bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.