bluuebunny/crossref_metadata_2025 huggingface dataset:
2661. Sarcopenia Increases Risk of Post-Surgical Infections in Kidney Transplant Recipients
Authors: Villacorta Evelyn , Acosta Luis , Myint Thein , Leedy Nicole , Lia Castellanos Ana , Gedaly Roberto
Published: October 2019

Background

Sarcopenia (reduced skeletal muscle mass) has been associated with serious infection in liver transplant recipients. We analyzed the association of sarcopenia and early post-surgical infections in kidney transplant recipients.

Methods

Retrospective cohort study of 125 patients underwent kidney transplantation from 2010 to 2014 at University of Kentucky Medical Center. Sarcopenia was diagnosed by measuring the skeletal muscle mass on computed tomography imaging obtained during the pre-transplant evaluation using SliceOmatic 5.0 software at L3 level (≤ 52.4 cm2/m2 in males and ≤ 38.5 cm2/m2 in females). Early post-transplant infections were confirmed by positive culture from blood, urine, and/or peritoneal fluid within 30 days after kidney transplantation. A generalized linear model (GLM) was used to identify variables predictive of post- surgical infection and Risk Ratio (RR) was obtained, with a P-value of < 0.05. The statistical analysis was performed with STATA version 12.0 (College Station, Texas).

Results

Among 125 patients, 52 (41.6%) were identified with sarcopenia, 110 (88.0%) patients were white, 76 (60.8%) male, with a median age of 56 (range 20–72) at the time of transplant. Diabetes was reported in 50 (40.0%) patients, obesity in 64 (51.6%) patients and smoking in 43 (34.6%) patients. Six (4.8%) patients had graft failure. Infections were identified in 22 (17.6%) patients, more than one source of infection was reported in 4 (3.2%) cases. The most common infections were urinary tract infection in 13 (10.4%) patients and bacteremia in 5 (4.0%) patients. The median time to development of infection was 9 days (range 1–27). In the bivariate analysis, sarcopenia was associated with high risk of post-surgical infections (RR 2.45; 95% CI 1.10–5.44). In multivariable analysis, sarcopenia was a significant independent predictor of infection (RR 2.58; 95% CI 1.20–5.52). None associations were found with other variables; age over 40 years, male sex, smoking, obesity and diabetes.

Conclusion

Our study suggested that sarcopenia was associated with an increased risk of early post-surgical infection in kidney transplant recipients.

Disclosures

All authors: No reported disclosures.
2664. Impact of Multidrug-Resistant Bacterial Infections in Solid-Organ Transplantation: The Value of Electronic Health Records-Based Registries and Data Extraction Tools
Authors: Puing Alfredo G , Xie Donglu , Adams-Huet Beverley , Barros Nicolas , Yek Christina , Wallace Ashley , Liu Terrence , Haley Robert W , La Hoz Ricardo M
Published: October 2019

Background

Antimicrobial usage is the most important driver of antimicrobial resistance. Despite compelling reasons to use antimicrobials judiciously, it has been challenging to implement antimicrobial stewardship programs (ASP) in the solid-organ transplant (SOT) population. The objective of our study is to assess the impact of multidrug-resistant bacterial infections (MDRBI) on the 1-year post-transplant survival in SOT recipients.

Methods

In this retrospective cohort study, we included all patients with a first SOT from January 1, 2010–December 31, 2016 at our institution. Patients were followed for a year. Data extraction tools retrieved information from the electronic health record (EHR) and merged it with data from the Social Security Death Index (SSDI) and Standard Transplant Analysis and Research (STAR) files. Charts of subjects with positive cultures were manually reviewed and adjudicated using CDC/ECDC and CDC/NHSN criteria. The 1-year MDRBI cumulative incidence and survival were estimated using the Kaplan–Meier method and compared using the Log-rank test. A Cox proportional hazards model was used to identify predictors of 1-year mortality. Cytomegalovirus (CMV) Infection, renal replacement therapy (RRT), and post-transplant extra-corporeal membrane oxygenation (ECMO) were analyzed as a time-dependent covariate.

Results

1,112 SOT recipients met inclusion criteria. Patient characteristics are shown in Table 1. 105 patients had at least one MDRBI. The cumulative incidence of MDRBI was 9.7% (95% CI 14.6–5.9) (Figure 1). The most common MDR pathogens were Vancomycin-resistant Enterococci and E. coli (Figure 2A), and the most common sites of infection were urinary tract infection and pneumonia (Figure 2B). The 1-year post-SOT survival in patients with MDR infection was 75.3% (95% CI 82.8–65.2) (Figure 2C). In multivariable analysis, MDRBI (HR = 6.2 [3.5–10.9]) and post-SOT RRT (HR = 17.8 [10.3–30.6]) were associated with an increased risk of 1-year mortality (Table 2).

Conclusion

MDRBI significantly impacts the 1-year survival of SOT recipients. Our results highlight the need to strengthen ASP measures in SOT. Additionally, this study illustrates the versatility of EHR-based registries and data extraction tools in the field of transplantation.

Disclosures

All authors: No reported disclosures.
2668. Β Lactam and Other Antibiotic Allergies in Patients Undergoing Solid-Organ and Hematopoietic Cell Transplantation
Authors: Imlay Hannah , Krantz Elizabeth M , Stohs Erica J , Lan Kristine F , Kim H Nina , Rakita Robert M , Limaye Ajit P , Wald Anna , Pergam Steven A , Liu Catherine
Published: October 2019

Background

Patients with reported β-lactam antibiotic allergies (BLA) are more likely to receive broad-spectrum antibiotics and experience adverse outcomes. There are limited data on the burden of β-lactam and other antibiotic allergies among solid-organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients.

