bluuebunny/crossref_metadata_2025 huggingface dataset:
83. ID Coaches Contribute to a Highly Effective Learning Experience for Third-Year Medical Students Rotating on the Infectious Diseases Consult Service
Authors: Roberts Erin , Sigler Rachel , Welford Elliott , Keehner Jocelyn , Wooten Darcy
Published: December 2021

Background

Education on infections in hospitalized patients, antimicrobial selection, and principles of antimicrobial stewardship are foundational to all clinicians. Incorporating early learners into Infectious Diseases (ID) consult services has the potential to build a strong fund of knowledge in these content domains, but also poses potential challenges. We evaluated the impact of a novel clinical rotation and supporting curriculum on third-year medical students rotating on the ID consult service for 2 weeks during their 12-week Internal Medicine clerkship at the University of California, San Diego.

Methods

Third-year medical students who selected to rotate on the ID consult service were given an hour-long orientation about the service and common infectious syndromes. They were provided with a checklist of clinical skills to complete during the rotation. In addition to daily rounds and clinical care, ID Coaches (ID faculty and senior ID fellows) met with students weekly for 1-2 hours to review ID topics, practice oral presentations, and/or conduct physical exam finding rounds. We surveyed medical students to assess the effectiveness of the rotation.

Results

Forty third-year medical students participated in the 2-week ID consult rotation between June 2020-May 2021; 31 (77%) completed the rotation evaluation. Seventy percent or more of students reported that the ID rotation facilitated their learning across 8 of 10 ID-content domains (Figure 1). More students reported that the ID Coach facilitated learning (71%) compared to the clinical skills checklist (42%). Students highlighted learning about antimicrobial selection, stewardship, and clinical reasoning on the rotation but reported that teaching was limited when the service census was high (Figure 2).

Figure 1: Percent of Students Rating the ID Consult Rotation as Extremely or Very Effective in Facilitating Learning Across 10 Domains

Figure 2: Students' Reflections on the Effectiveness of the ID Consult Rotation

Conclusion

Third-year medical students found that a 2-week rotation on the ID consult service was highly effective in teaching foundational ID content and general medicine skills. Incorporating early learners into a busy and complex subspecialty consult service can be facilitated through the use of supplemental curricular tools such as ID Coaches.

Disclosures

Darcy Wooten, MD, MS, Nothing to disclose
84. Paying for Parenthood: Misinterpretation of ABIM Leave Policies May Lead to Unnecessary Extension of ID Fellowships
Authors: Stead Wendy , Gardiner Catherine P , Desrochers Laura P , Finn Kathleen , McDonald Furman S , Melfe Michael , Melia Michael
Published: December 2021

Background

Many trainees plan pregnancy during fellowship training. A study of internal medicine program directors (PDs) demonstrated frequent misinterpretation of American Board of Internal Medicine (ABIM) leave policies when applied to parental leave. The ABIM has since attempted to clarify its leave and deficits in training policies. The primary aim of this study was to investigate how infectious disease (ID) program directors interpret the current ABIM leave policies in crafting parental leave for trainees.

Methods

We surveyed 155 ID program directors in an online, anonymous questionnaire regarding their knowledge of ABIM leave policies and application toward trainees’ leaves of absence.

Results

75/155 (48%) of program directors responded to the survey. Most respondents incorrectly identified the leave limits permitted by ABIM policies, and a majority mistakenly chose to extend training when a clinically competent fellow was within their allowed duration of leave.(Figure 1) Most respondents correctly identified that equal time is permitted for both birth and non-birth parent parental leave, however, reported leave durations did not reflect this equity. PDs reported the majority (60.4%) of ID trainee maternity/birth parent leaves at their programs were ≤7weeks and 4.6% were≤3 weeks, while only 7% were≥12 weeks. In contrast, 50% of paternity/non birth parent leaves were ≤3weeks and none were ≥12 weeks. (Figure 2) PDs utilize various strategies to prevent extending training for fellows taking parental leaves that exceed the limits allowed by ABIM policies, including creating “home electives,” though 34% counsel trainees to take “a shorter maternity leave.”

