bluuebunny/crossref_metadata_2025 huggingface dataset:
684. The impact of rapid molecular respiratory testing on provider and parental decision making for children with respiratory illness evaluated in an ED setting
Authors: Rao Suchitra , Moss Angela , Lamb Molly , Mistry Rakesh , Dominguez Samuel
Published: January 2021

Background

Rapid respiratory testing (RRT) can decrease ancillary testing, length of stay and antibiotic use for hospitalized children. Less is known regarding the impact of RRT in the emergency department (ED).

Our objectives were to determine if RRT impacts ED provider clinical decision making, family acceptance, and subsequent healthcare visitation for children with influenza-like illness (ILI).

Methods

Randomized controlled trial of children 1 month-18 years of age presenting to a tertiary care pediatric ED with ILI. All children received a nasopharyngeal swab and RRT and were randomized to the intervention group (RRT result given to clinicians/families) or control group (results not available unless obtained clinically). Outcomes included provider decision-making (anti-infective prescribing, ED diagnostic testing, disposition), family acceptance of RRT (willingness to undergo future testing) and repeat healthcare visits (clinic or ED). Providers in the intervention group were surveyed after RRT results were available, and families in both arms were contacted 1 and 10 days later.

Results

There were 920 ED visits from 908 enrolled children; 629 (68%) families from both arms and 443 (96%) providers from the intervention arm completed surveys. Most providers (33%) were ED trained and < 5 years post-training (37%). Clinical decisions were changed in 17% of visits based on RRT results, most commonly by ED trained physicians, advanced practice providers, and those < 5 years post-training (Table). The most common decision changes were antiviral use and avoidance of diagnostic tests (Figure). Families were more willing to undergo future RRT if they were in the intervention group, or if RRT results were available in 20 minutes. In the control arm, 22 families (7%) stated they would not have sought additional medical visits if RRT results were available. In the intervention group, 20 families (6.7%) reported that the RRT influenced how their child received care, and 14 families (17%) sought additional care due to RRT results.

Figure. Provider Clinical Decision Making Based on Results of Rapid Respiratory Testing, n = 443

Characteristics of providers and patients by provider decision type

Conclusion

RRT impacts clinical decision making for 1 in 5 ED visits, specifically antiviral prescribing and reduced diagnostic testing. Most families were in favor of RRT, which impacts additional health care visits after the ED encounter.

Disclosures

Suchitra Rao, MD, BioFire (Grant/Research Support) Molly Lamb, PhD, BioFire (Grant/Research Support) Rakesh Mistry, MD, MSCE, BioFire (Grant/Research Support) Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)
691. Results of Repeat HIV-1 DNA Resistance Tests Are Highly Concordant
Authors: Curanovic Dusica , Cai Suqin , Toma Jonathan , Petropoulos Christos J , Walworth Charles M
Published: January 2021

Background

DHHS guidelines recommend caution when interpreting HIV-1 DNA resistance testing because not all previously identified drug resistance mutations (DRMs) may be captured. Comparison of multiple reports from the same patient was performed to assess the ability of HIV-1 DNA testing to consistently identify wild-type and drug resistance alleles.

Methods

Patients with 3 HIV-1 DNA resistance tests (trios) and corresponding HIV-1 viral load (VL) measurements within ~3 months of each resistance test were identified in a commercial database. Concordance among trio test results was assessed for each patient. VL and trio timespan were evaluated for impact on concordance using one-way ANOVA with post-hoc analyses.

Results

Fifty-five patients with test trios were identified for analysis. Average patient age was 53 years, and 88% were male. All 3 tests within 26/55 trios were associated with VL< 200 copies/mL. The average testing timespan was 100 weeks (range 17-228 weeks). Wild-type virus was identified on 3/3 reports for 11/55 (20%) patients. Among resistant viruses, DRMs were identified on average 70%, 20% and 10% on 3/3, 2/3 and 1/3 of HIV-1 DNA reports, respectively. M184V was identified on 3/3, 2/3 and 1/3 reports among 14/17, 2/17, and 1/17 test trios, respectively. K103N was identified on 3/3 and 2/3 reports among 11/12 and 1/12 test trios, respectively. The redetection rate following an initial HIV-1 DNA test was high for M184V (30/34, 88%) and K103N (23/24, 96%).

Of 178 DRMs detected across all initial HIV-1 DNA tests, 17 (9.6%) were not detected on the second, but redetected on the third test, including M184V and K103N in one trio each. The average concordance among test trios across all drug classes was 97%. No correlation between VL at time of testing and DRM redetection rates was observed. Significantly fewer DRMs were recaptured when repeat testing was performed > 24 months after the initial test.