Methods

We reviewed records of first-time adult SOT or allogeneic HCT recipients from January 1, 2013 to December 31, 2017 to characterize allergy labels at the time of transplant. Days of hospitalization and inpatient antibiotic use for pre-specified antimicrobials were collected for the first 100 days post-transplant, and incidence rate ratios (IRR) comparing BLA to non-BLA group were calculated using negative binomial models adjusted for transplant type, age, and diagnosis of cystic fibrosis as appropriate. If the adjusted estimates were significantly different for SOT and HCT recipients, separate models were presented.

Results

Among 2153 SOT (65%) and HCT (35%) recipients, 634 (29%) reported any antibiotic allergy and 347 (16%) reported BLAs (Figure 1). Of 634 patients with allergy labels, the most common were penicillins (40%), sulfa (29%), and cephalosporins (17%); 31% reported allergies to ≥2 classes of antibiotics. The most commonly reported reaction to β-lactams was rash (42%), followed by unknown (18%) and hives (17%). In a multivariable model (Table 1), patients with reported BLAs had significantly higher use of vancomycin (IRR 1.35 [95% CI 1.13, 1.60], P < 0.001) and significantly lower use of ampicillin-sulbactam (IRR 0.13 [0.05, 0.39], P < 0.001) and piperacillin–tazobactam (IRR 0.39 [0.25, 0.62], P < 0.001) compared with those without BLAs. For some antibiotics, the effect of BLA varied by SOT/HCT (Table 2). No significant differences in Clostridioides difficile infection or inpatient days were noted.

Conclusion

Transplant recipients have a high burden of reported antibiotic allergies, in particular BLAs. A BLA label was significantly associated with altered antibiotic prescribing in the early post-transplant period. Pre-transplant allergy evaluation may be helpful in directing antibiotic use following transplant as part of a comprehensive antibiotic stewardship program.

Disclosures

All authors: No reported disclosures.
2675. Changing Epidemiology of Bloodstream Infection During Chemotherapy for Acute Leukemia: Impact of Prophylactic Fluoroquinolone Restriction and Carbapenem Saving Strategy
Authors: Yi Yunmi , Cho Sung-Yeon , Lee Dong-Gun , Choi Jae-Ki , Lee Hyo-Jin , Kim Si-Hyun , Park Sun Hee , Choi Su-Mi , Choi Jung-Hyun , Yoo Jin-Hong
Published: October 2019

Background

Fluoroquinolone prophylaxis has been widely used in high-risk neutropenic patients with hematological malignancies, which may reduce bloodstream infection (BSI) and mortality. However, concerns about antibiotic resistance also exist. The aim of this study was to assess the impact of new institutional strategy of restricting fluoroquinolone prophylaxis and saving carbapenem, applied since October 2016. Fluoroquinolone prophylaxis was adopted only in remission induction chemotherapy, and carbapenems were saved until other antibiotics prove no effectiveness

Methods

We retrospectively reviewed all consecutive intensive chemotherapy episodes for acute leukemia from April 2016 to March 2017 at the Catholic Hematology Hospital. In addition, antibiotics consumption was assessed by calculating defined daily doses (DDDs) per 100 bed-days.

Results

Among 420 admissions during the study period, 201 and 219 admissions were identified before (period 1) and after (period 2) the strategy modification. Baseline characteristics including types of leukemia, chemotherapy, severity and duration of neutropenia were not different between the two periods.Development of febrile neutropenia (83.6% vs. 84.0%, P = 0.487), BSI (46.3% vs. 52.5%, P = 0.291), and septic shock (4.0% vs. 6.4%, P = 0.268) were not significantly different. Polymicrobial BSI increased significantly (7.1% vs. 20.0%, p = 0.012) in period 2. Quinolone resistance (97.8% vs. 43.6%, P < 0.001) and extended-spectrum β-lactamase producers (50% vs. 29.1%, P = 0.032) among Enterobacteriaceae were significantly reduced. Carbapenem-resistant Enterobacteriaceae was not isolated in period 2. Vancomycin resistance among enterococci (66.7% vs. 15%, P = 0.006) decreased. Consumption of ciprofloxacin (37.2 vs. 13.8) and carbapenem (22.3 vs. 16.8) decreased, while piperacillin/tazobactam consumption increased (5.2 vs. 13.0). BSI-related death (1.0% vs. 0.9%) was not increased.

Conclusion

Fluoroquinolone prophylaxis restriction and carbapenem saving strategies resulted in significant reduction of resistant bacterial BSIs, without increase in febrile neutropenia, BSI, septic shock, and BSI-related death. Antibiotics stewardship program can be tried in neutropenic patients, which may improve the ultimate outcome.

Disclosures

All authors: No reported disclosures.
2693. Clinical Presentation of Toxoplasmosis and 30-Day Mortality in Transplant Recipients at Two Academic Medical Centers
Authors: Adekunle Ruth O , Sherman Amy , Spicer Jennifer O , Spicer Jennifer O , Messina Julia A , Steinbrink Julie M , Sexton Mary Elizabeth , Lyon G Marshall , Mehta Aneesh , Phadke Varun , Woodworth Michael H
Published: October 2019

Background

Toxoplasma gondii causes opportunistic infections in transplant recipients after primary, donor-derived, or reactivated infection. Diagnosis in solid-organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients may be delayed due to varied clinical presentations, which can mimic bacterial sepsis. These delays could contribute to significant associated mortality, with a reported rate exceeding 50% in disseminated disease. Further exploration of expanded donor screening, targeted recipient prophylaxis, and enhanced early detection may be warranted. We therefore examined patient characteristics, clinical presentation, time to toxoplasmosis diagnosis, and mortality in transplant recipients at two centers.

