bluuebunny/crossref_metadata_2025_split huggingface dataset:
697. 8 Years of Characteristics and Outcomes of Patients with MRSA Endocarditis Based on Vancomycin Minimum Inhibitory Concentration: Experience at a Tertiary Care Hospital
Authors: Alpizar-Rivas Rodolfo M , Balda Javier , Elarabi Salwa , Jaber Bertrand , Nader Claudia 
Published: January 2021

Abstract

Background
Vancomycin has been the mainstay of treatment for methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE). MRSA reduced susceptibility to vancomycin is a growing threat. Data assessing the effect of vancomycin reduced susceptibility on outcomes is limited. Our study aimed to evaluate characteristics and outcomes of MRSA-related IE based on the minimum inhibitory concentration (MIC) to vancomycin
Characteristics and outcomes of 51 patients with MRSA-related endocarditis according to the minimal inhibitory concentration (MIC) to vancomycin

Methods
IRB approval was obtained for a retrospective cohort study at a tertiary care center. Records of hospitalized adults diagnose with IE by ICD-9/ICD-10 CM codes were identified from 2011 to 2018. 51 patients had MRSA-related IE and were selected for the analysis. Demographic, microbiologic, Imaging and outcome variables were obtained. Characteristics and outcomes of patients with MRSA-related IE according to the MIC to vancomycin (≤ vs. &gt; 1 mcg/mL) were compared

Results
35.3% of patients had a MIC &gt; 1 mcg/mL. 59% were men, mean age was 46±3 years old. 65% acquired the infection through injection drug use. Only 3.9% of patients had prosthetic valve IE. 35.3% had tricuspid valve vegetation, 25.5% mitral valve and 21.6% aortic valve vegetation. Two patients had IE possibly related to a PICC-line infection; both of these patients had a MIC to vancomycin &gt;1 mcg/mL, suggestive of prolonged antibiotic therapy. All patients with MRSA-related IE were started empirically on vancomycin. Patients with a MIC &gt; 1 mcg/mL were more likely to be switched to a combination of daptomycin and ceftaroline, compared to those with a MIC ≤ 1 mcg/mL (44.4% vs. 6.1%; P=0.001). 25.4% underwent valvular replacement within 6 months. 12% died within 90 days. MRSA-related IE with MIC &gt; 1mcg/mL did not confer and an increase risk in in-hospital mortality (11.1% vs. 15.2%; P=0.67) or mortality at 90 days (11.1% vs. 12.5%; P=0.89).

Conclusion
In this single-center experience, we found that in 8 years 35% of patients with MRSA-related IE had MIC &gt;1 mcg/mL. This is an alarming finding. Although our study did not reach statistic significance we didn’t found difference in valvular surgery requirement or mortality among those with MIC &gt; 1mcg/d as compared to those with a more sensitive MRSA strain. A study with more power or a metha-analysis will be require to better answer this question.

Disclosures
All Authors: No reported disclosures
701. Blood Stream Infection And Risk Of Endocarditis Following Cardiac Valve Repair: A Population-Based Study
Authors: McHugh Jack , Khawaja Talha , Baddour Larry M , Baddour Larry M , Crestanello Juan , Arghami Arman , DeSimone Daniel , Sauver Jennifer St 
Published: January 2021

Abstract

Background
Bloodstream infections (BSIs) confer an increased risk of infective endocarditis (IE) in patients with a prosthetic cardiac valve. This relationship is less well established in patients undergoing valve repair. We conducted a retrospective population-based study to determine the incidence of BSIs following valve repair and identify risk factors associated with the development of IE.

Methods
The Rochester Epidemiology Project (REP) data linkage system was used to identify all persons who underwent valve repair in a 7-county region in Southeastern Minnesota between January 1, 2010 and December 31, 2018. Medical records were screened for the development of a BSI from time of procedure until May 15, 2020. Patients were classified as having BSI only, BSI with IE at outset, or BSI with subsequent development of new IE. IE at outset was defined as cases where IE was diagnosed at the time of initial positive blood culture.

Results
A total of 387 patients underwent valve repair surgery. A total of 31 (8%) patients subsequently developed a BSI, 4% within one year of surgery. Seventeen patients underwent mitral repair with annuloplasty, 9 underwent tricuspid annuloplasty, and 5 had concurrent repairs. Median time to the development of BSI was 338 days. Of the 31 patients with BSI, 4 (13%) had BSI with IE at outset. No patients developed IE subsequent to BSI, Enterococcus spp. was responsible for 3 cases of IE, and MSSA for 1. All cases occurred within one year of surgery. Given the low incidence, statistical analysis of associated risk factors for IE was not feasible. All patients with BSI and IE at outset, however, died by the end of the study period, versus 11/27 in the BSI only group.

