bluuebunny/crossref_metadata_2025 huggingface dataset:
1136. Trends in Speaker Representation at the Infectious Diseases Society of America (IDSA) IDWeek Conference, 2013-2019
Authors: Marcelin Jasmine R , Khazanchi Rohan , Lyden Elizabeth , Cawcutt Kelly , Kullar Ravina , Kullar Ravina , Rajapakse Nipunie S , Ha David R , Ristagno Elizabeth H
Published: January 2021

Background

Over the last decade, there have been sustained efforts to diversify the healthcare workforce. In 2016, the IDWeek Program Committee was charged to ensure gender equity in speaker sessions. Whether this intervention also resulted in more opportunities for underrepresented speakers has not been determined.

Methods

This project was supported by IDSA, who provided demographic information on IDWeek speakers (excluding poster sessions) from 2013-2019. Data were summarized using descriptive statistics, and chi-square analysis evaluated changes over time. Each speaker slot was considered an independent event. Data was combined for 2013-2016 (≤2016) and 2017-2019 (>2016). IDSA membership demographics were available from 2014 for gender, race/ethnicity, from 2016 for age, and from 2018 for professional degree.

Results

A total of 3640 speaker slots were filled by 2504 individuals from 2013-2019. A larger proportion of speaker slots were filled by women >2016 (51%) vs ≤ 2016 (43%), with a linear increase from 38.6% in 2013 to 52.1% in 2019 (p< 0.001). Averaged across 2013-2019, IDSA membership was 67.5% White, 20.6% Asian, 7.7% Latinx, 3.9% Black, and 0.4% Other. IDWeek Speakers during that timeframe were 77.7% White, 13.9% Asian, 4.7% Latinx, 2.7% Black, and 1.0% Other; a larger proportion of slots were filled by Asian speakers >2016 (16.3%) vs ≤ 2016 (12.8%) (p=0.005). The proportion of pharmacist speakers increased over time; 5.1% of speakers in 2019 reflected IDSA pharmacist membership (5.4%). The proportion of individuals invited to speak more than once differed by age (19% in < 40yo, 28% 40-49yo, 32% 50-59yo, and 22% >60yo; p< 0.001), and professional degree (28% physicians, 18% pharmacists, 9% other doctorates, and 7% non-doctorate speakers; p< 0.001).

Figure 1: Trends in Gender Distribution of IDWeek Speakers and IDSA Members, 2013-2019

Figure 2: Trends in Race/Ethnicity Distribution of IDWeek Speakers and IDSA Members, 2013-2019

Conclusion

Intentional consideration of gender equity by the Program Committee significantly improved equitable gender representation of invited speakers at IDWeek. This effort has not resulted in increased diversity of invited speakers from groups underrepresented in IDSA membership. To ensure that invited speakers represent the membership of IDSA/IDWeek partner organizations and more importantly, the communities we serve, we call for continued application of the principles of Inclusion, Diversity, Access, and Equity at IDWeek.

Disclosures

All Authors: No reported disclosures
1137. What Do We Know? Teaching Medical Students to Deal with Uncertainty as a Pandemic Unfolds
Authors: Bauer Margaret E , Trujillo Daniel , Brown Cameron , Gomez Martiza , Davidson Darrell , Relich Ryan F , Allen Bradley L
Published: January 2021

Background

The global COVID-19 pandemic has had a major impact on medical student education. As the pandemic spread nationwide, numerous universities shut down with only days’ notice, and medical students were removed from all patient care settings and restricted from campuses. Yet, the need and curiosity of these future physicians to understand this new disease was great, including how to interpret and integrate rapidly evolving information on the underlying viral and immune mechanisms, pathophysiology, and epidemiology. Time students spent away from patient care settings presented an opportunity to rapidly develop and deliver new curriculum covering SARS-CoV-2 and COVID-19.

Methods

A team of students and faculty at Indiana University developed a Fundamentals of COVID-19 course that included up-to-date information on the virology, immunology, and pathophysiology of COVID-19. The course was delivered online, with both synchronous and asynchronous activities. Virology and immunology of the coronavirus family, including current knowledge to-date of SARS-CoV-2, were delivered using a series of readings and brief videos, followed by a small group exercise that required students to choose and present to their peers a paper from the scientific literature on COVID-19. A similar approach was used to deliver content about the pathophysiology of COVID-19. To place the COVID-19 experience in context of other pandemics, students researched and educated their small group cohort on another historical pandemic.

Results

To measure course effectiveness, we administered a pre-course survey gauging students’ self-confidence in their knowledge of these topics; the same survey was administered after completion of the course. Surveys from 645 (89% of enrolled) 3rd and 4th year medical students who completed both surveys were analyzed. Results showed that the course elicited a 57% increase (p< 0.001) in students’ confidence in their knowledge of COVID-19 virology and immunology and a 64% increase (p< 0.001) in knowledge of the pathophysiology.

Conclusion

Data showed that the asynchronous content and group activities were successful in engaging and educating the students on foundational knowledge of COVID-19 and were an effective approach to rapidly evolving information when faced with a novel disease.