Methods

A retrospective chart review of SOT and HSCT recipients diagnosed with toxoplasmosis from 2002–2018 at Emory Healthcare and Duke University Hospital was performed, with cases identified via an electronic query of relevant ICD codes, positive serum or CSF toxoplasmosis PCRs, and pathologic diagnoses. Patient characteristics, including age, sex, race, time since transplantation, method of toxoplasmosis diagnosis, and symptoms, were abstracted. Primary outcomes included time from transplant to diagnosis and estimated 30- and 90-day all-cause mortality.

Results

16 patients were identified, with a median age of 56 years at diagnosis. 50% were male, and the majority were white (63%) and SOT recipients (56%; see table). Median time from transplant to diagnosis was 295 days, with PCR the most common diagnostic modality (63%). In 31% of cases, toxoplasmosis was diagnosed after patient death. The most common clinical presentations were encephalitis (69%), respiratory failure (63%), renal failure (50%), diarrhea (50%), and septic shock (50%). The estimated all-cause 30-day and 90-day mortality rates were 56% and 69%, respectively.

Conclusion

Toxoplasmosis has diverse presentations in transplant recipients, likely contributing to diagnostic delays and high mortality. Future study is needed to determine clinical scenarios and risk factors where donor and recipient serologic screening may beneficial.

Disclosures

All authors: No reported disclosures.
2708. Genetic Structure of Streptococcus pneumoniae Isolated from Invasive Disease in Korea, 2014–2016
Authors: Kim Ye Kyung , Rhie Kyuyol , Choi Yun Young , Lee Hoan J , Yun Ki Wook , Choi Eun Hwa
Published: October 2019

Background

The extended-valency pneumococcal conjugate vaccines (PCVs) were implemented into Korean national immunization program in 2014. This study investigated the change in genetic structures of Streptococcus pneumoniae causing invasive pneumococcal disease (IPD) in Korean children after 10- and 13-valent conjugate vaccine (PCV10 and PCV13, respectively) use.

Methods

Between January 2014 and December 2016, invasive isolates were collected from 23 hospitals throughout Korea. Cases of IPD were defined by isolating pneumococci from normally sterile sites. Each pneumococcal isolate was identified using standard microbiological techniques and serotyped by Quellung reaction. The multi-locus sequence typing (MLST) was analyzed for randomly selected isolates.

Results

A total of 91 pneumococcal isolates were analyzed. Common serotypes were 10A (18.7%), 12F (11.0%), 15A (9.9%), 19A (9.9%), 15B/C (7.7%), 23A (6.6%), 35B (5.5%), and 23B (4.4%). The isolates belonged to 38 sequence types (STs), including 4 newly discovered STs. Of the 4 clonal complexes (CCs), 3 clonal complexes were antibiotic-resistant international clones. CC166 (11.9%) were associated with non-vaccine serotypes (NVTs; 11A, 15B/C, 23A, and 13). Serotypes of CC320 (10.9%) comprised of serotype 19A and 19F. The main serotypes responsible for CC81 (10.9%) were serogroup 15. New serotype-ST combinations were observed, especially in serotype 13 and serogroup 15. Also, a possibility of capsular switch event was noted between serogroup 6 and serogroup 15A.).

Conclusion

The introduction of extended-valency PCVs has resulted in the change of the genetic structure of pneumococcal isolates in Korean children. This study demonstrates that selective pressure from PCV10/13 caused predominant serotypes to be NVTs and genetic changes such as capsular switch events.

Disclosures

All authors: No reported disclosures.
2720. Potential Public Health Impact of a Pentavalent vaccine targeting Neisseria meningitidis Serogroups A, B, C, W, and Y
Authors: Snedecor Sonya J , Sirvastava Amit K , Palmer Paul , Huang Liping
Published: October 2019

Background

In the United States, most invasive meningococcal disease (IMD) is caused by serogroup B, followed by C, W, and Y. ACIP recommends universal vaccination against MenACWY (Category A) and MenB based on individual clinical decision-making (Category B) (Figure 1). In 2017, MenACWY vaccine uptake among adolescents was 44.3% for ≥2 doses and MenB uptake was 14.5% for ≥1 dose of a multi-dose series. A pentavalent vaccine (MenABCWY or Penta) has the potential to simplify immunization schedules and improve uptake to achieve further reductions in IMD. Our objective was to estimate the potential public health impact of Penta.

Methods

Using CDC’s enhanced meningococcal disease surveillance data (2015–2017 average), a dynamic transmission model was constructed to estimate the reduction in IMD over 10 years resulting from various implementation strategies including Penta within the existing United States meningococcal vaccination platform. The model assumed that 2-doses of Penta could provide 95% and 85% direct and 25.5% and 0% indirect protection, respectively, against serogroups ACWY and B for 5 years, with 10% relative waning per year. For partial compliance (1 dose Penta only), we assumed protection against ACWY equal to 2-doses but partial protection against B. Future uptake of Penta was assumed higher than 2017 uptake, and sensitivity analyses with lower uptake were conducted.

Results

Based on 2015–2017 epidemiology, the current schedule and uptake of MenACWY and MenB vaccines (total 4 doses) was estimated to avert 149 IMD cases over 10 years. Replacing MenACWY and/or MenB doses with Penta at 11 and/or 16 years could avert more cases, ranging from 172 to 243 (Figure 2). The most beneficial schedule was 2-doses of Penta at 11 years and 1-dose Penta at 16 years. Additional sensitivity analyses indicated that, even assuming current uptake rates, more cases could be prevented by utilizing Penta.

Conclusion

Replacing one or more MenACWY/MenB vaccine doses with Penta could improve prevention of IMD caused by all 5 meningococcal serogroups among the US adolescent population and provide substantial public health benefit while reducing the recommended number of vaccine administrations.