Conclusion
Incidence of BSIs was higher in patients undergoing cardiac valve repair than in the general population. The incidence of IE with a BSI was 13%, which is lower than what has been previously published. It is notable that all cases of IE occurred within one year of surgery. Recognizing that endothelialization of device surfaces occurs, it is tempting to speculate that the risk of IE may be time dependent and may decline over time. Subsequent investigation of this theory is underway.

Disclosures
Larry M. Baddour, MD, Boston Scientific (Consultant)
705. Factors Associated with Local Invasion in Infective Endocarditis: a Nested Case-control Study
Authors: Ramanathan Abarna , Witten James , Gordon Steven M , Griffin Brian , Pettersson Gosta , Shrestha Nabin K 
Published: January 2021

Abstract

Background
A substantial proportion of infective endocarditis (IE) cases are complicated by local invasion. The purpose of this study was to identify patient and disease characteristics that increase the odds of local invasion in surgically treated IE patients.

Methods
This was a nested case-control study. All episodes of IE for patients admitted to Cleveland Clinic from January 1st, 2013 – June 30th, 2016 were identified from the Cleveland Clinic IE Registry. Patients &gt;18 years of age who underwent surgery for IE were included. Data was compiled by manual review of the Electronic Medical Record. Local invasion, defined as peri-annular extension, peri-valvular abscess, intra-cardiac fistula or pseudoaneurysm, was ascertained from the surgical operative note. Associations of selected factors with local invasion were examined in a multivariable logistic regression model.

Results
Among 510 patients who met inclusion criteria, 206 had local invasion. Mean age was 56 years and 369 (72 %) were male. Overall 344 (67 %) had aortic valve, 228 (45%) mitral valve, and 66 (13%) tricuspid or pulmonic valve involvement. Aortic valve involvement (OR 5.76, 95% CI 3.44 – 9.98), mechanical valve (OR 7.63, 95% CI 3.63 – 17.07), bioprosthetic valve (OR 3.20, 95% CI 1.99 – 5.19), significant paravalvular leak (OR 2.27, 95% CI 1.09 – 4.97), new atrioventricular nodal block (OR 3.05, 95% CI 1.57 – 6.09), Staphylococcus aureus infection (OR 2.11, 95% CI 1.20 – 3.76), coagulase negative staphylococcal infection (OR 2.38, 95% CI1.27 – 4.54), and non- viridans group streptococcal infection (OR 4.21, 95% CI 1.81 – 10.06) were significantly associated with local invasion.

Conclusion
Intra-cardiac and microorganism factors, but not comorbid conditions, are associated with local invasion in IE.

Disclosures
All Authors: No reported disclosures
706. Impact of Infectious Disease Consultation on Management and Clinical Outcomes of Infective Endocarditis: Results of an interrupted time series analysis
Authors: Okura Takayuki , Iwata Kentaro , Ohji Goh 
Published: January 2021

Abstract

Background
Infective endocarditis (IE) is associated with significant morbidity and mortality, and successful management requires expertise in both cardiac surgery and infectious disease (ID). However, the impact of ID consultation on clinical outcomes of IE is not clear.

Methods
The present study was a quasi-experimental, interrupted time series analysis of the clinical outcomes of patients with IE before (April 1998–April 2008) and after (May 2008–March 2019) the establishment of an ID department at a tertiary care hospital in Japan. The primary outcome was clinical failure within 90 days, defined as a composite of all-cause mortality, unplanned cardiac surgery, new-onset embolic events, and relapse of bacteremia caused by the original pathogen.

Results
Of 238 IE patients, 59 patients (25%) were treated in the pre-intervention period, and 179 patients (75%) were treated in the post-intervention period. Establishment of an ID department was associated with a 54% reduction in clinical failure (relative risk [RR], 0.46; 95% confidence interval [CI], 0.21–1.02; P=0.054) and a 79% reduction in new-onset embolic events (RR, 0.21; 95% CI, 0.07–0.71; P=0.01). In addition, the rate of inappropriate IE management significantly decreased (RR, 0.06; 95% CI, 0.02–0.22; P&lt; 0.01).
Segmented regression analysis for monthly rates of clinical failure.

Table 1. Comparison of the clinical characteristics of the patients between the pre-intervention and post-intervention periods

Table 2. Segmented regression analysis for primary and secondary outcomes

Conclusion
Establishment of an ID department at a tertiary care hospital was associated with improved management, better clinical outcomes, and reduced embolic events in patients with IE admitted to the hospital.