Disclosures

All Authors: No reported disclosures
88. A Behavioral Economic Approach to C. difficile Testing Stewardship
Authors: Drees Marci , Winiarz Michael , Zhang Zugui , Dressler Robert , Eppes Stephen C
Published: January 2021

Background

To decrease inappropriate testing for C. difficile patients, we first employed an alert, followed by a hard stop (based on lack of documented diarrhea or laxative use), that could be overridden only by calling the laboratory. We describe a behavioral economic approach to test overrides that decreased the burden on both clinicians and laboratory staff without encouraging unnecessary testing.

Methods

Our 2-hospital, > 1200-bed community-based academic healthcare system has performed PCR-only C. diff testing since January 2015. We implemented our initial laxative alert, which did not prohibit testing, in March 2015. In April 2017, we launched a “hard-stop” alert that cancelled orders without documented diarrhea or recent laxative use. The provider could override by calling the laboratory and documenting the laboratorian’s name in the order; no further justification was required, but entries were intermittently monitored. In August 2019, we allowed clinicians to document their clinical justification instead of making this additional call, while emphasizing that rationales would be monitored for validity (Fig 1). We measured number of C. diff tests completed/month, overrides, and CDI standardized infection ratios (SIRs). We performed time-series analysis to account for each of these test ordering changes.

Figure 1: Image of C. diff alert

Results

At baseline, we observed a mean of 448 (SD, ±25) C. diff orders per month. The initial laxative alert led to a sustained decrease in monthly C. diff orders by 17% (p < 0.001; Fig 2). Another sustained decrease in monthly C. diff orders of an additional 29% (p< 0.001) occurred after the “hard stop” alert. Overall, C. diff orders decreased by 40% (3.5% per month). After introduction of the clinical justification documentation, to date we have not observed significant trends in C. diff override rates. The CDI SIR decreased from 0.9 (95% CI, 0.77- 1.04) in 2016 to 0.52 (0.42–0.64) in 2019.

Figure 2: Interrupted time series analysis

Conclusion

An iterative process to improve C. diff testing stewardship resulted in sustained improvements in C. diff ordering and hospital onset CDI cases. Behavioral economic approaches emphasizing the importance of clinical reasoning allowed us to reduce burden on clinicians and laboratory staff without increasing inappropriate testing.

Disclosures

All Authors: No reported disclosures
1152. Characteristics of Patients with Invasive Infections Caused by Trichosporon asahii
Authors: Kim Jinyeong , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Choi Sang-Ho , Lee Sang-Oh , Woo Jun Hee , Kim Yang Soo , Jung Jiwon
Published: January 2021

Background

Trichosporon asahii is main species for invasive infection by genus Trichosporon. There has been few data regarding the incidence, clinical characteristics, and treatment outcomes of T. asahii colonization and invasive infection.

Methods

We retrospectively reviewed the microbiological records of patients whose culture results were positive for T. asahii, from a tertiary hospital in South Korea between January 2009 and July 2018. Invasive disease was defined according to the consensus statement of the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC-MSG).

Results

During the study period, a total of 259 clinical T. asahii isolates (137 urine, 55 respiratory specimen, 26 blood, 16 surgical site drainage, 9 tissue biopsy, 9 open discharge, 3 toe/nail, 2 pleural fluid and 2 stool) were collected from 102 patients. Of the 102 patients, 18 (18%) had invasive infection: fungemia (12 [67%]), complicated skin and soft tissue infection (3 [17%]), pneumonia with or without empyema (2 [11%]), and complicated intra-abdominal infection (1 [5%]). Invasive infection was associated with hematologic malignancy (33% vs. 7%, P=0.006), end stage renal disease requiring dialysis (28% vs. 7%, P=0.02), indwelling central venous catheter (94% vs. 54%, P =0.001), and prior antifungal agent use (50% vs. 18%, P=0.01). Invasive group had significantly higher in-hospital mortality than non-invasive group (61% vs. 27%, P = 0.006).

Characteristics of 102 patients with invasive and non-invasive Trichosporon asahii disease

Conclusion

Invasive infection was associated with hematologic malignancy, end stage renal disease, indwelling of central venous catheter, and prior antifungal agent use, and high mortality up to 60%. Those with above risk factors should be monitored for development of invasive T. asahii infection.

Disclosures

All Authors: No reported disclosures
1154. Characterizing fungemic outcomes among adult inpatients at a community teaching hospital: a retrospective cohort study
Authors: Staicu Mary L , Laguio-Vila Maryrose R , Uzoma Joy , VanSice Ryan
Published: January 2021

Background

Fungemia is among the highest causes of mortality and length of stay (LOS) within the inpatient setting. We aim to characterize outcomes in adult inpatients with fungemia at our institution.

Methods

Adult inpatients with at least one positive blood culture with yeast between January 1st, 2017 and December 31st, 2018 were retrospectively identified via an electronic health record report. Outcome measurements were stratified into three categories: demographic, infectious, and antifungal-related.

