bluuebunny/crossref_metadata_2025_split huggingface dataset:
97. Tetravalent Dengue Vaccine (TAK-003) Development Program: A Bird’s Eye View
Authors: Tricou Vianney , Biswal Shibadas , Liu Mengya , Patel Sanjay S , Zent Olaf , Rauscher Martina , Perez Gonzalo , Kandeil Walid , Folschweiller Nicolas 
Published: December 2021

Abstract

Background
Dengue fever is a mosquito-borne viral disease endemic in 128 countries. An unmet clinical need remains for an effective vaccine that can be used more broadly than the vaccine presently available. A clinical development program has evaluated the long-term safety, immunogenicity, and vaccine efficacy (VE) of TAK-003, a live attenuated tetravalent dengue vaccine with a DENV-2 backbone engineered to elicit immune responses to all 4 dengue serotypes.

Methods
18 clinical trials in 13 countries have involved 28,175 seropositive/seronegative participants aged from 1.5-60 years from endemic/non-endemic regions. In the ongoing pivotal phase III study, 4–16-year-old healthy children (N=20,099) were randomized 2:1 to receive two doses of TAK-003 or placebo, 3 months apart for an evaluation of VE and safety over a multi-year period stratified pre-vaccination dengue serostatus. Active surveillance throughout the trial detected symptomatic dengue. The trial will continue up to 4–4.5 years post 2nd dose, and for another 25 months after a booster dose. Data up to 3 years after the second vaccination are currently available.

Results
Safety and immunogenicity data from Phase I/II studies established the final formulation and dosing schedule. Overall VE in the pivotal phase III study was 80.2% [95% CI: 73.3–85.3] against virologically confirmed dengue (VCD) at 12 months post 2nd dose. At 18 months, VE was 66.2% (95% CI: 49.1–77.5) in dengue-naive and 76.1% (95% CI: 68.5–81.9) in dengue pre-exposed participants, with VE of 90.4% (95% CI: 82.6–94.7) and 85.9% (95% CI: 31.9–97.1) for prevention of hospitalized VCD and dengue hemorrhagic fever, respectively. Cumulative VE against VCD from first dose to 3 years post 2nd dose was 62.0% (95% CI: 56.6–66.7) and 83.6% (95% CI: 76.8–88.4) in prevention of hospitalized VCD. Some decline in VE was observed over time mainly driven by outpatient dengue. Two doses of TAK-003 3 months apart were well-tolerated with no important safety risks identified up to 3 years after completion of the vaccination schedule.

Conclusion
TAK-003 is immunogenic against all 4 dengue serotypes and continues to be efficacious, well-tolerated, and with no evidence of disease enhancement in seronegative population up to 3 years post-vaccination.

Disclosures
Vianney Tricou, D Phil, Takeda Pharmaceuticals International (Employee) Shibadas Biswal, MD, Takeda Vaccines, Inc (Employee) Sanjay S. Patel, PhD, Takeda Pharmaceuticals International AG (Employee) Olaf Zent, MD, Takeda Pharmaceuticals International AG (Employee) Martina Rauscher, PhD, Takeda Pharmaceuticals International AG (Employee) Gonzalo Perez, MD, Takeda group companies (Employee) Walid Kandeil, MD, Takeda Pharmaceuticals International AG (Employee) Nicolas Folschweiller, PhD, Takeda (Employee)
99. Immune Responses to Influenza Vaccines in Children and Young Adults
Authors: Williams Katherine V , Zhai Bo , Alcorn John F , Nowalk Mary Patricia , Flannery Brendan , Levine Min , Moehling Krissy , Zimmerman Richard K , Martin Judith M 
Published: December 2021

Abstract

Background
Immune responses to influenza vaccines (IV) are influenced by pre-existing antibodies to vaccine components. Immune responses to vaccines were evaluated following vaccination with quadrivalent egg-based live-attenuated influenza vaccine (LAIV4) and cell-culture inactivated influenza vaccine (ccIIV4).