Conclusion

Fellowship program directors often misinterpret ABIM leave policies, and misapply them when given example scenarios. These findings have clear implications for trainees’ family planning and may lead to shortened parental leaves and inappropriate fellowship training extensions.

Disclosures

All Authors: No reported disclosures
85. A Virtual Platform for Mentoring Clinician Educators at IDWeek is as Effective as In-Person
Authors: Riedel David J , Luther Vera , Luther Vera , Armstrong Wendy , Armstrong Wendy , Bonura Erin , Melia Michael , Schwartz Brian
Published: December 2021

Background

Career mentorship for clinician educators (CE) may be difficult to obtain within one’s home institution. During IDWeek 2018 and 2019, a mentoring program pairing junior faculty pursuing careers as CEs with more experienced CEs from other institutions was found to be feasible and effective. During IDWeek 2020, the program was transitioned to a virtual format. We assessed the feasibility and efficacy of this virtual mentoring program.

Methods

Junior and established CEs were recruited through the IDSA listserv and Medical Education Community of Practice and paired. Mentees completed an individual development plan (IDP) and identified discussion topics for their meeting. Mentors received training on successful mentoring and their mentee’s IDP and CV prior to meeting. Mentor and mentees met via videoconference for one hour during IDWeek 2020, created an action plan, and scheduled a follow-up call. Post-participation surveys were sent to mentees and mentors.

Results

30 mentor and mentee pairs were matched; 1 pair did not meet. Compared to IDWeek 2018 (17) and 2019 (20), the 2020 program had more mentees (30). 24 (80%) mentees completed the pre-session survey; 17 (59%) mentees and 20 (69%) mentors completed the post-session survey. When compared to survey results from mentees in 2018-19 who met in-person, mentees in the virtual format reported similarly high rates of satisfaction, planned to make changes at work, had an increase in confidence, and felt it was a valuable experience (Table 1). Mentors also reported high rates of satisfaction with the experience in 2020 and were likely to participate in the program next year (Table 2). Only 1 (6%) mentee reported that the virtual format negatively impacted their experience, although 6 (30%) mentors reported some negative impact of the virtual format (Table 3).

Table 1. Post-session mentee survey responses across 2 in-person years (2018, 2019) compared to the virtual mentoring program (2020)

Table 2. Post-session mentor survey responses across 2 in-person years (2018, 2019) compared to the virtual mentoring program (2020)

Table 3. Experience of mentees and mentors with the 2020 virtual mentoring program

Conclusion

A virtual mentoring program for CEs was feasible and as effective for mentees as an in-person format. Some mentors felt that the virtual nature did negatively impact the experience although it had minimal negative impact on mentees.

Disclosures

David J. Riedel, MD, MPH , Gilead (Advisor or Review Panel member)ViiV (Advisor or Review Panel member) Vera Luther, MD, Nothing to disclose Wendy Armstrong, MD, Nothing to disclose Brian Schwartz, MD, Nothing to disclose
86. Making the APPropriate Choice: Utilization of a Smartphone Application to Optimize Antimicrobial Decisions Among Internal Medicine Trainees
Authors: Brooke Thomas , Pfaeffle Herman , Guillory Walter , raiciulescu Sorana , Ressner Roseanne
Published: December 2021

Background

Use of an application (App) to shape antimicrobial stewardship (AS) practice is largely unknown. Walter Reed National Military Medical Center (WRNNMC) is a tertiary military academic medical center where 2020 AS guidelines transitioned to a mobile App platform. This project aimed to determine barriers to AS and the impact of an App combined with educational sessions (ES) on Internal Medicine (IM) trainee prescribing practices for common Infectious Diseases (ID) syndromes.

Methods

After an orientation, participants completed a pre-intervention survey. Once weekly ES reinforcing App content was implemented over 12 weeks after which a post-intervention survey was completed. Each weekly session covered a specific ID syndrome. Survey data was analyzed using SPSS Version 27 with paired t-test.