Results

Forty-five patients were identified for review. The mean age was 62 years (SD 16.8) while the prevalence of fungemia among men and women was comparable (48.9 versus 51.1%). Diabetes (24.4%) and past malignancy (22.2%) were among the top comorbidities. One in five patients received total parenteral nutrition at the time of positive blood culture results. Central lines were present in 66.7% of patients and were implicated as the source of infection in the majority of cases (31%). Intensive care unit (ICU) admission, 30-day mortality, and 30-day hospital readmission occurred in 66.7%, 24.4%, and 26.7% of patients, respectively. The median time to culture positivity and time to antifungal therapy after positive culture results were 42.5 (IQR 36.5 - 63) and 6.5 hours (IQR 2.75 - 12.5), respectively. Candida albicans was found to be the primary fungal pathogen identified among cases reviewed, isolated in 53.3% of patients. ID consultation occurred in 86.7% of cases. Caspofungin was the predominant empiric antifungal agent prescribed (50.8%). Median total duration of therapy was 14 days (IQR 11.5 - 19).

Conclusion

This analysis successfully identified key high-risk areas of attention in the clinical management of adult inpatients with fungemia at our institution. Central lines and ICU admission were predominant characteristics identified, suggesting the complexity of the management of these patients. Although 30-day mortality and readmission rates were found to mirror current national averages for this population, further risk-assessment of these outcomes would be appropriate to evaluate in a larger study cohort.

Disclosures

All Authors: No reported disclosures
1156. Clinical and epidemiological features and outcomes of Blastomycosis in a tertiary hospital in Kentucky
Authors: Cari Evelyn Villacorta , Leedy Nicole , Ribes Julie A , Soria Jaime , Myint Thein
Published: January 2021

Background

Blastomycosis is an endemic dimorphic fungal infection caused by Blastomyces dermatitidis. The risk factors associated with severe presentation are not well defined.

Methods

Retrospective study of patients treated for blastomycosis at the University of Kentucky Hospital from 2004-2019. Statistical analyses were performed with STATA version 12.0 (College Station, Texas). Logistic regression was used to identify variables associated with severe infections.

Results

Among 82 patients, median age was 48 years old (range: 16 - 89); 66 (80.5%) were male and 71 (92.2%) were white, 25/77 (32.4%) were obese, 24 (29.2%) were diabetic, 21 (25.6%) had COPD, 26 (31.7%) had at least one immunosuppressive condition. The median duration of illness was 86 (3-365) days. 37 (45.1%) had cough and 35 (42.6%) had dyspnea 19 (23.1%) patients were treated in the ICU, 42 (51.3%) in non-ICU inpatient wards, and 21 (25.6%) in an outpatient setting. Cultures were obtained in 69 cases, 59 (85.5%) reported as positive, KOH stain positive in 30/61 (49.1%). Histopathology was positive in 48/66 (72.7%) samples. Urine Histoplasma or Blastomyces antigen was positive in 41/58 (70.6%), and Serum Histoplasma or Blastomyces antigen was positive in 22/34 (64.7%). Among 64 (78.0%) patients with pulmonary blastomycosis, acute and chronic pneumonia were 16 (25.0%) and 12 (18.7%) cases respectively, and nodular lung lesions were reported in 36 (56.2%). Initial antifungal treatment was amphotericin B liposomal in 38/80 (47.5%), overall mortality was 11 (13.4%). A multivariable analysis was performed to find predictors of severe blastomycosis infection, no association was seen with factors as male sex (IRR 1.96; 95%CI 0.84 – 4.55), and was confirmed that significant independent associated risk factors for severe infection were age older than 50 (IRR 3.5; 95%CI 1.42-8.83), obesity (IRR 3.1; 95% CI 1.41-6.87), diabetes (IRR 2.5; 95% CI 1.16-5.50), leukocytosis (IRR 1.03; 95%CI 1.00-1.07) and anemia (IRR 3.0; 95% CI 1.55-5.85).

Conclusion

Pulmonary Blastomycosis is the most common presentation. Culture and histopathology are more sensitive than antigen assay. Independent factors associated to severe disease were older age, obesity, diabetes, and anemia at admission.

Disclosures

All Authors: No reported disclosures
1159. Echinocandins Dosing in Obese Patients: A Systematic Review
Authors: Alsowaida Yazed S , Pharm B S , Almulhim Abdulaziz S , Kalbasi Alireza
Published: January 2021

Background

Echinocandins are a milestone in antifungal chemotherapy given their fungicidal properties with improved toxicity profiles compared to other antifungal agents. Echinocandins are used in the empiric treatment of invasive candidiasis and aspergillosis in critically ill, neutropenic, and transplant patients. There is emerging evidence that obese patients treated with echinocandins antifungal agents have lower plasma serum concentration and faster clearance. The objective of this review was to systematically evaluate the available evidence for echinocandins dosing in obese patients.

Methods

A systematic review of PubMed, Embase, Cochrane library from inception until June 8, 2020 was conducted by 2 authors. Studies with data for micafungin, anidulafungin, or caspofungin in obese patients’ exposure [body mass index (BMI) 30 or greater] were included. Studies for patients on renal replacement therapies, extracorporeal membrane oxygenation support, and language other than English were excluded.

Results

Twenty-five studies met the inclusion criteria; micafungin (n=10), caspofungin (n=8), and anidulafungin (n=7). In micafungin, the correlation between obesity and increasing systemic clearance and reduced exposure was reported. Some studies reported even lower systemic exposure with morbid obesity, BMI greater than 40. The evidence was also consistent with anidulafungin, two studies revealed that body weight had inverse correlation with anidulafungin exposure. Anidulafungin exposure was about 30% lower in obese patients. Furthermore, caspofungin exposure was also reduced in obese patient as demonstrated in several studies.