Methods
Racially diverse (48.0% non-white), healthy, community-dwelling children and young adults aged 4-21 years (median, 18.3 years) were randomized 1:1 in blocks of 4 to receive intramuscular ccIIV4 (Flucelvax: n=100) or nasal LAIV4 (FluMist: n=98); baseline demographics were similar between groups. Blood was drawn at day 0 pre-vaccination and at day 28 (21-35 days) post vaccination. Hemagglutination inhibition (HI) assays against egg-grown A/H1N1, A/H3N2, both vaccine B/strains and cell-grown A/H3N2 antigens were conducted. Geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers were analyzed.

Results
Day 0 GMTs were similar for LAIV4 and ccIIV4. Day 28 GMTs were higher for ccIIV4 (p&lt; 0.05) and increased following vaccination for all 5 antigens (p&lt; 0.05) except B/Phuket following LAIV4. The GMFR range was 2.4 to 3.0 for ccIIV4 and 1.0 to 1.3 for LAIV4. In linear regression controlling for age and prior season vaccination for both vaccines, baseline titers inversely predicted GMFR. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar within vaccine type.
Figure 1.

Day 0 and Day 28 A(H1N1) titers for ccIIV4
Figure 2.

Day 0 and Day 28 A(H1N1) titers for LAIV4

Conclusion
The HI response to ccIIV4 was greater than LAIV4 in this study of mostly older children. Day 0 HI titers were 1) a significant determinant of GMFR; 2) the strongest predictors of day 28 GMFR; and 3) more highly correlated (negatively) with GMFR following ccIIV4 than LAIV4. For both IV, the GMFR for cell-grown and egg-grown A/H3N2 antigens did not differ within IV type. Future studies incorporating immunoglobulin and cellular immune responses may delineate differences between these IV types not observable through HI assays.

Disclosures
Mary Patricia Nowalk, PhD, Merck & Co., Inc. (Grant/Research Support) Richard K. Zimmerman, MA;MD;MPH;MS, Sanofi Pasteur (Research Grant or Support) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)
804. Infection Control and Clinical Support in Long-Term Care Homes During the COVID-19 Pandemic in North Toronto: A Quasi-Experimental Study
Authors: Magaz Maria M , O’Brien Jaclyn , Williams Victoria R , Chan Christina , Chan Adrienne , Salt Natasha , Leis Jerome A 
Published: December 2021

Abstract

Background
Wave one of the COVID-19 pandemic in Ontario, Canada, resulted in significant institutional outbreaks associated with high case fatality among older adults. Our hospital formally partnered with congregate care homes in north Toronto to support infection control and clinical management before wave two of the COVID-19 pandemic. Our aim was to evaluate the impact of this program on resident and healthcare worker (HCW) outcomes.

Methods
A multicentre quasi-experimental study was conducted comparing outcomes between wave one (March-June, 2020) and wave two (October-December, 2020) among 17 congregate care homes (4 long term care homes and 13 residential homes). During wave two, weekly meetings and 42 on-site visits were conducted along with on-site daily hospital presence for all COVID-19 outbreaks to support infection control and resident management. The primary outcomes included COVID-19-case fatality rate as well as overall resident fatality including COVID-19 and non-COVID-19 related causes. Secondary outcomes included healthcare worker COVID-19 infections, and infection control practices among homes with paired audits (n=6), including hand hygiene, use of personal protective equipment, environmental cleaning and physical distancing practices.

Results
Among 2203 residents during wave one and 2287 residents during wave two, there was reduction in COVID-19 case fatality rate (38.1% vs. 13.4%; p&lt; 0.01), overall COVID-19-related fatality (2.3% vs. 1.0%; p&lt; 0.01) and non COVID-19 related fatality (8.3% vs. 3.5%; p&lt; 0.01). Weekly staff testing and increased syndromic surveillance was implemented during wave two. Among 2590 staff, there were 2.6% vs.4.2% staff who tested positive for COVID-19 during wave one and two, respectively. Changes in infection control practice were observed in regard to directly observed hand hygiene (83.3% vs. 100%), use of personal protective equipment (16.7% vs. 83.3%), environmental cleaning (66.7% vs. 100%) and physical distancing (66.7% vs. 83.3%).

Conclusion
Integration of hospital with community congregate care homes was associated with improvements in resident outcomes during wave two of the pandemic. Further longitudinal support and evaluation is needed to ensure sustainability.