Conclusion

Repeat HIV-1 DNA drug resistance testing reliably detected archived DRMs. DRM decay related to turnover of the viral reservoir may explain some discordance between repeat HIV-1 DNA tests.

Disclosures

Dusica Curanovic, PhD, Monogram Biosciences (Employee) Suqin Cai, n/a, Monogram Biosciences (Employee) Jonathan Toma, n/a, Monogram Biosciences (Employee) Christos J. Petropoulos, PhD, Monogram Biosciences (Employee) Charles M. Walworth, MD, Monogram Biosciences (Employee)
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

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. > 1 mcg/mL) were compared

Results

35.3% of patients had a MIC > 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 >1 mcg/mL, suggestive of prolonged antibiotic therapy. All patients with MRSA-related IE were started empirically on vancomycin. Patients with a MIC > 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 > 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 >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 > 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

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

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 >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

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< 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

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

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 > 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 < .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

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 >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

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 >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 > 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 >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

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 < 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

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)
762. Climate Change and the Seroprevalence of Borrelia burgdorferi over 25 Years in Rhode Island
Authors: Espich Scott , Weinberger Daniel , Mancini Diane , Brancato Janna , Lee Giyoung , Akosa Fredua , Warcup Thomas , Krause Peter J
Published: January 2021

Background

The Ixodes scapularis tick (deer tick or black-legged tick) is the primary vector of Borrelia burgdorferi, the causative agent of Lyme disease. Climatic conditions, specifically temperature, relative humidity, and rainfall, have been shown to affect I. scapularis tick densities. We hypothesized that temperature and moisture correlate with the frequency of human Lyme disease.

Methods

We have carried out a biannual B. burgdorferi serosurvey on Block island, Rhode Island over the past 25 years using a standard B. burgdorferi two-tier ELISA and Western blot assay. Residents of the Island were invited to participate and we only used first visit results. We analyzed B. burgdorferi seroprevalence and weather pattern trends (temperature, rainfall, relative humidity) among a cohort of 2,439 Block Island residents over the past 25 years.

Results

During the months in which ticks are active, we found that both temperature and relative humidity increased on Block Island over the past 25 years (p=0.04 and p=0.03, respectively). We also found that the seroprevalence of B. burgdorferi on the Island increased over the course of the study (p< 0.01), and that increased temperature and moisture in a given season is associated with increased B. burgdorferi seroprevalence in the following season. For example, we found that every inch increase in total rainfall in a given season was associated with a 2% (95% CI 1.01-1.03) increase in the odds of B. burgdorferi seropositivity during the following season. Similarly, we found that every degree Fahrenheit increase in temperature in the spring was associated with a 2% (95% CI 1.02-1.03) increase in the odds of seropositivity in the fall.

Conclusion

We conclude that increasing temperature and moisture are associated with increased frequency of B. burgdorferi infection in humans.

Disclosures

All Authors: No reported disclosures
778. Travel-Acquired Tropical Illness in Children Under the Age of 5: A Scoping Review
Authors: Zaman Michele , Willmott Shannon , Bal Chandandeep , Morris Shaun , Morris Shaun
Published: January 2021

Background

International travel, including by children, is increasing. Due to both biologic and behavioral factors, children face different risks for and disease outcomes in travel acquired illness compared to adults. This systematic literature review aims to identify gaps in knowledge about health outcomes in children under the age of 5 related to international travel.

Methods

We used MEDLINE and Embase databases and followed PRISMA guidelines to conduct a systematic literature review of publications that included extractable information on children under the age of 5 who acquired infectious diseases or other morbidities during international travel. Studies were excluded if they were published prior to 1990, reported on fewer than 5 cases in children under the age of 5, or were letters to the editor. Two independent reviewers completed the abstract screen, full text review and data extraction. In this study, we present results for specific important tropical infections (including malaria and typhoid fever), as well as gastrointestinal, respiratory, and dermatologic illnesses

Systematic Review Flow Diagram

Results

Our literature search (completed on July 17th 2019) identified 8664 citations. 35 citations met our inclusion criteria. Information related to tropical diseases, gastrointestinal, dermatological and respiratory conditions were extracted. Young children, especially those visiting friends and relatives in South Asia and Sub-Saharan Africa are at a higher risk for acquiring tropical infections. Additionally, children in this age group appear to have worse outcomes for conditions such as diarrhea and malaria in comparison to other pediatric age groups.