Disclosures

All authors: No reported disclosures.
2748. Single Intranasal (IN) Dose of M2SR (M2-Deficient Single Replication) Live Influenza Vaccine Protects Adults Against Subsequent Challenge with a Substantially Drifted H3N2 Strain
Authors: Eiden Joseph , Volckaert Bram , Rudenko Oleg , Ellis Ruth , Aitchison Roger , Herber Renee , Belshe Robert , Greenberg Harry , Coelingh Kathleen , Kawaoka Yoshihiro , Neumann Gabriele , Bilsel Pamuk
Published: October 2019

Background

Demonstration of protection by a M2SR (M2 deficient Single Replication) monovalent H3N2 vaccine was assessed in a phase 2a clinical trial in which the challenge virus was substantially drifted from the vaccine. M2SR is an investigational, live virus vaccine containing hemagglutinin (HA) and neuraminidase (NA) selected from targeted Type A influenza strains. M2SR undergoes only a single round of infection in the respiratory epithelium but evokes an immune response profile similar to wild-type influenza virus and protects ferrets against both homologous and heterologous influenza variants.

Methods

A blinded, randomized, placebo-controlled human challenge study (EudraCT #: 2017-004971-30) was conducted with M2SR containing HA and NA from A/Brisbane/10/2007 (H3N2). 18–55-year-old subjects received 1 IN dose of saline or 108 TCID50 of vaccine. 4 weeks later, 99 subjects were challenged IN with 106 TCID50 H3N2 A/Belgium/4217/2015 (Figures 1 and 2).

Results

Adverse events (AE) were similar between placebo (N = 51) and M2SR recipients (N = 48) during the 28 days after immunization. After challenge with A/Belgium/4217/2015, 35% of M2SR recipients experienced influenza infection and illness, compared with 49% of placebo subjects (Figure 3). An 18% reduction in viral load was noted after challenge for M2SR subjects. Serum microneutralization response to vaccine was detected in 54% of M2SR subjects (vs. 0/51 placebo subjects), and among these subjects a 34% reduction in viral load and 51% reduction in symptom scores was noted after challenge vs placebo. Among the 29% of subjects with post-vaccine response to both vaccine and challenge strains, a 62% reduction in viral load and 56% reduction in symptom scores was noted after challenge with highly drifted H3N2 (Figure 4).

Conclusion

One dose of M2SR protected healthy adults against influenza infection and illness with a highly drifted challenge strain. This is believed to be the first study to demonstrate protection against challenge with an influenza strain substantially different from the vaccine and indicates potential for improved breadth of protection by M2SR compared with current vaccines. The mild vaccine AE profile supports clinical trials of additional dose levels and regimens to enhance drifted strain protection by M2SR.

Disclosures

All authors: No reported disclosures.
2751. Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED): Methods
Authors: Burgess Timothy , Richard Stephanie , Collins Limone , Colombo Rhonda , Ganesan Anuradha , Geaney Casey , Lalani Tahaniyat , Markelz Ana E , Maves Ryan , Mende Katrin , Schofield Christina , Seshadri Srihari , Spooner Christina , Utz Gregory , Warkentien Tyler , Coles Christian L
Published: October 2019

Background

Most influenza vaccines come from inactivated virus grown in egg culture, and studies suggest that egg-adapted virus may have decreased immunogenicity in humans for certain influenza A strains. Cell culture-based and recombinant vaccines may be more immunogenic, but comparative studies are lacking. We are conducting a randomized, controlled trial of 3 FDA-licensed influenza vaccines (cell culture, recombinant, and egg culture) to assess differences in immunogenicity and effectiveness in adults.

Methods

A total of 10,650 eligible adults will be individually randomized 1:1:1 (cell culture, recombinant, or egg-based vaccine) over 2 influenza seasons (2018–2019 and 2019–2020) at military facilities in geographically diverse locations in the US Participants who are not military recruits will report the presence or absence of ILI symptoms on a weekly basis through an automated electronic (text message or email) survey; those who experience ILI symptoms will be scheduled for two in-person visits. Military recruits who experience an ILI report will report directly to clinic and will not receive weekly surveillance reminders (Figure 1).

Results

Enrollment for year 1 of PAIVED occurred November 7 to December 31, 2018 at 5 military bases. During this season, 1,623 participants were enrolled, among whom 34% were randomized to receive cell culture vaccine, 33% to recombinant vaccine, and 33% to egg-based vaccine. The participants were 61% active military, 19% retired military, and 20% military dependents. One quarter of the participants were women, and the participants were 18–88 years old, median 26 years of age. Among the 1,559 participants with complete data, 324 (21%) experienced ILI at least once. Blood and swab samples were successfully collected at visit 1 from 93% of the participants with case-defined ILIs.

Conclusion

The initial phase of PAIVED successfully enrolled and randomized 1,623 participants during the 2018/2019 influenza season. Follow-up of this season’s participants is on-going. PAIVED will apply lessons learned during the 2018/2019 influenza season to the next season’s study implementation, with the goal of enrolling more than 9,000 additional participants through increasing the number of individuals enrolled at some sites and adding new sites to the trial.

Disclosures

All authors: No reported disclosures.
2754. Phase 1 Trial of an mRNA-Based Combination Vaccine Against hMPV and PIV3
Authors: Shaw Christine , Lee Heather , Knightly Conor , Kalidindi Shiva , Zaks Tal , Smolenov Igor , Panther Lori
Published: October 2019

Background

Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are important causes of upper and lower respiratory tract infections, particularly in young children. Despite their public health impact, no effective therapeutic or preventive options are available. mRNA-1653 is a mRNA-based investigational combination vaccine against hMPV and PIV3, and consists of two distinct mRNA sequences encoding the fusion proteins of hMPV and PIV3, co-formulated in lipid nanoparticles.