Disclosures
All Authors: No reported disclosures
722. Effectiveness of Fidaxomicin versus Oral Vancomycin in the Treatment of Recurrent Clostridioides difficile
Authors: Rinaldi Alyssa , Reed Erica E , Jessica Smith , Stevenson Kurt , Coe Kelci E 
Published: January 2021

Abstract

Background
The 2017 IDSA/SHEA clinical practice guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin.

Methods
This was a retrospective study evaluating inpatients with recurrent CDI treated with vancomycin or fidaxomicin between January 1, 2013 and May 1, 2019. The primary outcome was CDI recurrence. Secondary outcomes included re-infection, treatment failure, infection-related length of stay (IRLOS), and in-hospital all-cause mortality (IHACM). Data collected included demographics; number of previous CDI episodes; CDI therapy; time to recurrence and re-infection; exposure to broad-spectrum antibiotics, proton pump inhibitors, and probiotics. Wilcoxon rank sum, Pearson chi-square, or Fisher’s exact tests were utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted.

Results
One hundred thirty-five patients met inclusion criteria (n = 35 fidaxomicin vs. n = 100 vancomycin). Of these, 42 (31%) had experienced at least 2 CDI episodes prior to their index recurrence. There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p=0.18]; this persisted in the MLR model (OR 0.85 [95% CI 0.27-2.7]) and survival analysis (P = 0.1954). Additionally, there was no difference in re-infection rate (p=0.73), treatment failure (p=0.13), IRLOS (p=0.19), or IHACM (p=0.65).

Conclusion
Oral vancomycin and fidaxomicin are both suitable treatment options in the setting of recurrent CDI.

Disclosures
All Authors: No reported disclosures
724. Gastrointestinal (GI) PCR vs Stool Cultures: Impact on Length of Hospital Stay (LOS) and Antibiotic Use
Authors: Singh Vansha , Yune Philip , Rasul Rehana , Schwartz Rebecca , Niknam Negin , Khameraj Aradhana , Malhotra Prashant , Farber Bruce 
Published: January 2021

Abstract

Background
GI PCR can detect 22 pathogens (bacteria, parasites and viruses) from a single stool sample. Stool cultures are labor intensive and only target the most common diarrheal pathogens (such as Campylobacter, E. coli and a few parasites). We hypothesized that implementation of GI PCR would result in decreased LOS and lower antibiotic use.

Methods
This retrospective study utilized data from review of electronic medical records and included patients aged &gt; 18 years old who were admitted with diarrhea over a 3-year period from 2016 to 2019. LOS and antibiotic use data was collected for patients who had GI PCR from 2017–2019 (GIP arm) and compared with data from patients who had stool cultures from 2016–2017 (SC arm). Differences were assessed using Chi-square or Fisher’s exact test for categorical variables and the Mann Whitney Rank Sum test for continuous variables.

Results
The analysis included a total of 338 patients, 225 (66.6%) in the GI PCR arm and 113 (33.4%) in the SC arm. A significantly higher proportion of patients in the GIP arm had a positive result compared with the SC arm (26.2% vs. 9.7%, P &lt; .0001; Table 1). Table 2 shows the most frequently isolated organisms. Median LOS was 6 days (IQR: 4–13) for the GIP arm and 5 days (IQR: 3–7) for the SC arm (p=.060); 8 patients in the GIP arm had average LOS of 75 days due to comorbidities and disposition issues. However, within the GIP arm, median LOS was much shorter for patients detected with viruses by PCR vs. those with non-viral pathogens (3.5 days (IQR: 3-7) vs. 6 days (3-12)) There was no difference in antibiotic use between the GIP and SC arms (84.9% vs. 84.1%, P=.844). Patients in GIP arm were more commonly given Piperacillin-tazobactam and Carbapenems, whereas patients in the SC arm received metronidazole more often. Within the GIP arm, antibiotic use was lower among patients detected with viruses vs. those detected with non-viral pathogens (73.1% vs. 81.8%).
Table 1

Table 2

Conclusion
LOS was longer in patients in GIP arm vs SC arm, which may have been influenced by the presence of outliers in the GIP arm. No differences in antibiotic use was observed between the two groups. However, within the GIP arm, detection of viruses by GI PCR significantly shortened LOS and lowered antibiotic use.