Tropical Disease Outcomes part 1

Tropical Disease Outcomes part 2

Conclusion

In spite of unique biologic and behavioral traits that may affect risk, outcomes in children under the age of 5 years are rarely presented in the literature distinctly from the overall pediatric population. Future pediatric travel-health research should make efforts to report and analyze data by age in order to better understand the risk for tropical diseases infants face while travelling internationally.

Disclosures

All Authors: No reported disclosures
785. Association between Prevalence of Laboratory-Identified Clostridioides difficile Infections (CDIs) and CDI Antibiotic Treatment in U.S. Acute Care Hospitals, 2018
Authors: Xu Kerui , Benin Andrea L , Wu Hsiu , Edwards Jonathan R , Li Qunna , O’Leary Erin , Leaptrot Denise , Nkwata Allan
Published: January 2021

Background

Clostridioides difficile infections (CDIs) are an urgent public health threat, accounting for 223,900 infections and 12,800 deaths in hospitalized patients annually. In early 2018, the Infectious Disease Society of America (IDSA) recommended oral vancomycin or fidaxomicin as the first-line antibiotics for CDIs. To track the uptake of IDSA’s recommendations, we evaluated the association between CDI prevalence and use of first-line antibiotics in hospitals reporting to the Centers for Disease Control and Prevention’s (CDC’s) National Healthcare Safety Network (NHSN).

Methods

We matched 2018 hospital-level, NHSN data on laboratory-identified CDIs with NHSN antimicrobial use (AU) data for the same time period. Hospitals that submitted < 6 months of either data type in 2018 were excluded. The association between quarterly hospital-level CDI prevalence rates per 100 patient-admissions and use of CDI antibiotics (oral vancomycin plus fidaxomicin) per 1,000 days-present was evaluated using Pearson’s linear correlation coefficient and using Goodman and Kruskal’s gamma (G) on ordinal quartiles to assess rates of discordant pairs.

Results

Among the 2735 hospital-level quarters based on 714 hospitals included in the study, CDI prevalence (median: 0.46 per 100 patient-admissions) and CDI antibiotic use (median: 8.85 antibiotic-days per 1,000 days-present) demonstrated only a moderately positive correlation (r = 0.48). Among hospitals in the highest quartile for CDI prevalence, 5.1% were in the lowest quartile for antibiotic use. Among hospitals in the highest quartile for antibiotic use, 5.3% were in the lowest quartile for CDI prevalence, and 54.2% were in the highest quartile for CDI prevalence (G = 0.60; 95% CI: 0.57–0.63).

Correlation of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in U.S. acute care hospitals, 2018

Distribution of hospital-level Clostridioides difficile infection (CDI) prevalence rates and oral vancomycin and fidaxomicin use in ordinal quartiles (Q1–Q4) to access rates of discordant pairs

Conclusion

The moderate correlation and discordant rates suggest that vancomycin and fidaxomicin are less frequently used as primary antibiotics in some hospitals; whereas in others, CDI antibiotic use is occurring in the absence of positive laboratory tests for CDI. To further investigate this discordance, there is a need to assess hospitals’ prescribing and testing practices in an ongoing manner. These findings may be useful to serve as baseline for measuring progress of appropriateness of treatment and testing for CDIs.

Disclosures

All Authors: No reported disclosures
793. Expert Panel Consensus Ranking of Comorbid Conditions Causally Related to Clostridioides difficile Infection
Authors: Goodman Katherine E , Pineles Lisa , Fridkin Scott , Kyne Lorraine , Loo Vivian , Lora Alfredo J Mena , Perencevich Eli N , Spivak Emily S , Maragakis Lisa , Leekha Surbhi , Harris Anthony
Published: January 2021

Background

Numerous studies have identified comorbidities that are associated with Clostridioides difficile infection (CDI), but current CDC and CMS models for risk adjusting hospital CDI rates do not include patient comorbid conditions. Incorporating patient-level data could improve CDI risk adjustment, but comorbidities would need to be easily electronically available for widescale implementation. Ideally, they would also be causally related to CDI — i.e., true risk factors, not confounders — to facilitate more unbiased inter-hospital comparisons. The current study aimed to determine which comorbid conditions are causally related to CDI based upon expert consensus.