Results

Amongst 81 IM trainees, 59 (73%) completed both pre- and post-intervention surveys, of whom 39% were PGY1, 31% PGY2, and 27% PGY3. Common AS barriers included lack of knowledge, deference to seniority, established habits, and time needed to make an informed decision. The App and ES improved performance of an antimicrobial timeout (78%), IV to PO switch (61%), therapy de-escalation (56%), and antibiogram knowledge (68%) with 90% of trainees reporting increased access. Weekly ES led to 75% reporting it had at least a moderate impact on learning. Across all ID syndromes, each PGY year reported increased confidence in management post-intervention (P< 0.001) but PGY1s in particular saw the largest gain in confidence with antibiogram, febrile neutropenia, and hospital/ventilator acquired pneumonia categories. Usage of the App increased from 42% to 90% after the intervention, and 95% modified their prescribing practice based on the App. The most common barrier to App usage was forgetting to use the App.

Conclusion

Utilization of an App combined with ES improved multiple domains of AS practice among IM trainees leading to a modification in antimicrobial prescribing practice in the vast majority of participants. PGY1 trainees in particular may see a large benefit which supports implementation of AS training early in the academic year. This model can be used to build a sustainable AS trainee curriculum augmenting the learning and management of common ID syndromes.

Disclosures

All Authors: No reported disclosures
87. Infectious Disease Diversity, Equity, and Antiracism (ID2EA): A Dedicated Curriculum for Infectious Disease Professionals
Authors: Gleeson Shana , Bathgate Meghan , Frederick Jennifer , Desruisseaux Mahalia S , Meyer Jaimie , Virata Michael D , Zapata Heidi , Shenoi Sheela , Radin Joanna , Golden Marjorie , Trubin Paul , Shaw Albert , Friedland Gerald , Aoun-Barakat Lydia A
Published: December 2021

Background

Systemic bias in the health care system has adverse effects on health outcomes. Educational programs examining the relationship between structural racism and health inequities are needed to translate knowledge into equitable care. The Yale School of Medicine Infectious Disease (ID) Section designed and piloted an innovative Infectious Disease Diversity, Equity, and Anti-Racism (ID2EA) curriculum to better understand and confront these issues.

Methods

The ID Section collaborated with pedagogical experts to create a curriculum. A baseline survey of ID faculty and trainees was used to gauge relevant knowledge, attitudes, skills, and topics of interest to participants. The curriculum was designed as a “roadmap” of interactive sessions (“roadmap stops”) focused on topics identified by respondents. Evaluations were performed after events to guide curriculum development and monitor its acceptance and effectiveness.

Results

All respondents (n=28) to the baseline survey agreed that discussion of race and ethnicity should be integrated into medical training. Most respondents (96%) had experience or knowledge of racial microaggressions in the workplace. Fewer (75%) felt comfortable talking to patients about race and only 68% felt confident teaching learners how to decrease bias in care. The survey identified topics of highest priority to participants, including building trust with patients (75%), providing racially sensitive care (68%) and establishing dialogue with community members (57%). Roadmap stops were constructed based on these priorities, with sessions on race-based medical experimentation and inequities, racial segregation and its impact on health, medical mistrust, and a skill building session on improving patient-centered communication. On follow-up surveys (n=18-28), most participants (93%) saw the sessions as a valuable way to spend time and the majority (91%) reported an impact on their understanding of racism in healthcare; specific changes in thinking were qualitatively coded.

Conclusion

Our findings demonstrate the positive impact of a curriculum to help understand racism and inequities in medicine. Building and implementing a diversity, inclusion, and anti-racism curriculum in ID sections is feasible, beneficial, and valued.