Disclosures
All Authors: No reported disclosures
728. Prophylactic Vancomycin Therapy in Long Term Care Patients Colonized with Clostridioides difficile to Reduce Hospital-Acquired C. diff Infection
Authors: Muneer Sumayya , Sadlak Monika , Lobo Gitanjali , Brandt Dominique , Blatt Stephen P 
Published: January 2021

Abstract

Background
Clostridioides difficile (C. diff) is a common hospital-acquired infection with increasing rates of morbidity and mortality in elderly patients. Per the CDC, there are about 500,000 cases yearly in which 1 out of 11 patients die over the age of 65 due to complications from healthcare-associated C. diff infection (CDI). Oral Vancomycin has been shown to prevent recurrent CDI. Approximately 40% of patients admitted to Good Samaritan Hospital (GSH), who were colonized with C. diff developed active CDI while on antibiotic therapy during their hospitalization. In January 2017, GSH initiated a quality improvement intervention in which all patients admitted from long term care (LTC) facilities who were positive for C. diff colonization were given prophylactic oral Vancomycin with prescribed antibiotics.

Methods
This study is a retrospective cohort study within TriHealth facilities. The population included hospitalized patients from extended care, intermediate care, subacute rehabilitation, and nursing homes, who tested positive for C. Diff colonization from April 1, 2017, through June 30, 2018. Patients were screened for risk factors for C. diff. The primary outcomes were to determine whether patients developed CDI within 90-days of discharge and to evaluate for any events of CDI during their hospital stay.

Results
Among the 1,241 LTC patients who were admitted and screened for C. diff colonization, 213 (17%) were positive, 135 (63%) met inclusion criteria, and 5 (4%) patients who were admitted with CDI were excluded. 0% of patients treated with low dose Vancomycin developed CDI during their hospital stay, and a total of 5% of patients were found to have recurrent CDI within 90-day of hospital discharge. Patients who were already on antibiotics at the time of admission were at a higher risk of developing CDI (60% vs. 15%, p=0.034). Adherence to the study protocol was 78.5% and 19% of patients did not receive low-dose Vancomycin while on antibiotic therapy.
Image 1: Screening diagram to select patients for study

Table 1: Population characteristics

Conclusion
Review of CDI via TriHealth statistics revealed an overall reduction of hospital-acquired CDI since the implementation of prophylactic oral Vancomycin therapy. The next step will be to determine the duration of low dose vancomycin therapy for the prevention of future CDI as some patients did develop CDI within 90 days of discharge.
Image 2: C. diff infection rate throughout TriHealth facilities (Post Vancomycin prophylaxis)

Disclosures
All Authors: No reported disclosures
733. Ibrexafungerp Demonstrates Potent and Consistent In Vitro Activity Against &gt;400 Global Candida auris Isolates, Including isolates with Elevated MIC’s to Echinocandins
Authors: Borroto-Esoda Katyna , Angulo David A , Azie Nkechi 
Published: January 2021

Abstract

Background
Candida auris is an urgent global threat; a pathogen associated with high mortality (up to 60%), multi-drug resistance, the ability to spread from person-to-person and surface-to-person, presenting high risk for outbreaks in healthcare facilities. Echinocandins are the first-line treatment for patients with Candida auris infections given the high degree of resistance to azoles and polyenes. Ibrexafungerp is a novel IV/oral glucan synthase inhibitor (triterpenoid) antifungal with activity against Candida, Aspergillus and Pneumocystis spp, in Phase 3 development. We will present a compilation of &gt;400 Candida auris isolates from four studies, including 32 Candida auris isolates with elevated MIC’s to the echinocandins.

Methods
In vitro MIC data for ibrexafungerp against Candida auris isolates were compiled from across 4 independent studies with the majority of isolates originating in the US and India. In vitro susceptibility was determined by broth micro-dilution using CLSI (M27-S3) and/or EUCAST methods. Overall, 445 isolates were evaluated including 32 isolates with elevated MIC values to one or more echinocandins.

Results
The ibrexafungerp MIC90 value against the 445 clinical isolates was 1 μg/mL; the modal and MIC50 values were 0.5 μg/mL each. These results were consistent across the four studies and no differences were observed between MIC results generated using CLSI or EUCAST methods. Similar results were obtained for the 32 isolates with elevated MIC values to one or more of the echinocandins. Among this population, the mode, MIC50 and MIC90 were 0.5, 0.5, and 1 μg/mL, respectively. Only 1/32 of the echinocandin-resistant isolates had reduced sensitivity to ibrexafungerp (defined as &gt; 2-dilutions vs the mode). This isolate was pan-resistant with elevated MICs to all three echinocandins (MICs = 4 μg/mL) as well as fluconazole (MIC &gt;256 μg/mL) and amphotericin B (MIC = 1 μg/mL).

Conclusion
This data demonstrates that ibrexafungerp possesses potent and consistent in vitro activity against Candida auris and remains highly active against C. auris isolates with high MIC’s to the echinocandins.