Methods

This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study assesses the safety and immunogenicity of mRNA-1653 in healthy adults aged 18–49. The 124-subject study evaluates four vaccine dose levels (25, 75, 150, and 300 µg) administered intramuscularly in either single-dose or two-dose (Day 1, Month 1) vaccination schedules, with follow-up through 1 year after the last vaccination. Objectives include safety and immunogenicity measured by hMPV- and PIV3-specific neutralizing antibody titers.

Results

An interim analysis demonstrated that the mRNA-1653 vaccine was generally well-tolerated at all dose levels. Neutralizing antibodies against hMPV and PIV3 were present at baseline in all subjects, consistent with prior exposure to both viruses. A single dose of mRNA-1653 boosted serum neutralization titers against both hMPV and PIV3, and the magnitude of boosting was similar at all dose levels. The geometric mean ratio of Month 1 to baseline titers was approximately 6 for hMPV and 3 for PIV3. A second dose of mRNA-1653 at Month 1 was not associated with further increase of hMPV or PIV3 neutralization titers.

Conclusion

mRNA-1653 is well-tolerated and induces a functional immune response, and is therefore a promising vaccine candidate for the prevention of pediatric respiratory tract diseases caused by hMPV and PIV3.

Disclosures

All authors: No reported disclosures.
2762. A Cohort Analysis of Completion of the Pediatric Measles-Mumps-Rubella-Varicella Series in the United States
Authors: Wolfson Lara J , Nyaku Mawuli K , Surati Shikha , Liu Zhiwen , Pawaskar Manjiri D
Published: October 2019

Background

Since 2006, the recommended US vaccination schedule has included combination Measles-Mumps-Rubella (MMR) vaccine and separate Varicella (V) vaccine administered as first dose between 12–15 months, and second dose between 4–6 years, administered either separately or as a combination MMRV vaccine. Vaccine coverage alone does not provide information on the timeliness of vaccine receipt, a critical step in ensuring optimal protection, thus, we sought to evaluate overall series completion rates and identify factors related to under-vaccination.

Methods

A cohort of children born between 2006 and 2010, with continuous enrollment from birth to age 7 in the MarketScan® Commercial Claims and Encounters Database was studied. The administration of first and second doses of MMR- and V-containing vaccines was evaluated. Administration timeliness was categorized as recommended, acceptably early (prior to age 4 for the second dose), late (after the recommended time period), invalid, or missing at least one vaccine. A logistic regression analysis evaluated factors associated with under-vaccination.

Results

Among the 104,999 children included, 55.9% were vaccinated within the recommended time periods for both first and second doses, with timeliness higher for the second dose (80.1%) than the first dose (63.5%). By age 4, 20.1% of children were missing the first dose of either MMR or V (or both) and by age 7, 26.6% of children were missing at least one dose, with 9.4% missing all required vaccines. Factors associated with missed or delayed vaccination included geographic region, vaccination by a provider other than a pediatrician, and, for the second dose, having missed or delayed the first dose. Having additional children in the family was associated with a higher likelihood of missed or delayed vaccination for the first dose, but with a lower likelihood of missed or delayed vaccination for the second dose.

Conclusion

About one in four children were missing at least one dose of MMR or V by age 7, indicating vaccine coverage is below Healthy People 2020 95% target. Additionally, delays in administration of the first dose indicate a potential for the development of cohorts of susceptible children large enough to sustain outbreaks. Strategies for addressing timeliness of vaccine receipt should incorporate factors associated with under-vaccination.

Disclosures

All authors: No reported disclosures.
169. Multidrug-Resistant Bacteria Are Common Cause of Neutropenic Fever and Increase Mortality Among Patients with Hematologic Malignancies in Uganda
Authors: Lubwama Margaret , Adams Scott , Muwonge Catherine , Bwanga Freddie , Kateete David , Nabiryo Barbara , Kagwa Paul , Namubiru Betty , Orem Jackson , Phipps Warren
Published: October 2019

Background

Cancer patients are at risk of developing severe infections. Empiric management of infections is complicated by emerging antimicrobial resistance and changing local epidemiology of organisms. We sought to determine predominant species causing bacteremia, their antimicrobial resistance profiles, and their contribution to mortality among hematologic cancer patients with febrile neutropenia at the Uganda Cancer Institute.

Methods

Blood drawn from participants during a febrile neutropenic episode (FNE; fever ≥37.5°C and neutrophil count ≤1,000 cells/µL) was cultured in the BACTEC 9120 blood culture system. Bacteria from positive cultures were identified biochemically. Antimicrobial susceptibility testing was performed with the disc diffusion method. Logistic regression and proportional hazards regression were applied to estimate associations between participant characteristics and FNE, bacteremia, and mortality.

Results

Of 246 participants, 74 (30%) had an FNE. During the first FNE, 6/21 (29%) participants with acute lymphocytic leukemia (ALL) developed bacteremia compared with 16/31 (52%) with acute myeloid leukemia (AML) (OR 2.22 (0.65, 7.4)). AML patients were specifically at higher risk of Gram-negative bacteremia (OR 4.59 (1.09, 19.3). Of the 41 aerobic bacteria isolated, 32 (78%) were Gram-negative, the most common being Klebsiella pneumoniae (11; 34%). Seventeen (53%) of the Gram-negative bacteria displayed the extended spectrum β lactamase phenotype and 5 (16%) were resistant to carbapenems. One of the eight Enterococcus species was vancomycin resistant. Overall survival among patients with FNE was 54% at 30 days and 19% at 100 days. Bacteremia was associated with higher mortality within 30 days (HR 2.1 (0.99, 4.45)) and 100 days (31% vs.10%; HR 2.23 (1.09, 4.59)).