Disclosures

Jaimie Meyer, MD, Gilead Sciences (Scientific Research Study Investigator) Sheela Shenoi, MD, MPH, Merck (Other Financial or Material Support, SS’s spouse worked for Merck pharmaceuticals 1997-2007 and retains company stock in his retirement account. There is no conflict of interest, but it is included in the interest of full disclosure.) Marjorie Golden, MD, Iterum Pharmaceuticals (Consultant)
89. Positive Blood Culture Trends and Variability among U.S. Hospitals, 2012-2017
Authors: McCarthy Natalie , Hatfield Kelly M , Baggs James , Kazakova Sophia , Wolford Hannah , Olubajo Babatunde , Jernigan John A , Jernigan John A , Reddy Sujan
Published: December 2021

Background

Although studies have shown blood culture rates have remained stable in recent years, understanding the variability in positivity over time and among hospitals may inform diagnostic and antimicrobial stewardship efforts.

Methods

We included all discharges from hospitals participating in the Premier Healthcare Database and Cerner Health Facts from 2012-2017 in months where a hospital reported at least one blood culture with antimicrobial susceptibility results. A blood culture episode was defined as one or more cultures drawn within 1 hour. Episodes on or before day 3 were defined as admission episodes (AE), and those drawn on day 4 or later were defined as post-admission episodes (PAE). Culture episodes yielding any organism were categorized as pathogen+ (i.e., at least 1 non-commensal organism identified) or commensal (i.e., only commensal organisms identified). Positive or commensal episode rates were calculated as the percentage of pathogen+ or commensal episodes among all blood culture episodes for AE and PAE. Logistic regression with generalized estimating equation models accounting for hospital-level clustering were used to measure time trends and facility level associations.

Results

Among 19.6 million discharges in 493 hospitals, 7.5 million blood culture episodes were identified; 336,102 (4.5%) were pathogen+, and 110,236 (1.5%) were commensals. The rate of pathogen+ AEs increased from 4.2% to 4.7% over the study period (p< .0001) and there was no significant temporal trend in the rate of pathogen+ PAEs (p=.7956) (Figure 1). AE commensals decreased significantly in 2016-2017 compared to previous years (1.6% in 2012 to 1.3% in 2017; p=.0092), and PAE commensals decreased significantly over the study period from 2.0% to 1.2% (p< .0001) (Figure 1). We observed substantial inter-hospital variability for each outcome (Figure 2). In addition, differences among hospital characteristics and seasonality were noted for AE and PAE pathogen+ rates and AE commensal rates (Figure 3), but not urbanicity or teaching hospital status.

Monthly Positivity Rate of Blood Culture Episodes, Premier Healthcare Database and Cerner Health Facts, 2012-2017

Adjusted Odds Ratios and 95% Confidence Intervals of Blood Culture Episode Positive (Non-Commensal) and Commensal Rates and Associated Characteristics

Conclusion

While an increase AE pathogen+ rates and decrease in commensal rates could indicate improved culture ordering and collection practices, significant seasonal, regional, and facility-level variability calls for further investigation.

Disclosures

John A. Jernigan, MD, MS, Nothing to disclose
91. Gaps and Opportunities in Antimicrobial Stewardship Programs in Asia: A Survey of 10 Countries
Authors: Chang Feng-Yee , Chuang Yin-Ching , Veeraraghavan Balaji , Apisarnthanarak Anucha , Tayzon Maria Fe R , Kwa Lay Hoon Andrea , Chiu Cheng-Hsun , Deris Zakuan Zainy , Husin Suraya Amir , Hashim Hazimah , Karuniawati Anis , Ahmed Altaf , Matsumoto Tetsuya , Nguyen Van Kinh , Huong Dinh Thi Thu
Published: December 2021

Background

Most studies on hospital antimicrobial stewardship (AMS) status and practices are conducted in the west, and there is a lack of such data from Asian countries. The objective of this survey was to determine existing AMS practices and gaps, and challenges in implementing AMS programs in secondary and tertiary acute-care hospitals in 10 Asian countries.

Methods

A 70-item questionnaire was disseminated to hospitals fulfilling inclusion criteria and responses were collected from 10 April 2020 to 9 April 2021. The survey, specific to the Asian hospital setting, enquired about hospital leadership support for AMS; AMS team membership and training; AMS interventions; AMS monitoring and reporting; hospital infrastructure; and education. These were subdivided into core and supplementary components, adapted from the Transatlantic Taskforce on Antimicrobial Resistance set of core and supplementary indicators for hospital AMS programs, and the US Centers for Disease Control and Prevention checklist for core elements of hospital AMS programs.