Disclosures
All Authors: No reported disclosures
805. Outbreak of Ralstonia pickettii Bacteremia Caused by Contaminated Hydromorphone in a Universitary Hospital in Bogota, Colombia
Authors: Forero Shirley Vanessa Correa , Blanco Ivonne Tatiana Ordoñez , Martinez-Vernaza Samuel , Valderrama-Beltrán Sandra Liliana , Cortes Gloria , Miranda Claudia Janneth Linares , Rubio Angela Patricia Gonzalez , Garcia Viviana Andrea Pinzon 
Published: December 2021

Abstract

Background
Ralstonia pickettii are aerobic non fermenter gram negative bacilli isolated in water and soil. It is related to nosocomial infection outbreaks and considered an opportunistic pathogen. There have been outbreaks reports due to contaminated water systems and sterile drug solutions which mainly occurs during manufacturing. We present the report of an outbreak of R. pickettii bacteremia secondary to a contamination of hydromorphone vials.

Methods
In February 2021 an outbreak of R. pickettii bacteremia was identified. All isolates were from blood cultures with slow growth, thus indicating the culturing of liquid inputs, intravenous administration solutions and commonly used drugs among patients including hydromorphone. Mass spectrometry (MALDI-TOF) was used for the identification and automated microdilution to determine sensitivity to antimicrobials of the isolates and clonality analysis of genetic relationships was carried out using the DICE coefficient, UPGMA algorithm

Results
During the outbreak, 19 patients with R. pickettii bacteremia were identified The global attack rate was 1,9%. 11/19 (58%) were women and 13/19 (68%) of the isolations were from inward patients and 6/19 (32%) were from intensive care unit. Factors that could contribute to the appearance of the outbreak were underlying pathology, 2 patients with a diagnosis of diabetes mellitus, 10 patients with a diagnosis of arterial hypertension, 5 patients with obesity, 6 patients with heart disease, additionally 7 patients with a diagnosis of SARS COV 2 and 6 patients with the use of corticosteroids. The global attack rate was 1,9% and mortality was 31.5% (6 patients). R. pickettii was identified from two batches of hydromorphone by MALDI-TOF and the clonality study concluded that the isolates analyzed, were clonal with a 100% similarity. The associated mortality rate was 5/29 (26.3%).

Conclusion
We confirmed an outbreak of R. pickettii due to the contamination of two hydromorphone badges in Colombia. It is crucial to acknowledge the importance of infection control and surveillance during the COVID-19 pandemic as well as maintaining adequate quality control of medication production in order to avoid presenting this kind of outbreaks.

Disclosures
Sandra Liliana. Valderrama-Beltrán, MD, MSc, Biotoscana (Speaker’s Bureau)MSD (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Pfiezer (Speaker’s Bureau)
807. Same-day Transmission Analysis of Nosocomial Transmission Using Nanopore Whole Genome Sequencing
Authors: Sater Mohamad , Schwab Remy , Herriott Ian , Farrell Tim , Huntley Miriam 
Published: December 2021

Abstract

Background
Healthcare associated infections (HAIs) are a major contributor to patient morbidity and mortality worldwide. HAIs are increasingly important due to the rise of multidrug resistant pathogens which can lead to deadly nosocomial outbreaks. Current methods for investigating transmissions are slow, costly, or have poor detection resolution. A rapid, cost-effective and high-resolution method to identify transmission events is imperative to guide infection control. Whole genome sequencing of infecting pathogens paired with a single nucleotide polymorphism (SNP) analysis can provide high-resolution clonality determination, yet these methods typically have long turnaround times. Here we examined the utility of the Oxford Nanopore Technologies (ONT) platform, a rapid sequencing technology, for whole genome sequencing based transmission analysis.

Methods
We developed a SNP calling pipeline customized for ONT data, which exhibit higher sequencing error rates and can therefore be challenging for transmission analysis. The pipeline leverages the latest basecalling tools as well as a suite of custom variant calling and filtering algorithms to achieve highest accuracy in clonality calls compared to Illumina-based sequencing. We also capitalize on ONT long reads by assembling outbreak-specific genomes in order to overcome the need for an external reference genome.