Disclosures
Katyna Borroto-Esoda, PhD, SCYNEXIS, Inc. (Employee, Shareholder) David A. Angulo, MD, SCYNEXIS, Inc. (Employee, Shareholder) Nkechi Azie, MD, SCYNEXIS, Inc. (Employee, Shareholder)
750. Isavuconazole Cerebrospinal Fluid Concentration in Refractory Coccidioidal Meningitis - A Three-Patient Case Series
Authors: Davis Matthew R , Chang Sandy , Gaynor Pryce , McCreary Erin K , Allyn Paul R 
Published: January 2021

Abstract

Background
Coccidioidal meningitis (CM) causes life-threatening infection with limited treatment options. Small series have reported variable treatment success with isavuconazole. An absence of published data exists on cerebrospinal fluid (CSF) penetration of this agent.

Methods
Paired serum and CSF levels were measured on three patients with refractory CM treated on salvage isavuconazole therapy.

Results
11 CSF levels were sent on 3 patients; 7 from ventricular sources (Ommaya reservoir or external ventricular drain) and 4 from lumbar punctures at 6-44 days after treatment initiation, 2-24.6 hours after oral or intravenous dose. All levels sent from ventricular sources were undetectable &lt; 25µg/mL despite adequate paired serum levels (mean 2.45 µg/mL, range 1.25-6.38 µg/mL; n = 7 levels). Mean lumbar CSF levels were 1.00 µg/mL (range 0.45-1.72 µg/mL; n = 4 levels) with adequate serum levels (mean 3.57 µg/mL, range 1.78-5.63 µg/mL; n = 4 levels).
Table 1. Isavuconazole serum and cerebrospinal fluid concentration measurements

Conclusion
Isavuconazole was detected in lumbar, but not ventricular CSF in three patients treated for CM.

Disclosures
All Authors: No reported disclosures
751. Karius Cell-Free DNA Metagenomic Assay of Plasma Detects Pulmonary and Disseminated Trichosporon Infections in Patients with Hematological Malignancies
Authors: Chen Tempe , Ahmed Asim A , Goggin Kathryn , Wolf Joshua , Chu Julie , Pomputius Bill , Briggs Benjamin J , Sanacore Melissa , Solh Melhem M , Holland H Kent , Bashey Asad , Morris Lawrence , Solomon Scott , Webster Samuel , Walsh Thomas J 
Published: January 2021

Abstract

Background
Trichosporon species are uncommon but emerging pathogens that cause life-threatening infections that are resistant to amphotericin B and echinocandins. Diagnosis of deeply invasive trichosporonosis is often elusive to conventional culture methods until locally advanced or disseminated disease has advanced.
CT scans Pulmonary Trichosporonosis

Lung Bx of Trichosporon detected by Karius Cell-Free DNA Metagenomic Assay of Plasma

Methods
Review of cases of next-generation sequencing of microbial cell-free DNA from plasma using the Karius-based technology for establishing a diagnosis of invasive trichosporonosis

Results
We found that next-generation sequencing of microbial cell-free DNA from plasma using the Karius-based technology established a diagnosis in six pediatric and adult patients. The median age was 17 yrs (8-72 yrs) all patients had underlying acute leukemia myelogenous leukemia. Six patients had pulmonary nodules and two also had multiple cutaneous lesions with negative blood cultures. Biopsies of one pulmonary nodule and of two cutaneous lesions revealed yeast-like cells. Culture of cutaneous lesions in two patients grew Trichosporon sp. Karius assays performed on plasma and analyzed against a database of more than 300 species of fungi identified Trichosporon asahii in two cases, Trichosporon spp. in three, Trichosporon faecale in one. In all cases, the metagenomic results defined therapy for treatment of invasive trichosporonosis, which is based in antifungal triazoles. In one patient with pulmonary nodules, lung biopsy revealed mixed septate and non-septate hyphal elements that later grew Trichosporon asahii, Rhizomucor pusillus, and Candida parapsilosis, all of which were identified by Karius assay.

Conclusion
Invasive Trichosporon spp. are uncommon polyene and triazole-resistant pathogens that cause life-threatening invasive fungal disease resistant in immunocompromised patient with hematological malignancies; next-generation sequencing of fungal cell-free DNA by Karius-based technology identified all six cases of pulmonary and disseminated trichosporonosis, contributing to early detection and pathogen-directed antifungal therapy.

Disclosures
Asim A. Ahmed, MD, Karius (Employee) Joshua Wolf, MBBS, PhD, FRACP, Karius inc (Grant/Research Support)