Results

A total of 349 hospitals from Cambodia, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Taiwan, Thailand and Vietnam responded. Overall, only 47 hospitals fulfilled all 12 core components, and there were inter-country differences in terms of performance. The hospitals generally did well in terms of the AMS team (ie, comprising at least a physician leader responsible for AMS activities, a pharmacist, and infection control and microbiology personnel), and access to a timely and reliable microbiology service, with mean positive response rates (PRR) of ≥ 80% for these indicators (Figure 1). In the core components of AMS program interventions, and AMS monitoring and reporting, the lower mean PRR ( > 60%) revealed that Asia has wider gaps in these areas versus gold standards. Although many hospitals had formal hospital leadership statements to support AMS (mean PPR 85.6%), this was not always matched by allocated financial support for AMS activities (mean PPR 57.1%).

Figure 1

Conclusion

For all core components of an AMS program, most Asian hospitals participating in this survey fell short of international gold standards. Inter-country differences in gaps highlight that country-specific solutions are needed to improve current standards in AMS.

Disclosures

Tetsuya Matsumoto, MD; PhD, MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)
94. Infectious Complications of Left Ventricular Assist Devices
Authors: Harris Courtney , Coakley Lara , Mehra Mandeep R , Mallidi Hari R , Baden Lindsey R , Woolley Ann E
Published: December 2021

Background

Left ventricular assist devices (VAD) have significantly increased survival for patients with advanced heart failure. While advancements in devices during the past 10 years have improved thrombotic and bleeding complications, infection remains a significant cause of morbidity and mortality. We assessed the incidence and risk factors of VAD infections at our institution.

Methods

A single center, retrospective study of patients who had VAD implanted between January 2007 and December 2020 was performed. Patients with concurrent right sided mechanical circulatory support devices were excluded. Patient demographics, clinical characteristics, labs, microbiology data, and antimicrobials were obtained from the electronic medical records. Clinical outcomes were adjudicated by 2 independent physicians. VAD infections were classified using the ISHLT 2011 guidelines.

Results

241 patients had durable VAD implanted in this 14-year period, with a median time of 3 years follow-up. 134 (56%) patients had a clinically significant infection; 42 (31.3%) were VAD specific infections, 42 (31.3%) were VAD related, and 50 (37.4%) were non-VAD related. 95% of VAD specific infections were driveline site infections. 98% of patients with VAD related infections had a concurrent blood stream infection. Of the 50 non-VAD infections, 72% involved either a lower respiratory, urinary tract, or Clostridium difficile infection. Median time from VAD implantation to infection was 5 months. 44 (32.8%) had their first infection during the index hospitalization, of which 27 (61.4%) were non-VAD infections. 78 (58.2%) had one infection, compared with 38 (28.4%) who had two or more infections. 17 (12.7%) had recurrence of their initial infection and 6 (35%) occurred despite being on suppressive antibiotics. 48 of 134 (36%) infected patients were transplanted. 57 of 134 (42.5%) died compared to 33 of 107 (31%) without an infection.

Conclusion

More than half of VAD patients at our center during a 14-year time period had an infectious complication and higher mortality rate compared to those without an infectious complication. Further studies are needed to assess the immunologic risk factors for the increased risk of non-device associated infections in VAD patients.