Results
We examined 20 bacterial isolates from 5 HAI investigations previously performed at Day Zero Diagnostics as part of epiXact®, our commercialized Illumina-based HAI sequencing and analysis service. Using the ONT data and pipeline, we achieved greater than 90% SNP-calling sensitivity and precision, allowing 100% accuracy of clonality classification compared to Illumina-based results across common HAI species. We demonstrate the validity and increased resolution of our SNP analysis pipeline using assembled genomes from each outbreak. We also demonstrate that this ONT-based workflow can produce isolate to transmission determination (i.e. including WGS and analysis) in less than 24 hours.
SNP calling performance

ONT-based SNP calling sensitivity and precision compared to Illumina-based pipeline

Conclusion
We demonstrate the utility of ONT for HAI investigation, establishing the potential to transform healthcare epidemiology with same-day high-resolution transmission determination.

Disclosures
Mohamad Sater, PhD, Day Zero Diagnostics (Employee, Shareholder) Remy Schwab, MSc, Day Zero Diagnostics (Employee, Shareholder) Ian Herriott, BS, Day Zero Diagnostics (Employee, Shareholder) Tim Farrell, MS, Day Zero Diagnostics, Inc. (Employee, Shareholder) Miriam Huntley, PhD, Day Zero Diagnostics (Employee, Shareholder)
808. Appropriate Use of Cephalotin Before and After Implementation of a Cardiac Surgery Antibiotic Prophylaxis Protocol in Guatemala
Authors: Maldonado Herberth G , Ramay Brooke M , Sandoval Lourdes A 
Published: December 2021

Abstract

Background
The appropriate use of Surgical Antibiotic Prophylaxis (SAP) contributes to reducing the prevalence of Surgical Site Infections (SSI). Inappropriate use increases the risk of SSIs, hospitalization costs and potentially contributes to the emergence of antimicrobial resistance. We aimed to compare the appropriate use before and after implementing a SAP protocol in our institution

Methods
We conducted a retrospective chart review in patients older than 18 undergoing elective cardiac surgery with cardiopulmonary bypass using cephalotin as SSI prophylaxis. We excluded patients who received other antimicrobials for prophylaxis, those undergoing non-elective surgery, and patients with delayed sternal closure. We identified SSIs according to the Centers for Disease Prevention and Control criteria. We evaluated if appropriate dosing (2g-3g) and timing ( &gt;60 min.) occurred before the surgical incision, if redosing was administered, and if prophylaxis was administered &gt; 48 hours. We evaluated before and after implementation of the protocol (August 2016-July 2017; October 2017-2018)

Results
The study included 262 and 285 patients before and after protocol implementation, respectively. Patient characteristics were similar between comparator groups (Table 1). We found that 1.1% of patients vs. 63% of patients had appropriate dosing before the surgical incision, before and after protocol implementation, respectively (p &lt; 0.05). There was no difference in appropriate redosing when the duration of surgery was greater than 4 hours and no difference in inappropriate prophylaxis administration &gt; 48 hours after protocol implementation. A total of 8 SSIs were identified in each group, with no statistical difference in the incidence, length of stay, or clinical outcome between comparator groups
Table 1. Patient Characteristics and Appropriate use of Cephalotin Before and After Implementation of a Cardiac Surgery Antibiotic Prophylaxis Protocol in Guatemala

Conclusion
Based on our findings, implementing a local guideline-protocol for SAP resulted in significant improvement of pre-surgical antimicrobial dosing. We observed continual unnecessary administration of antibiotic prophylaxis in the postoperative period that needs more proactive interventional pharmacy-guided strategies such as automatic stops or audits width feedback.

Disclosures
Lourdes A. Sandoval, Master of Science in Pharmacovigilance and Pharmacoepidemiology, Abbott (Employee)
810. Cardiac Pacemaker Implantation Surgery: Automated Prediction of Surgical Site Infection
Authors: de Souza Flávio Henrique Batista , Couto Bráulio R G M , da Conceição Felipe Leandro Andrade , da Silva Gabriel Henrique Silvestre , Dias Igor Gonçalves , Rigueira Rafael Vieira Magno , Pimenta Gustavo Maciel , Martins Maurilio B , Mendes Júlio César O , Januário Guilherme Brangioni , Oliveira Rayane Thamires , de Vasconcelos Laura Ferraz , de Araújo Laís L , Rodrigues Ana Clara Resende , E Silva Camila Morais Oliveira , De Souza Eduarda Viana , Melo Júlia Faria , Assunção De Sá Maria Cláudia , Silva Walquíria Magalhães , Figueiredo Gabriella Mourão Cerqueira , Colares Jamile Doffénond , Junqueira Ludmila Paula Guimarães , Reis Maiara Cristina , Nobre Mariana Ribeiro 
Published: December 2021