Conclusion

Adequate antifungal exposure is a key in success treatment, and there are several factors that can influence exposure of echinocandin antifungal agents. There is consistent evidence revealing lower echinocandins exposure in obese patient. Research is needed to determine outcomes of fungal infections of obese patients, and perhaps the need for dose adjustment in obese patient population.

Disclosures

All Authors: No reported disclosures
1171. Lower Mortality with Adjuvant Corticosteroid Therapy in non-HIV Infected Patients with pneumocystis jirovecii pneumonia: A Single US Cohort Study and a Proposed Novel Mechanism of Corticosteroids
Authors: Mundo William , Franco-Paredes Carlos , Johnson Steven C , Shapiro Leland , Henao-Martinez Andres
Published: January 2021

Background

Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids given at the time of PJP antimicrobial therapy in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients, and to propose a novel mechanism explaining corticosteroid benefit in patients regardless of HIV status.

Methods

We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality.

Results

Underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). Compared to HIV-positive patients, HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. In a novel model of adjunct corticosteroid benefit, we propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents.

Table 1. Multivariable Analysis of Predictors of Mortality in patients with PJP

Figure 1. Mortality differences by HIV status and use of steroids in PJP

Conclusion

We found substantial mortality among HIV-negative patients with PJP and adjunct corticosteroid use was associated with decreased mortality. Adjunct corticosteroid mortality-lowering effect is best explained by suppressing pneumocystis lysis. This reduces surfactant disruption resulting from pneumocystis internal substances.

Figure 2. Proposed mechanism of action for benefits of adjunct exogenous corticosteroid therapy during PJP

Disclosures

All Authors: No reported disclosures
91. Implementing Criteria to Reduce Blood Cultures Ordering: A Pre- and Post-Intervention Retrospective Study in a Critical Access Hospital
Authors: Mahatanan Rattanaporn , Gomez Gina , Olsen Bridget , Henderson Racheal
Published: January 2021

Background

Blood culture utilization has been performed widely. Typically, clinicians order blood cultures in patients whom bacteremia is suspected. Our previous study showed that 35% of blood cultures performed in May 2019 could have been prevented since they did not meet the certain criteria. This study sought to examine the outcomes after education intervention by implementing criteria of blood culture ordering whether it could reduce unnecessary blood cultures.

Methods

Electronic medical records of adult patients who had blood cultures done during pre-and post-study period were reviewed. Demographic data, clinical presentation, vital signs, location, quantities and sites of blood cultures were obtained. The measurement of qSOFA, SIRS and severe sepsis criteria were collected on the presentation. There were some clinical prediction rules for blood stream infection described in the previous studies. For this study, we use the criteria of at least 2 SIRS and/or at least one of the qSOFA criteria or severe sepsis to be a minimum indication for ordering blood cultures. The follow-up study was done after 6 weeks of educational intervention with implementation of criteria. Chi-square was used to compare the differences between two groups.

Results

There were a total of 165 patients included in our study (112 in pre- and 53 in post-intervention group). There were a total of 18 patients with positive blood cultures (12/112;10.71% in pre-intervention gr. vs 6/53;11.32% in post-intervention gr., p=0.91). Six out of 18 (33%) were deemed to be contaminated (3/12;25% vs 3/6;50%, p=0.29). Gram positive cocci were the most common organisms of the true positive blood cultures (10/12;83%). Of 165 patients, 78 (47%) had at least one of qSOFA (47/112;41% vs 31/53;58%, p=0.05), 18 (11%) had met severe sepsis criteria (9/112;8% vs 9/53;17%, p=0.09). There were 47 (28%) patients who had less than 2 criteria of SIRS and did not meet either criteria of qSOFA or severe sepsis (39/112; 35% vs 8/53; 15%, chi 6.87, p< 0.01). There was no true bacteremia in this group of patients.

Conclusion

Our study found that implementation of criteria for blood cultures successfully reduces the unnecessary blood cultures orders approximately 20% without missing true bacteremia in suspected patients.

Disclosures

All Authors: No reported disclosures
1174. Phase 2 STRIVE Clinical Trial of Rezafungin for Treatment of Candidemia and/or Invasive Candidiasis Demonstrates Consistent Trough Concentrations Across Diverse Patient Populations
Authors: Flanagan Shawn , Rubino Christopher M , Sandison Taylor
Published: January 2021

Background

Rezafungin is a novel echinocandin antifungal in development for treatment as well as prevention (prophylaxis) of invasive fungal infections. STRIVE (NCT02734862) is a global, randomized, double-blind, placebo-controlled, Phase 2 trial evaluating safety and efficacy of IV rezafungin once weekly (QWk) for treatment of candidemia and/or invasive candidiasis compared with standard-of-care (IV caspofungin once daily with optional oral stepdown). Here we report pharmacokinetic (PK) data from the completed STRIVE trial analyzed by patient demographics at baseline.

