FluCelvax. Emerging concerns about HA egg adaptation during vaccine development compels further study to determine the appropriate vaccination strategy for this vulnerable population.

Disclosures

All authors: No reported disclosures.
2739. Comparison of Hemagglutination Antibody Inhibition (HAI) Titers Following Influenza Vaccination by Birth Cohort and Repeated Influenza Vaccination History
Authors: Sherman Amy C , Lai Lilin , Bower Mary B , Natrajan Muktha S , Huerta Christopher M , Xu Yongxian , Mulligan Mark , Rouphael Nadine , Rouphael Nadine
Published: October 2019

Background

The host immune response to influenza vaccination can be affected by prior imprinting to a specific influenza strain based on birth cohort and prior influenza vaccination history. Understanding the underlying immune mechanisms is essential to development of an improved seasonal vaccine and an effective universal influenza vaccine.

Methods

This is a prospective pilot study, with a total of 20 subjects in either the H3N2 cohort (N = 10, born 1968–1977) or the H1N1 cohort (N = 10, born 1948–1957). Each cohort was further stratified by subjects who have received the influenza vaccine < 2 or ≥ 3 of the past 5 years. The FDA-approved quadrivalent 2018–19 influenza vaccine (containing A(H1N1), an A/Michigan/45/2015-like virus; A(H3N2), an A/Singapore/INFIMH-16–0019/2016-like virus; B/Colorado/06/2017-like virus; and B/Phuket/3073/2013-like virus) was administered on Day 1. Demographic information included age, gender, ethnicity, and BMI. HAI titers for each component of the vaccine were obtained at baseline, 29 days post-vaccination, and 180 days post-vaccination. HAI fold-change and HAI geometric mean titers (GMT) were analyzed.

Results

There was no significant difference between H1N1 or H3N2 HAI fold-change in the H3N2 birth cohort (P = 0.7496) or in the H1N1 birth cohort (P = 0.8237), Figure A. Comparing HAI fold-change for the repeatedly vs. minimally vaccinated groups, there was a significant higher fold change in the minimally vaccinated group (H1N1 HAI (P = 0.002) and H3N2 HAI (P < 0.0001), Figure B). GMT was higher at baseline for the repeatedly vaccinated group (H1N1, 70; H3N2, 98; vs. H1N1, 30; H3N2, 21 for the minimally vaccinated group); however, the GMT for the minimally vaccinated group was higher at day 29 (H1N1, 172; H3N2, 184; vs. H1N1, 422; H3N2, 299 for the minimally vaccinated group; Figure C). HAI titers and analysis at day 180 post vaccination are in progress.

Conclusion

There was no evidence of an imprinting effect by birth cohort for HAI titer magnitudes, even when stratified by vaccination history. There was a significantly higher HAI fold change for individuals who had received minimal influenza vaccinations in the past 5 years at 29 days post-vaccination. Individuals who had repeated vaccinations in the last 5 years had higher HAI GMT at baseline.

Disclosures

Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant.
167. Deep Space Infections in Injection Drug Users (IDU)
Authors: Bacon Alfred Emmanuel , Claudine Jurkovitz , Horton Terry , Caplan Richard , Fawcett Mitchell , Dal Nogare Ryan , Saunders Jessica , McGraw Patty
Published: October 2019

Background

The opioid epidemic in the US has increased attention to infectious complications of injection drug use (IDU). The goal of our study was to ascertain the impact of these infections on the health of our community and institutional burden considering that our institution does not discharge patients with IDU for outpatient IV antibiotic treatments due to lack of safe environment and compliance concerns.

Methods

This retrospective study reviewed IDU-associated deep space infections in an 1100 -bed medical center from 2010 through 2014. Pathogens, site of infection, mortality rates and, length of stay (LOS), 3- month readmission (inpatient + observation), leaving against medical advice (AMA) rates for those alive at discharge, were evaluated. ICD-9/10 coding identified admissions related to opioid use and deep infections (endocarditis, diskitis/osteomyelitis, sepsis/bacteremia, empyema). Only the most severe infection was counted for each patient. Charts were reviewed to determine whether IDU was associated with the entree infections.

Results

A total of 505 patients met criteria for deep space infections associated with IDU over 5 years. Of those, 305 (60%) were male, 146 (29%) black, 335 (66%) white, 271 (54%) were on Medicaid, 246 (49%) had sepsis/bacteremia, 67 (13%) had endocarditis,143 (28%) discitis/osteomyelitis, 22 (4%) empyema and 27 (5%) other. Mean age was 46 ± 12 years. LOS varied by disease state. The overall median was 10 days, from 8 days for bacteremia/sepsis up to 27 for endocarditis. There were 43 (9%) hospital deaths; 30 (6%) patients left AMA and 209 (45%) patients were readmitted within 3 months.

Conclusion

Deep space infections in IDU patients result in long LOS, high mortality and high rates of readmissions and departures AMA. Improved algorithms for management that include psychosocial models and incorporate cost-effective and safe antibiotic administration need to be developed.

Disclosures

All authors: No reported disclosures.
2745. Efficacy and Effectiveness of High-Dose Influenza Vaccine for Older Adults by Circulating Strain and Antigenic Match: A Systematic Review and Meta-Analysis
Authors: Lee Jason K H , Lam Gary K L , Shin Thomas , Samson Sandrine I , Greenberg David P , Chit Ayman
Published: October 2019

Background

Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared with standard-dose influenza vaccines (SD-IIV3) in adults ≥65 years against influenza-associated outcomes across all influenza seasons, during seasons where A/H3N2 or A/H1N1 strains predominantly circulated, and where there was an antigenic match or mismatch of the vaccine and circulating strains.

Methods

A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65 years. Results from individual seasons were extracted from the identified studies, and surveillance data from each season were used to determine the dominant circulating strains and antigenic match. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3.

Results

11 studies were meta-analyzed after screening 1,018 studies, providing data on 9 consecutive influenza seasons and over 12 million individuals receiving HD-IIV3. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared with SD-IIV3 (rVE = 15.9%, 95% CI: 4.1–26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7–11.0%), as well as influenza (rVE = 16.1%, 95% CI: 7.4–24.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3–37.6%), pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3–19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0–20.8%). Some numerical differences were observed in the pooled rVE of outcomes in matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating (Table 1).

Conclusion

Evidence over 9 influenza seasons suggest that HD-IIV3 is consistently more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection irrespective of circulating strain and antigenic match. This study was funded by sanofi pasteur.

Disclosures

All authors: No reported disclosures.