Methods

We used Delphi methodology to administer an iterative, two-round survey with an intervening teleconference, to eight infectious disease experts. Experts evaluated 40 comorbid conditions included in Charlson and Elixhauser comorbidity indices (and thus validated for electronic capture through administrative data), as well as other comorbidities commonly associated with CDI. Experts rated comorbid conditions from 1 (not at all related) to 5 (strongly related), based upon perceived relatedness with CDI. To assign causal relatedness, the following criteria had to be met at the end of round two: 1) majority (> 50%) of experts rating the condition at 3 (somewhat related) or higher; 2) inter-quartile range (IQR) < = 1; and 3) standard deviation (SD) < = 1.

Results

8/40 (20%) comorbid conditions were ranked as causally related to CDI, including patient age, three malignancy comorbidities, two transplant-related comorbidities, HIV/AIDS, and inflammatory bowel disease. A further 18/40 (45%) qualified as indeterminately related, and 14/40 (35%) were ranked as not causally related to CDI (Table). Three of the eight causally related factors were not components of Elixhauser or Charlson indices.

Table

Conclusion

We identified comorbid conditions that may be appropriate candidates to consider for inclusion in patient-level risk adjustment models. Some causal factors did not originate from established comorbidity indices. Thus, future work to validate electronic capture of these conditions could further reduce barriers to risk-adjustment implementation.

Disclosures

All Authors: No reported disclosures
807. Effect of Inter-Hospital Transfer on Nosocomial Infection Rates in Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Marcus Joseph E , Okulicz Jason , Sams Valerie , Batchinsky Andriy , Barsoumian Alice
Published: January 2021

Background

Extracorporeal Oxygenation (ECMO) has been increasingly used as a life support modality for cardiac and pulmonary failure. Due to improved survival in patients treated in high volume ECMO centers, inter-hospital transport of these critically ill patients is on the rise. These patients may be transported via ambulance locally, or by aircraft over long distances. However, potential risks of nosocomial infectious complications associated with transfers has not been reported. We evaluated the impact of transfers on nosocomial infections for patients who received ECMO at Brooke Army Medical Center (BAMC).

Methods

All patients who received ECMO for ≥48 hours at BAMC between May 2012 and October 2019 were included. Chart review was performed to determine transport status, infectious complications while on ECMO, and antimicrobial susceptibility of isolated organisms. Statistical analyses were performed using Chi-squared, Fisher’s exact, or Mann-Whitney U tests as appropriate. Factors associated with nosocomial infections were evaluated by multivariate logistic regression.

Results

Compared to patients who were cannulated locally (n=33), patients who underwent cannulation at referral facility and inter-hospital transfer (n=76) had no difference in infections per 1000 ECMO days (33.1 vs. 30.5, p=0.74) or in infections with multidrug resistant organisms (MDRO) (50% vs. 55%, p=1). Of transferred patients, those transferred by aircraft (n=11) had no difference in infection rate (22.4 vs. 31.8 per 1000 ECMO days, p= 0.39) or MDRO incidence (52% vs 75%, p=0.61) compared to those only transferred by ambulance (n=65). Multivariate analysis showed the greatest risk factor for nosocomial infection was time on ECMO (OR 12.2 for longest tertile time on ECMO vs. shortest tertile, p=0.0001); transport was not significantly associated with infection (OR 2.1, p=0.06).

Nosocomial infection rate by site of ECMO cannulation

Conclusion

This study did not find a significant difference in nosocomial infection rate or recovery of MDROs between transported and non-transported patients on ECMO, regardless of transport modality. This study suggests that transportation is not the primary driver of nosocomial infections in this cohort.

Disclosures

All Authors: No reported disclosures
LB-6. Increased Diagnoses of Acute HIV Infection through Routine ED Screening and Rapid Linkage to Care and initiation of HAART During the COVID-19 Pandemic
Authors: Stanford Kimberly , Schmitt Jessica , Taylor Michelle M , Eller Dylan , Friedman Eleanor , McNulty Moira , Ridway Jessica , Hazra Aniruddha , Michelle Moore , Beavis Kathleen
Published: January 2021

Background

The COVID-19 pandemic has negatively impacted routine HIV screening in healthcare settings. This has serious implications, especially for patients with acute HIV infection (AHI) presenting with symptoms suggesting COVID-19 infection. This is a high priority population for rapid linkage to care (LTC) and initiation of HAART.

Methods

We reviewed data from our eXpanded HIV Testing and LTC (X-TLC) Program, a collaboration effort between 13 healthcare centers on the South and West Sides of Chicago. Since 2016, most sites had 4th or 5th generation HIV Ag/Ab testing available.