Disclosures

Mandeep R. Mehra, MD, Abbott (Consultant)Baim Institute for Clinical Research (Consultant)FineHeart (Consultant)NupulseCV (Consultant) Ann E. Woolley, MD, MPH, COVAX (Consultant)
95. Impact of Penetrating Trauma on Surgical Site Infection Standardized Infection Ratio (SIR) for Colon Procedures
Authors: Boston Kelley M , Ellsworth Misti , Thomas Jocelyn , McInnis-Cole Tawanna A , Ostrosky-Zeichner Luis
Published: December 2021

Background

Colon surgery (COLO) is one of the focus areas for the the Centers for Medicare and Medicaid Services (CMS) Hospital Inpatient Quality Reporting (IQR) Program. Standardized criteria from the National Healthcare Surveillance Network (NSHN) are used to define surgical site infections (SSI) and to assess and weight standardized risk variables, so that all organizations can be judged to the same standard. Performance is compared though use of a standardized infection ratio (SIR), which is the observed number of infections, divided by the “predicted” number of infections, given the number and type of surgeries performed.

Methods

A retrospective review of medical records and NHSN documentation was conducted for 778 COLO procedures that were performed at a large academic and level 1 trauma center between January 2019 and December 2020. Initial review of the data showed that the increases in SIR were primarily concentrated in trauma patients with intestinal injury and fecal spillage. SIR for adult procedures were calculated using the NHSN Complex 30-Day SSI Data for IQR Report model, which the metric used by the CMS IQR. The CDC NHSN Statistics Calculator was used to compare SIR for procedures coded as trauma and non-trauma. As a proxy for patients with penetrating trauma, SIR for patients coded as trauma who had a surgical wound class noted as dirty was compared to SIR for patients coded as trauma with surgical wound class coded as contaminated or clean-contaminated.

Results

For the CMS model, there was a statistically significant difference (p = 0.0003) between SIR for trauma (SIR = 3.451) and non-trauma (SIR = 1.071) procedures. There was also a statistically significant difference (p=0.0014) between trauma procedures with dirty surgical wound class (SIR = 6.608), compared to those with wounds categorized as contaminated or clean-contaminated (SIR = 2.235).

NHSN Adult Complex 30 Days SIR comparison for COLO SSI with and without trauma

NHSN Adult Complex 30 Days SIR comparison for trauma COLO procedures with dirty wound class description, against COLO procedures with wound class described as clean or clean-contaminated

Conclusion

Risk factors currently included in the model for COLO SSI may not adequately account for the increased risk from penetrating trauma with fecal spillage. Trauma and wound class should be added to the CMS IQR risk model for SIR.

Disclosures

Kelley M. Boston, MPH, CIC, CPHQ, FAPIC, Infection Prevention & Management Associates (Employee, Shareholder) Luis Ostrosky-Zeichner, MD, Amplyx (Consultant)Cidara (Consultant)F2G (Consultant)Gilead (Grant/Research Support, Speaker's Bureau)Pfizer (Scientific Research Study Investigator, Speaker's Bureau)Scynexis (Grant/Research Support, Scientific Research Study Investigator)Viracor (Consultant)
96. Relative Vaccine Effectiveness Against Influenza-Related and Any Respiratory-Related Hospital Encounter During the 2019/20 High Influenza Activity Period: A Comprehensive Real-World Analysis to Compare Quadrivalent Cell-based and Egg-based Influenza Vaccines
Authors: Divino Victoria , Postma Maarten , Pelton Stephen I , Mould-Quevedo Joaquin F , Anupindi Ruthwik , DeKoven Mitchell , levin myron J
Published: December 2021

Background

Changes in the influenza hemagglutinin protein during replication of influenza in eggs during vaccine production may contribute to low vaccine effectiveness (VE). This phenomenon, egg adaptation, can explain VE differences between egg-based (QIVe-SD) and cell-based (QIVc) quadrivalent influenza vaccines. This research evaluated the relative vaccine effectiveness (rVE) of QIVc versus QIVe-SD in the reduction of influenza-related and any respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season.

Methods

A retrospective cohort analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the U.S. (IQVIA PharMetrics® Plus). The adjusted number of events and rates of influenza-related hospitalizations/ER visits and respiratory-related hospitalizations/ER visits were assessed using inverse probability of treatment weighting (IPTW). Poisson regression was used to estimate relative vaccine effectiveness (rVE). In the main analysis, the study period was from Aug 4, 2019 to Mar 7, 2020 (ending early to avoid any influenza outcome misclassification with COVD-19 infection). In the assessment of the high influenza activity period (HIAP), the analysis period was restricted to Dec 8, 2019 to Mar 7, 2020.