Methods

Rezafungin Day 8 trough (Cmin) concentrations from patients treated with rezafungin were summarized categorically by race (black or white), sex (male or female), and geographic region (North America [NA], or Europe [EU]), or plotted versus continuous variables of age, body weight, body mass index (BMI), and body surface area (BSA). As the first dose of rezafungin was 400 mg for all rezafungin-treated patients, data from both dose groups (Group 1: 400 mg QWk; Group 2: 400 mg in Week 1 followed by 200 mg QWk) were combined in this analysis.

Results

Rezafungin mean Cmin (SD) values were 1.8 (0.7) and 2.3 (1.2) in black and white patients, 1.9 (1.0) and 2.6 (1.2) in males and females, and 1.9 (0.6) and 2.4 (1.3) in patients from NA and EU. There were small differences in point estimates between the groups, but there was a great deal of overlap and the differences are not expected to be clinically meaningful (Figure). Similarly, no trends in Cmin values were observed across a range of ages (20-80 years), weights (~40-155 kg), BMI (~15-65 kg/m2), and BSA (~1.4-2.4 m2).

Figure

Conclusion

No meaningful differences in rezafungin Cmin values were observed in patients grouped by sex, race, or geographic region, or across a wide range of patient factors, including age and body weight and size. These findings indicate that a single rezafungin dose regimen can be expected to provide consistent PK across diverse patient populations.

Disclosures

Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Christopher M. Rubino, PharMD, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)
1176. Quality of Life of Previously Healthy Subjects following Cryptococcal Meningoencephalitis
Authors: Dean Owen , Anjum Seher , Scott Terri , Ham Lillian , Powers John H , Snow Joseph , Williamson Peter
Published: January 2021

Background

Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in HIV-negative, previously healthy populations. This group has significant disease sequalae including a fronto-subcortical syndrome, hearing loss, vision loss, and spinal arachnoiditis. However, the health-related quality of life (HRQOL) of this group of patients following microbial recovery from infection has not been reported.

Methods

We cross-sectionally defined the HRQOL of previously healthy individuals with CM seen at the NIH Clinical Center since 2013 and at least one year past diagnosis using the Quality of Life in Neurological Disorders (Neuro-QoL) project short forms. These forms assess domains such as anxiety, fatigue, depression, dexterity and mobility in patients with chronic neurological disease. Form scores were calculated for each domain and centered to a general or clinical United States population reference. Impairment was considered a subject score of least one half a standard deviation (SD) lower than the population reference average.

Results

Of 43 subjects with CM (mean age 48 years, 56% male, mean time from diagnosis 5.7 years), 91% had evidence of impairment in at least one HRQOL domain. Notable findings included self-reported impaired cognitive function in 53% and sleep disturbance in 56%. Impaired satisfaction with social roles and activities was present in 44%. Mobility and dexterity were impaired in 30% respectively. The number of impaired HRQOL domains was not significantly different in subjects with a history of neurosurgical intervention during hospitalization (mean no. impaired domains 4.4 vs. 3.3, P=0.43) or methylprednisolone treatment for post-infectious inflammatory response syndrome (4.3 vs. 3.4, P=0.63). Cerebrospinal fluid glucose levels on admission were negatively correlated with the number of impaired functional domains (rs=-0.33, P=0.05, n=38).

Patient reported quality of life domains following microbial recovery from cryptococcal meningoencephalitis. Box plots show median, 25th, and 75th percentiles.The gray dotted line represents the mean T-score (50) of the U.S. population reference for each Neuro-QoL domain. The yellow region designates mild symptoms or impairment (0.5-1.0 std below the population mean), orange, moderate (1.0-2.0), and red, severe (2.0-3.0). The asterisk* indicates measures that were centered to U.S. clinical reference population. All other domains were centered to a U.S. general population reference. Abbreviations: CNS, central nervous system, U.S., United States, ADL, activities of daily living, SRA, social roles and activities

Conclusion

This is the first report of HRQOL deficits in previously healthy individuals following microbial recovery from CM. These data reinforce and quantify the long-term morbidity of this disease and identify patient-centered outcomes for future interventional trials.

Disclosures

All Authors: No reported disclosures
1180. Seroincidence and Risk of Coccidioidomycosis Infection Among Active Duty Personnel Stationed at Naval Air Station Lemoore in the San Joaquin Valley of California
Authors: Ellis Graham C , Lanteri Charlotte , Hsieh Hsing-Chuan , Graf Paul , Sanders Terrel , Maves Ryan C , Deiss Robert
Published: January 2021

Background

Coccidioidomycosis ranges clinically from a self-limited respiratory illness to multi-organ dissemination. Based largely on skin testing from the 1940s, 60% of infections are thought to be asymptomatic. Limited Coccidioides seroincidence data support our understanding of the epidemiology and pathogenicity of this disease.

Methods

This retrospective cohort study tested 2000 U.S. military personnel for Coccidioides exposure after transfer to an endemic region of California between 2011 and 2017. The presence of IgG and IgM anti-Coccidioides antibodies were tested on pre- and post-transfer serum samples from the DoD Serum Repository to establish rates of seroconversion. Medical histories and participant demographics including race/ethnicity and military occupational specialty codes were collected from the electronic medical record and participants were stratified by a history of Coccidioides-specific or general respiratory illness based on ICD9/ICD10 coding.