Conclusion

Multidrug-resistant bacteria are the main cause of bacteremia and increase mortality in febrile neutropenic hematologic cancer patients at the UCI. Enhanced microbial surveillance, infection control and antimicrobial stewardship programs are needed to guide therapy and address emerging antimicrobial resistance at our institution.

Disclosures

All authors: No reported disclosures.
2764. Generation of a Balanced, Tetravalent Dengue Vaccine Based on Contemporary Strains Using a Computational, Synthetic Biology-Based Platform
Authors: Wang Ying , Stauft Charles B , Raviprakash Kanakatte , Coleman J Robert , Mueller Steffen
Published: October 2019

Background

The WHO estimates that there may be 50 million cases of dengue virus (DENV) infection worldwide every year. There is no safe vaccine against DENV licensed in the United States. The development of a balanced and effective anti-DENV vaccine is vital to preventing morbidity and mortality. Codagenix used its proprietary SAVE (Synthetic Attenuated Virus Engineering) platform to generate and test a live attenuated, tetravalent vaccine against DENV.

Methods

Codagenix used SAVE to substitute under-represented human codons and codon-pairs into the E protein sequences of contemporary strains of DENV1-4, producing either a fully human-cell-deoptimized prM-E (E-Min), or a partially deoptimized prM-E (E-W/Min) to allow for balancing of the vaccine’s immunogenicity. Full genomes containing deoptimized E-Min and E-W/Min in the DENV2 backbone were transfected into cells to recover live-attenuated, human-cell-deoptimized vaccine strains. Mice were vaccinated with 106 FFU of each DENV vaccine (alone or together), boosted on day 21 and assessed for neutralizing antibodies by PRNT50 and survival after lethal challenge with mouse-adapted wild-type (WT) DENV. Cynomolgus macaques were immunized with a mixture of 106 FFU of each DENV vaccine strain. Two doses were administered on study day 1 and 57 and serum neutralizing antibodies were determined on day 57 and 85 by a microneutralization assay.

Results

SAVE deoptimized DENV viruses grew to wild-type (between 107 and 108 FFU/ml) levels at permissive temperatures (<37C). All vaccine strains generated neutralizing antibody levels comparable to WT. A tetravalent formulation containing all four E-Min strains protected mice from lethal challenge with DENV3. A tetravalent formulation of Codagenix DENV-E-W/Min vaccine elicited a robust and balanced neutralizing antibody response in non-human primates (NHPs) against all four DENV serotypes after a single dose. A second vaccine dose did not boost antibody titers significantly.

Conclusion

The ability to rationally balance the attenuation of multiple vaccine strains, thereby avoiding antibody-dependent enhancement, is a unique advantage of the Codagenix SAVE platform. Codagenix DENV vaccine viruses generated balanced, sterilizing immunity in NHPs after one dose.

Disclosures

All authors: No reported disclosures.
2772. HCMV gB Ectodomain Subunit and gB mRNA Vaccines Reduce AD-3 Immunodominance and Elicit More Durable Antibody Responses Than gB/MF59 Immunization
Authors: Nelson Cody S , Jenks Jennifer A , Pardi Norbert , Roark Hunter K , Goodwin Matthew , Weissman Drew , Permar Sallie R
Published: October 2019

Background

A vaccine to prevent maternal acquisition of human cytomegalovirus (HCMV) during pregnancy is one potential strategy to reduce the incidence of congenital disease. The MF59-adjuvanted glycoprotein B (gB/MF59) protein subunit vaccine is the most efficacious tested to-date, though achieved only 50% efficacy in phase 2 trial. We previously identified that gB/MF59 vaccination elicited poor heterologous virus neutralization and an immunodominant response against non-neutralizing/cytosolic antigenic domain 3 (AD-3) (Figure 1). Thus, we sought novel gB vaccination strategies to improve functional antibody responses and reduce AD-3 immunodominance.

Methods

Groups of juvenile New Zealand White rabbits (n = 6) were administered 3 sequential doses of gB protein with an MF59-like squalene adjuvant IM, gB ectodomain protein (lacking AD-3) + squalene adjuvant IM, or lipid nanoparticle (LNP)-packaged nucleoside-modified mRNA encoding gB ID.

Results

The AD-3 immunodominant IgG response seen in human vaccinees was closely mimicked in rabbits, with 78% of binding antibodies directed against this region in the gB protein group compared with 1% and 46% in the ectodomain and mRNA-LNP-vaccinated groups respectively (Figure 2). All vaccines were highly immunogenic with similar kinetics and comparable peak gB-binding/functional antibody responses. However, both ectodomain and mRNA-LNP-immunized rabbits exhibited enhanced durability of IgG binding to gB protein (P = 0.04 and 0.02, respectively), and the mRNA-LNP group had more durable binding of cell membrane-associated gB (P < 0.001) (Figure 3). Additionally, ectodomain and mRNA-LNP-vaccinated rabbits had increased durability of antibodies targeting neutralizing epitopes AD-4 and AD-5 (P < 0.01). Finally, low-magnitude gB-specific T-cell activity was observed in the gB protein and mRNA-LNP groups, though not in ectodomain-vaccinated rabbits.

Conclusion

Altogether these data suggest that gB ectodomain subunit and gB mRNA-LNP vaccine formulations reduced targeting of non-neutralizing epitope AD-3 and elicited more durable IgG responses than gB protein vaccination. These next-generation HCMV vaccine candidates aiming to improve upon the partial efficacy of gB/MF59 vaccination should be further evaluated in preclinical models.