Results

Most sites experienced reductions in HIV screens during the COVID-19 pandemic. Advanced planning by our ED incorporated blood draws for HIV screens as part of COVID-19 evaluations. UCM performed 19,111 HIV screens (11,133 in the ED) between 1/1/20 and 8/17/20, along with 100,635 COVID PCRs (14,754 in ED) between 3/17/20 and 8/17/20. Nine patients were diagnosed with AHI after the first case of COVID-19 in Chicago (1/24/20), and 7 were diagnosed after the first case of community transmission in Cook County (3/8/20). All cases of AHI were diagnosed in the ED. The rate of AHI was significantly higher in 2020 versus the prior 4 years (14.4 vs 6.8 per year, p < 0.05). AHI patients comprised 25.7 % (9/35) of all new diagnoses, the highest percent ever. There were 7 men (6 identified as MSM) and 2 cis-gender women, median age of 25 years (21 to 28 years). The median viral load was 6 million (115,000 to > 6 million) copies/mL. Eight of 9 patients presented with an illness indistinguishable from COVID-19, including 1co-infected patient. All were LTC and started on HAART from time of PCR result within a median of 1 day (0–38), but 3 days (range 1–41) from sample collection as a result of delayed reflex PCR confirmatory testing due to high demands on lab personnel and scarcity of reagents due to COVID-19 PCR volumes (since resolved).

HIV Screening and COVID-19 Testing in the ED During COVID-19

Conclusion

Continued HIV screening in our ED during the COVID-19 pandemic identified an increased number of patients with AHI. These individuals may be more likely to present for care due to fear of COVID-19 infection. We achieved rapid LTC and initiation of HAART without any incremental increases in resources. All HIV screening programs should incorporate blood-based HIV screening into their COVID-19 testing programs.

Disclosures

Moira McNulty, MD, MS, Gilead Sciences (Grant/Research Support)
LB-10. Rapid Assessments of Non-Pharmaceutical Intervention Uptake and Population Mobility Patterns Elucidate SARS-Cov-2 Transmission Dynamics
Authors: Wesolowski Amy , Gibson Dustin , Agarwal Smisha , Lambrou Anastasia , Kirk Gregory , Labrique Alain , Mehta Shruti , Solomon Sunil
Published: January 2021

Background

Current mitigation strategies for SARS-CoV-2 rely on population-wide adoption of non-pharmaceutical interventions (NPIs). Monitoring NPI adoption, mobility patterns and their association with SARS-CoV-2 infection can provide key information for public health agencies and be used to calibrate transmission models.

Methods

We used an online panel to accrue representative samples from Florida, Illinois, and Maryland (n=3,009, approximately 1,000 per state) from July 15–31, 2020 and capture socio-demographically and geographically resolved information about NPI adoption and mobility in the prior 2 weeks. Logistic regression was used to identify correlates of self-reported SARS-CoV-2 infection in the prior 2 weeks.

Results

Overall, 96% reported traveling outside their home in the prior 2 weeks, the most common reason being to visit a grocery store/pharmacy (92%), followed by visiting friends/family (61%), and visiting a place of worship (23%); 22% reporting public transportation use. In total, 44% of respondents reported always practicing social distancing and 40% reported always using a mask indoors and outdoors. Overall, 74 (2.5%) reported testing positive for SARS-CoV-2 in the prior 2 weeks, with strong dose-response relationships between several forms of movement frequency and SARS-CoV-2 positivity. Variables capturing mobility were all highly correlated with one another, suggesting there are clusters of individuals who engage in multiple activities (Figure); 41% of positive cases engaged in all forms of mobility captured compared to 1% of those who did not test positive within the prior 2 weeks. Patterns of mobility and NPI uptake did not significantly differ by state; however, there were significant relationships with age, race/ethnicity, and gender. In multivariable models including adjustment for NPIs, significant relationships remained with public transportation, visiting a place of worship, and participating in outdoor group fitness activities.

Figure. Heatmap depicting pairwise Spearman correlation coefficients between survey responses. Pairwise correlation coefficients are displayed in the boxes at intersection of any two variables. Questions were asked with respect activities in the prior 2 weeks.

Conclusion

NPI adoption and mobility did not vary across these three states with variable policies and SARS-CoV-2 positivity rates. Rather, associations with recent positivity appear to be driven largely by mobility patterns and engagement in activities where NPI use may be challenging or inconsistent.

Disclosures

Shruti Mehta, PhD, MPH, Gilead Sciences (Other Financial or Material Support, Speaker) Sunil Solomon, MD, PhD, MPH, Abbott Diagnostics (Grant/Research Support)Gilead Sciences (Grant/Research Support, Advisor or Review Panel member)