Results

Thirty of 2000 participants tested newly positive for anti-Coccidioides antibodies after 12 months on station. Seroconversion incidence varied from 0.0-1.32 annually and overall 0.5 per 100 person years. Seroconverters were more frequently diagnosed with coccidioidomycosis or pneumonia than non-converters (p=0.027). No statistically significant association between demographic characteristics and seroconversion or disease was observed. Clinical disease was detected in only three seroconverters (10%).

Incidence Rate of Coccidioidomycosis Infection among Active Duty Stationed at NAS Lemoore, 2011-2017

Seroconversion Status by Cocci/Pneumonia Diagnosis Status

Conclusion

In this study Coccidioides seroincidence was similar to that observed by others, adding longitudinal evidence to epidemiologic assumptions about coccidioidomycosis. A trend toward increasing incidence over the course of the study is consistent with the classification of coccidioidomycosis as an emerging infectious disease. While transmission is typically related to exposure, we did not detect a difference based on military occupational specialty codes. Overall, rates of diagnosed disease in our cohort were lower than the historically-assumed 40% symptomatic rate, although this conclusion is limited by the retrospective nature of the study. Further clinical and epidemiologic coccidioidomycosis research, particularly in broader endemic regions, is warranted.

Disclosures

All Authors: No reported disclosures
1181. Spectrum and Risk Factors of Early Onset versus Late Onset Neonatal Candidemia from Pakistan
Authors: Rattani Salima , Jabeen Kauser , Farooqi Joveria , Hussain Ali Shabbir
Published: January 2021

Background

Candidemia leads to high morbidity and mortality especially in premature neonates from developing countries. We studied the spectrum and risk factors of candidemia in neonates with early onset disease (EOD) or late onset disease (LOD) which has not been extensively investigated in Pakistan. We also determined whether vaginal delivery is associated with candidemia in neonates with EOD.

Methods

A case control study was conducted at the Aga Khan University, Karachi, Pakistan. Cases (neonates with EOD) and controls (neonates with LOD) were identified from laboratory database for year 2014-2018, and for 2019 data was collected prospectively from laboratory during routine reporting of cultures at which time clinical information was gathered from the patient’s physician/guardian. Study was conducted after obtaining exemption from the ethical review committee.

Results

A total of 669 neonates with IC were identified, out of these 162 neonates had EOD while 507 had LOD. Chart 1 shows the year wise distribution and frequency of different C. species. Mean age of neonates with EOD and LOD was 1.7 and 12.2 days respectively. LOD in neonates was more likely to occur in male patients (COR 2.5, 95% CI 0.6-9.9) was and associated with use of carbapenems (COR 5.1, 95% CI 1.4-17.8). However, LOD had no correlation with non-C. albicans Candida sepsis (COR 0.6, 95% CI 0.1-6.3) as causative agent. EOD was more likely in patients delivered via vaginal delivery (COR 11.3, 95% CI 2.6-48.5).

Chart 1: Year wise distribution of Candida species in neonates with candidemia from 2014-2019

Conclusion

The trends for isolation of C. species in neonates showed a trend with C. tropicalis being more common C. species during the recent years. With the infrequent isolation of C. glabrata and C. krusei among other Candida species in this study, fluconazole may be considered a good empiric choice for neonates with suspected fungal sepsis.

Disclosures

All Authors: No reported disclosures
1183. A Prospective Epidemiological & Immunological Study of Cytomegalovirus infection in SLE Patients Receiving Immunosuppressant
Authors: Autto Suphanan , Pisitkun Prapaporn , Apiwattanakul Nopporn , Bruminhent Jackrapong
Published: January 2021

Background

Cytomegalovirus (CMV) infection has been emerging among autoimmune disease patients. CMV-specific cellular immunity has been shown to be correlated with CMV clearance in transplant recipients, however, this correlation has not been assessed in autoimmune disease patients. We aimed to investigate the epidemiology and clinical variables of CMV infection focused on CMV-specific cellular response of CMV infection in active systemic lupus erythematosus (SLE) patients receiving immunosuppressant.

Methods

A prospective cohort study of active SLE patients who received immunosuppressant and underwent preemptively monitored for CMV infection by quantitative real-time PCR (Abbott RealTime CMV assay). Clinical variables were collected. CMV-specific cellular immune responses were measured by an enzyme-linked immunosorbent assay (QuantiFERON-CMV®) and intracellular cytokine assay. Clinically significant CMV infection was defined as CMV disease or plasma CMV DNA loads > 1,000 IU/mL.

Results

We included 45 active SLE patients in our cohort. Among 39 evaluable patients, there were 36 (92%) female patients with a median age of 28 (IQR 24-44) years. A median SLEDAI score was 16 (IQR 9-20). Seventy-four % had renal involvement. Methylprednisolone was the most common immunosuppressive regimen (94.9%). Thirty-six (92.3%) patients were CMV-seropositive. Clinically significant CMV infection occurred in 6 (25.6%) patients included asymptomatic CMV infection (79.3%), CMV syndrome (17.3%), and CMV tissue invasive disease (3.4%). Among 197 blood samplings, there were 16 (8.1%) episodes of clinically significant CMV infection. The distributions of QuantiFERON-CMV® status were reactive, non-reactive and indeterminate (33% vs. 44% vs. 22%; p = 0.56), respectively. The percentage of CMV-IE1-specific NKT cells in those with clinically significant CMV infection were lower than those without infection (0.18% vs. 1.93%, p = 0.03). In multivariate analysis, neurological involvement was associated with clinically significant CMV infection (OR 7.9; 95% CI 1.5-41.9, [p = 0.015]).