Disclosures

All authors: No reported disclosures.
2774. Impact of Yellow Fever Vaccine and Recombinant Zoster Vaccine Shortages on Patients Presenting to a Travel Clinic
Authors: Baca Alec , Gundacker Nathan , Sanchez Joyce L
Published: October 2019

Background

In 2017, the United States experienced a national shortage of the yellow fever vaccine (YF-Vax). In response to this, the US Food and Drug Administration (FDA) approved the use of Stamaril in a limited number of clinics across the country. This was soon followed by a shortage of the recently approved recombinant zoster vaccine (RZV) in 2018. This project describes the impact of both vaccine shortages on patients presenting to the Travel Health Clinic at Froedtert and the Medical College of Wisconsin.

Methods

A retrospective review of Travel Health Clinic medical records between January and December of 2018 was performed. Information regarding patient demographics, travel destination, vaccination rates, reasons for not vaccinating, and referral information was obtained.

Results

Of the 306 patients seen in 2018, 98 were traveling to countries with active yellow fever transmission. Due to the YF-Vax shortage, 59.2% of these patients were referred to another clinic for Stamaril and 7.1% were unable to get the vaccine before departure. The remaining patients qualified for a medical exemption, had an itinerary that was lower risk for yellow fever, or their subsequent vaccine history was unknown. Additional cost for Stamaril at referral locations ranged from $169.50-$315.00 per person with a travel distance of 15–272 miles to the referred clinic. Regarding RZV, 134 clinic patients were qualified to receive the vaccine. 57.5% did not receive RZV due to vaccine shortage, 15.7% were referred to another clinic for RZV, while 15.7% were able to receive the vaccine during their appointment. Of these patients, 31.3% were covered under Medicare, thus necessitating referral to a pharmacy for vaccine coverage.

Conclusion

We encountered high rates of unvaccinated travelers who would have qualified for and benefitted from YF-Vax and RZV in 2018. Even among those who could receive the recommended vaccines, there was substantial additional cost and inconvenience. This illustrates the considerable negative impact of the YF-Vax and RZV vaccine shortages. Further efforts are necessary to make these vaccines more accessible to the community.

Disclosures

All authors: No reported disclosures.
2777. Live-Attenuated Vaccine Against RSV Generates Robust Cellular and Humoral Immune Responses
Authors: Mueller Steffen , Nouen Cyril Le , Buchholz Ursula J , Kalkeri Raj , Koide Fusataka , Collins Peter , Coleman J Robert
Published: October 2019

Background

In people over 65, there are on average 177,000 hospitalizations and 14,000 deaths because of respiratory syncytial virus (RSV) each year. Elderly patients infected with RSV can suffer serious infections leading to pneumonia and congestive heart failure. RSV vaccines have failed in the elderly in part because they have been unable to mount a robust cellular immune response.

Methods

RSV-MinL4.0 is a live-attenuated intranasal vaccine candidate that was generated by codon pair deoptimization of the L gene followed by the addition of four stabilizing mutations found via stress passaging. Four African Green Monkeys (AGMs) per group were vaccinated with RSV-MinL4.0 or wild-type (WT) RSV at 2 × 106 PFU, boosted on day 28 and challenged with wild-type (WT) RSV on day 104. Oropharyngeal swabs and tracheal lavage were collected daily and every other day, respectively, to evaluate virus shedding (qPCR) and blood was drawn on days 1, 14, 21, 28, and 49 for antibody titers (PRNT50), and PBMC activation (IFNγ ELISPOT with whole inactivated virus).

Results

MinL4.0 was 2 to 3 log10 attenuated when compared with WT RSV in AGMs. Despite the presence of antibodies on day 28, there was a “take” of the boost indicating the potential for this vaccine to be immunogenic in the elderly with pre-existing circulating antibodies (Figure 1A). MinL4.0 led to robust activation of PBMCs comparable to WT RSV (> 2,000 spots per 106 total cells, Figure 1B). Shedding of the vaccine and challenge viruses was minimal (data not shown).

Conclusion

MinL4.0 led to robust activation of cellular and humoral immune responses, which are critical for induction of protective immunity in the elderly. Animals were protected from WT challenge. Preliminary data in AGMs with pre-existing antibodies to RSV indicate that circulating antibodies do not prevent vaccine “take,” critical for a vaccine targeting sero-positive elderly individuals.

Disclosures

All authors: No reported disclosures.
2782. Host Immune Response to Enterovirus and Parechovirus Systemic Infections in Children
Authors: Sasidharan Anjana , Hassan Ferdaus , Selvarangan Rangaraj
Published: October 2019

Background

Enterovirus (EV) and human Parechovirus (PeV) cause a range of illness including asymptomatic to systemic infections. The host immune response in children, especially the one induced by PeV, is largely unknown. The aim of this study was to determine the immune response induced by EV and PeV in cerebrospinal fluid (CSF) and plasma obtained from children with systemic infection.

Methods

Left-over CSF and paired blood samples collected from children with laboratory confirmed EV and PeV central nervous system-infection were enrolled in this study. EV/PeV-negative CSF and paired plasma from children was used as controls. Level of cytokines and chemokines were measured using a customized 21-plex ELISA panel that included 16 cytokines and 5 chemokines (Millipore, CA). Additionally, clinical characteristics of all the patients were collected to determine the potential association between the immune response and pathogenicity.

Results

Total of 74 samples were enrolled and divided into 3 groups, EV (n = 27), PeV (n = 23) and control group (n = 24). Median age of all the three groups was 2 weeks (IQR 2–4 weeks).The key analytes which had a significant difference between each groups are show in the Table. In general, EV induced more robust cytokine secretion than PeV and control group. Anti-viral response such as IFN-g was remarkably absent in both CSF and plasma in PeV group compared with EV group (P < 0.05). Only IL-8 was significantly higher (P < 0.05) in EV CSF group compared with any other groups or sample types. Level of all the chemokines measured were much higher in all the three groups but significant difference was found between PeV CSF and plasma for IP-10 and MCP-1 chemokines (P < 0.05).