Abstract

Background
A research focused on surgical site infection (SSI) was performed in patients undergoing cardiac pacemaker implantation surgery. The main objective is to statistically evaluate such incidences and enable a study of the prediction power of SSI through pattern recognition algorithms, in this case the Multilayer Perceptron (MLP).

Methods
Data were collected from five hospitals in the city of Belo Horizonte (more than 3,000,000 inhabitants), between July 2016 and June 2018, on SSI by the Hospital Infection Control Committees (CCIH) of the hospitals involved in the search. All data used in the analysis during their routine SSI surveillance procedures were collected. So, three procedures were performed: a treatment of the collected database for use of intact samples; a statistical analysis on the profile of the hospitals collected and; an assessment of the predictive power of five types of MLP (Backpropagation Standard, Momentum, Resilient Propagation, Weight Decay, and Quick Propagation) for SSI prediction. MLPs were tested with 3, 5, 7, and 10 hidden layer neurons and a database split for the resampling process (65% and 75% for testing, 35% and 25% for validation). They were compared by measuring AUC (Area Under the Curve - from 0 to 1) presented for each of the configurations.

Results
From 1394, 572 records were: 21% of deaths and 2.4% patients had SSI; from the confirmed SSI cases, approximately 64.3% had sites classified as “clean”; length of hospital stay ranged from 0 to 175 days (from 1 to 70 days); the average age is 67 years. The prediction power of SSI, the experiments achieved from 0.409 to 0.722.

Conclusion
Despite the considerable loss rate of more than 65% of the database samples due to the presence of noise, it was possible to have a relevant sampling for the profile evaluation of Belo Horizonte hospitals. Moreover, for the predictive process, although some configurations reached 0.722. To optimize data collection and enable other hospitals to use the SSI prediction tool (available in www.nois.org.br ), two mobile application were developed: one for monitoring the patient in the hospital and the other for monitoring after hospital discharge.

Disclosures
All Authors: No reported disclosures
812. The Impact of Post-Operative Cephalexin on Surgical Site (SSI) Infections During a Cefazolin Shortage
Authors: Brown Sara , Brigg Turner R , Chan Dominic 
Published: December 2021

Abstract

Background
Drug shortages directly impact patient care. Rates of drug shortages have declined except for antimicrobials, where shortage rates remain similar each year.1 In November 2018, a national cefazolin shortage occurred driving health systems to implement a therapeutic interchange of cefazolin for cephalexin for post-operative antimicrobial prophylaxis. The objective of this study is to determine whether SSI-rates change when post-operative cephalexin is used in placed of cefazolin.

Methods
This was a retrospective, observational cohort study of patients receiving post-operative antimicrobial prophylaxis at a community-based health system in Oregon and Washington between May 2018 – August 2019. Participants were divided into 3 periods for SSI-rate trend analysis: pre-shortage (May 2018 – October 2018), shortage (November 2018 – February 2019), and post-shortage (March 2019 – August 2019). The primary outcome was SSI-rates between groups.

Results
There were 6,378 patients in total (5,840 cefazolin vs. 538 cephalexin). There were no significant differences in baseline characteristics of age, sex, body mass index (BMI), or hospital location. The rate of SSI between pre-shortage and post-shortage cefazolin groups was not statistically different (14 [0.5%] vs. 23 [0.8%]; p=0.16). The primary outcome of SSI in the shortage group who received cephalexin was not statistically different (37 [0.6%] vs. 0 [0%]; p=0.07).

Conclusion
National drug shortages significantly impact patient care, often leading to seeking evidence-poor alternative medications. These results suggest cephalexin may be an acceptable post-operative prophylaxis antimicrobial if cefazolin is unavailable.

Disclosures
All Authors: No reported disclosures