Conclusion

Active SLE patients with neurological involvement who received intense immunosuppression are at risk of CMV infection. Lack of CMV-specific NKT cell response tends to be associated with CMV infection.

Disclosures

All Authors: No reported disclosures
92. Utility of Sinus CT in the Evaluation of Patients with Febrile Neutropenia
Authors: Gurram Pooja , Almeida Natalia E Castillo , Vijayvargiya Prakhar , Grimont Christopher , Garrigos Zerelda Esquer , Khalil Sarwat , Ward Ruaa Al , Mahmood Maryam , Sohail M Rizwan
Published: January 2021

Background

The etiology of febrile neutropenia in patients with hematological malignancy is identified in only 20–30% of cases. Sinus computed tomography (CT) is often used, regardless of symptoms, to rule out rhinocerebral source of infection. There are no clear guidelines on when to perform sinus CT in this population. In this study, we evaluated the role of sinus CT in febrile neutropenic patients.

Methods

We retrospectively reviewed medical records of all adults (age ≥18 years) with febrile neutropenia (T≥ 38.3ºC, ANC < 0.5 x 109/L) and hematological malignancies who underwent sinus CT from January 2014 to May 2020. We present the preliminary analysis of the impact of sinus CT findings on the management of febrile neutropenia.

Results

47 patients with a total of 56 episodes of febrile neutropenia met the inclusion criteria. The median age at presentation was 57 years (IQR: 42 - 68 years). The most common underlying malignancy was acute myeloid leukemia (51%), followed by myelodysplastic syndrome (19%). At presentation, 47% had refractory disease, 21% were newly diagnosed, 15% had relapsed, 15% were in complete remission, and 2% were in partial remission. Of the total 56 episodes, 29 (52%) had symptoms of rhinorrhea (20%), facial pain (14%), and sinus congestion (14%). The remaining 27 of 56 episodes (48%) had no sinus symptoms. Sinus CT was abnormal in 48 of 56 episodes (86%); the most common finding was mucosal thickening (47/48; 98%), followed by air-fluid levels (7/48; 14.5%), partial opacification (6/48; 12.5%), complete opacification (2/48; 4%), and bony invasion (2/48; 4%). The source of febrile neutropenia was attributed to the CT sinus findings in 9 cases (9/48; 29%), leading to a change in therapeutic management. All 9 patients were symptomatic, with evidence of necrosis in 22% (2/9) and purulence in 22% (2/9) on nasal endoscopy.

Table 1

Conclusion

Mucosal thickening is a frequent and non-specific imaging finding, particularly in patients without sinus symptoms. Sinus CT findings in patients with febrile neutropenia without sinus symptoms had no impact on clinical management. Consequently, sinus CT may be reserved for patients presenting with sinus symptoms.

Disclosures

M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)
1190. Dual-Plasmid Technology for Precision Genome Editing in Staphylococcus aureus
Authors: Reish Jennifer , Dey Somrita , Penewit Kelsi , Salipante Stephen J , Berti Andrew David
Published: January 2021

Background

Genetic manipulation of Staphylococcus aureus (both methicillin sensitive S. aureus, MSSA, and methicillin resistant S. aureus, MRSA) poses a technical challenge due to poor transformation efficiency, limited endogenous DNA repair activity, lineage-specific methylation patterns and intrinsic resistance to common selectable markers.

Methods

To address transformation efficiency we have optimized electrocompetent cell preparation and electroporation protocols for staphylococci. Further, we have improved a CRISPR counterselection platform that delivers a heterologous ssDNA recombinase and an inducible Cas9 endonuclease. When used for recombineering and counterselection, this strategy allows minimization of the number of elements necessary to transform in a single electroporation event. The Cas9 delivery platform has been modified to include a range of selectable markers including resistance to apramycin, erythromycin, kanamycin, nourseothricin, spectinomycin or trimethoprim.

Results

Overall electroporation efficiency increased by multiple orders of magnitude (> 100×) using the optimized cell preparation protocol. The CRISPR delivery platform can be stably maintained in a repressed state for multiple generations and induced with anhydrotetracycline. We have introduced targeted mutations in multiple loci using this system with an average turnaround time of 12 days.

Conclusion

This improved dual-plasmid CRISPR platform is robust and allows the investigator to rapidly and specifically alter the genomes of staphylococci. These tools will facilitate the study of how specific genetic polymorphisms contribute to various phenotypes in S. aureus, including the virulence of MRSA.

Disclosures

All Authors: No reported disclosures
1193. Human Transcriptomic Analysis of Periprosthetic Joint Infection
Authors: Masters Thao , Bhagwate Aditya , Dehankar Mrunal , Greenwood-Quaintance Kerryl , Abdel Matthew P , Patel Robin , Patel Robin
Published: January 2021

Background

Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure.