Results

During the 2019/20 influenza season, 1,150,134 recipients of QIVc and 3,924,819, of QIVe-SD were identified following IPTW. In the main analysis, adjusted results show that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95%CI: 0.5%-9.9%]) and respiratory-related hospitalizations/ER visits (8.2% [95%CI: 6.5%-9.8%]). Similarly, in the HIAP analysis, QIVc was associated with a significantly higher rVE compared to QIVe-SD for influenza-related hospitalizations/ER visits (5.7% [95%CI: 0.8%-10.4%]) and respiratory-related hospitalizations/ER visits (7.3% [95%CI: 5.4%-9.2%]).

Conclusion

QIVc was more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits compared to QIVe-SD, using either a broad influenza season definition or restricting to the HIAP.

Disclosures

Victoria Divino, PhD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Stephen I. Pelton, MD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)
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

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

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< 0.05) and increased following vaccination for all 5 antigens (p< 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)
100. Safety Analysis of Live-Attenuated Measles, Mumps, Rubella Vaccine Among Hematopoietic Cell Transplant Recipients Vaccinated Within Two Years of Transplant
Authors: Mitre Xhoi , Feeley Monica , Sherman Amy C , Walsh Stephen R , Cheng Matthew , Kanjilal Sanjat , Ho Vincent T , Baden Lindsey R , Issa Nicolas C , Desjardins Michaël
Published: December 2021

Background

Measles, mumps and rubella (MMR) vaccine is a live-attenuated vaccine usually contraindicated within the first two years of hematopoietic cell transplant (HCT). During the 2019 measles outbreak at our center, the benefits of administering MMR vaccine within the first two years after HCT were weighed against the potential risks.

Methods

We conducted a retrospective review of patients who received MMR vaccination within two years of an autologous or allogeneic HCT. Patients’ demographics, date and type of HCT, underlying hematologic disease, type of immunosuppressive therapy and date of MMR vaccination were extracted from the electronic medical record. Adverse reactions that could be related to the vaccine were collected for up to 42 days post-vaccination and all hospitalizations and deaths following vaccination were reviewed.

Results

A total of 129 patients (75 autologous and 54 allogeneic HCT) were vaccinated between 300-729 days after HCT (median of 718 days). The median age at vaccination was 61 years old, 57% of the patients were male and 43% were on immunosuppressive therapy, 87% of whom were on maintenance therapy for multiple myeloma after auto-HCT. Seven patients (5%) had adverse reactions within 42 days of vaccination: six had respiratory tract infections (three with associated fever) and one had a rash leading to a brief hospitalization. This was a 37-year-old female who had an allogeneic HCT 542 days prior to MMR vaccination. She presented with a centrifugal maculopapular rash that was confirmed to be caused by the vaccine strain rubella virus (Fig 1). She fully recovered without sequalae. There was no other vaccine-associated illness identified in the cohort, after a median follow-up of 676 days.

Conclusion

MMR vaccine appears to be well tolerated in selected HCT recipients when given earlier than 2 years after transplant. No attributable severe outcomes or deaths were described. A mild uncomplicated case of vaccine-associated rubella illness was seen after vaccination. In the setting of a measles outbreak, assessment of potential risks and benefits of MMR vaccination given within two years of HCT remains important.

Disclosures

Stephen R. Walsh, MDCM, Janssen Vaccines (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Scientific Research Study Investigator) Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member) Sanjat Kanjilal, MD, MPH, GlaskoSmithKline (Advisor or Review Panel member) Nicolas C. Issa, MD, AiCuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)GSK (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)
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

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< 0.01), overall COVID-19-related fatality (2.3% vs. 1.0%; p< 0.01) and non COVID-19 related fatality (8.3% vs. 3.5%; p< 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

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

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

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 ( >60 min.) occurred before the surgical incision, if redosing was administered, and if prophylaxis was administered > 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 < 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 > 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)