Conclusion

In this study, we demonstrate that EV and PeV induces distinct immune response in children with systemic infections. While EV induces more robust inflammation, PeV-induced inflammation appears to be either weak or absent in CSF, but robust in plasma. The suppressed pro-inflammatory response might facilitate PeV growth and proliferation in CSF and might play a role in disease severity. Further studies are needed to fully understand the differential immune response induced by these two viruses.

Disclosures

All authors: No reported disclosures.
2786. The Role of Respiratory Panel PCR in Decreasing Antibiotic Exposure in Patients Diagnosed With a Respiratory Viral Infection
Authors: Vostal Alexander , Gonzalez Michael Antonio , Darling Nellie , Papastamelos Christine , Natarajan Madhuri , Kumar Princy , Timpone Joseph
Published: October 2019

Background

Respiratory viral infections (RVI) are becoming increasingly recognized as an important cause of pneumonia. There is limited data regarding the role of rapid PCR testing for RVI and its effect on antibiotic duration and length of stay (LOS).

Methods

We performed a single-center, retrospective chart review in adult patients who were admitted and underwent evaluation with the FilmArray Multiplex Respiratory Panel (RP) (Biomerieux™) using a random sample from July 1, 2016 through April 1, 2018. Patient clinical and virologic characteristics, LOS, antibiotic use, and duration of treatment were collected. A Student’s t-test was performed for all comparisons.

Results

We identified 540 patients who were admitted and underwent RP testing. The mean age was 57.1 years (range 19–99), 50.2% were immunocompromised, 23.8% were transplant recipients, 70.4% had respiratory symptoms, and 35.7% had an admitting diagnosis of pneumonia. 55.6% required supplemental O2 and 24.6% had an ICU admission that required either noninvasive or mechanical ventilation. 22.6% (N = 122) of these patients were diagnosed with an RVI, of which 15 were co-infected with two or more respiratory viruses. There were 41 (34%) rhinovirus/enterovirus, 41 (34%) influenza (Types A/H1, A/H3, A/H1-2209, and B), 16 (13%) RSV, 15 (12%) coronavirus (Types NL63, OC43, 229E, and HKU1), 13 (11%) metapneumovirus, and 7 (5%) parainfluenza (Types 2, 3, and 4). 85.2% (104/122) of patients with an RVI received antibiotics. The mean LOS and antibiotic duration were 9.07 days and 7.31 days for patients with an RVI when compared with 11.5 days and 10.4 days for patients without an RVI (P = 0.098; P = 0.032), respectively. In patients with an RVI and negative bacterial cultures, the mean LOS was 8.4 days and mean antibiotic duration was 5.9 days when compared with 16.4 days and 15.5 days for all patients with positive bacterial cultures (P = 0.003; P < 0.0001), respectively. The mean time from available results of + RP to antibiotic discontinuation was 5.1 days in the setting of negative bacterial cultures.

Conclusion

Although antibiotic exposure and time to discontinuation still remained significant in patients diagnosed with an RVI, there was a marked reduction in LOS and antibiotic duration in the subset of patients with an RVI and negative bacterial cultures.

Disclosures

All authors: No reported disclosures.
172. Risk Factors for 30-Day Mortality in Patients with Staphylococcus aureus Bacteremia at a Community Hospital: A Prospective Case–Control Study
Authors: Hoffmann Charles , Watkins Gordon , DeSimone Patrick , Hallisey Peter , Hutchinson David , Colodny Stephen , Burket Jeffrey , Michael Amanda , Klein Jo-anne , Welc Christina
Published: October 2019

Background

Staphylococcus aureus bacteremia (SAB) is associated with 30-day all-cause mortality rates approaching 20–30%. The purpose of this case–control study was to evaluate risk factors for 30-day mortality in patients with SAB at a community hospital.

Methods

As part of an antimicrobial stewardship program (ASP) initiative mandating Infectious Diseases consultation for episodes of SAB, our ASP prospectively monitored all cases of SAB at a 341-bed community hospital in Jefferson Hills, PA from April 2017–February 2019. Cases included patients with 30-day mortality from the initial positive blood culture. Only the first episode of SAB was included; patients were excluded if a treatment plan was not established (e.g., left against medical advice). Patient demographics, comorbidities, laboratory results, and clinical management of SAB were evaluated. Inferential statistics were used to analyze risk factors associated with 30-day mortality.

Results

100 patients with SAB were included; 18 (18%) experienced 30-day mortality. Cases were older (median age 76.5 vs. 64 years, P < 0.001), more likely to be located in the intensive care unit (ICU) at time of ASP review (55.6% vs. 30.5%, P = 0.043), and less likely to have initial blood cultures obtained in the emergency department (ED) (38.9% vs. 80.5%, P < 0.001). Variables associated with significantly higher odds for 30-day mortality in univariate analysis: older age, location in ICU at time of ASP review, initial blood cultures obtained at a location other than the ED, and total Charlson Comorbidity Index (CCI). Variables with P < 0.2 on univariate analysis were analyzed via multivariate logistic regression (Table 1).

Conclusion

Results show that bacteremia due to MRSA and total CCI were not significantly associated with 30-day mortality in SAB, whereas older age was identified as a risk factor. Patients with initial blood cultures obtained at a location other than the ED were at increased odds for 30-day mortality on univariate analysis, which may raise concern for delayed diagnosis.

Disclosures

All authors: No reported disclosures.