Methods

We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure.

Results

Differential gene expression analysis confirmed the association of 28 previously investigated biomarkers with PJI- bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), chemokines CCL3, CCL4, and CXCL2, colony stimulating factor 2 receptor (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), receptor CD64B, intercellular adhesion molecule 1 (ICAM1), IFNG, IL13RA2, IL17D, IL1A, IL1B, IL1RN, IL2RA, IL2RG, IL5RA, IL6, IL8, lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), as well as identified three novel molecules with diagnostic potential for detection of PJI- chemokine CCL20, coagulation factor VII (F7), B cell receptor FCRL4. Comparative analysis of infections caused by staphylococcal versus non-staphylococcal and Staphylococcus aureus versus Staphylococcus epidermidis showed significant elevated expression of IL13, IL17D, and metalloprotease protein MMP3 in staphylocococcal infections, and increased expression of IL1B, IL8, and platelet factor PF4V1 in S. aureus infections. Pathway analysis of over-presented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents.

Conclusion

Our study provides new potential targets for diagnosis of PJI and targets for differentiation of PJI-associated infectious agents.

Disclosures

Matthew P. Abdel, MD, Dr. Abdel receives royalties from Stryker on certain hip and knee products, and is a paid consultant for Stryker. (Consultant) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)
1196. Influence of antibiotic use on the effectiveness and safety of immune checkpoint inhibitors in Japan
Authors: Minamishima Takuya , Hida Hirotake , Yamada Kiyofumi
Published: January 2021

Background

It has been reported that antibiotic use changes the gut microbiome and alters the outcome of treatment with immune checkpoint inhibitors (ICIs). However, in Asia, this has not been well studied, and there is insufficient evidence to support these reports.

Methods

In this study, we investigated the concurrent use of antibiotics and the administration of PD-1 inhibitors in Japanese patients, and examined the relationship between antibiotics and the clinical benefit or safety of PD-1 inhibitors.

Results

In total, 152 patients were analyzed: 62 patients received systemic antibiotics within 2 months before or 1 month after the first dose of PD-1 inhibitors (the antibiotic group); the remaining patients comprised the non-antibiotic group. There was a significantly higher proportion of patients under 65 years of age in the antibiotic group. Overall survival (OS) was not reached in the antibiotic and non-antibiotic groups, and there was no statistically significant difference between the two groups (HR = 1.48) (Figure 1). Progression-free survival (PFS) was 3.29 months in the antibiotic group and was significantly shorter than that in the non-antibiotic group (5.99 months, HR = 1.75) (Figure 2). Multivariate analysis by Cox regression analysis also showed that PFS was shorter in the antibiotic group (HR=1.63). As age may be a confounding factor, we performed a stratified analysis, a common method used to adjust for bias. The results of the stratified log-rank test after adjustment for age showed that the PFS was significantly shorter in the antibiotic group. There were no statistically significant differences between the two groups in the response rate, incidence of adverse events of Grade 3 or above, and laboratory data (Table 1).

Figure 1

Figure 2

Table 1

Conclusion

Our results suggest that the use of antibiotics may affect the anticancer treatment outcomes of Japanese patients who are administered PD-1.

Disclosures

All Authors: No reported disclosures
1197. Inhibitory Effect of Ursodeoxycholic Acid on Clostridioides difficile Growth
Authors: Alnezary Faris , Alam M Jahangir , Almutairi Masaad , Fallatah Saad , Begum Khurshida , Gonzales-Luna Anne J , Garey Kevin W
Published: January 2021

Background

Ursodeoxycholic acid (UDCA), a secondary bile acid, inhibits germination and growth of Clostridioides difficile in vitro, but the results from in vivo experiments have been conflicting. We evaluated the effects of UDCA on C. difficile in vitro and in a wax moth, Galleria mellonella model.

Methods

The in vitro growth and germination effects of UDCA on C. difficile were assessed with increased concentration of UDCA (0.001, 0.01, 0.05, and 0.1%). To assess treatment effects of UDCA, C. difficile spores (approximately 1x10^6-8 colony forming units (CFU)) were force fed to G. mellonella larvae treated with UDCA (50 mg/kg/day) 24 hours prior to C. difficile inoculation. Forty G. mellonella larvae were used for each experiment, which was repeated with two distinct strains (R20291 and CD196). Larvae were housed at 37°C and monitored for the next five days for mortality.

Results

In vitro experiment demonstrated inhibition of C. difficile growth at 0.1% concentration (P < 0.001 vs control). Larvae treated with UDCA had a numerically higher survival rate (60% / 24/40) compared to controls (40% / 16/40) but the results were not statistically significant (p=0.14). Identical rates of survival were observed in the control arms for both strains (40%) and similar in the treatment arms (R20291: 70%; CD 196: 50%).

Conclusion

Overall, UDCA shows inhibitory effect of growth and germination of C. difficile in vitro. However, in our G. mellonella model, a single dose of UDCA given prior to infection did not prevent CDI. Further dose dependent, and multiday studies investigating the role of UDCA in CDI is needed to better understand this in vitro / in vivo paradox.

Disclosures

Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)