bluuebunny/crossref_metadata_2025_split huggingface dataset:
1204. The Effect of Coinfection with Babesiosis and Lyme Disease on Novel Biomarkers
Authors: Lum Michael D , Reardon Kelsey , Spector Rachel , Garry Evan , Papamanoli Aikaterini , Marcos Luis 
Published: January 2021

Abstract

Background
Current literature presents conflicting results regarding the clinical manifestations of coinfection with Babesia microti (Babesiosis) and Borrelia burgdorferi (Lyme disease). The aim of this study is to investigate the effect that coinfection with Babesiosis and Lyme Disease has on standard and novel biomarkers markers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and procalcitonin (Pc), which may assist in elucidating how these pathogens interact within human hosts.

Methods
Babesia cases were collected from Stony Brook University Hospital from 2012 to 2019. Cases of Babesia were included if parasites were detected by peripheral blood smear and confirmed by PCR. Lyme disease diagnosis criteria involved 2-tier testing per CDC guidelines. Cases were divided into three cohorts based on if they had CRP, ESR or Pc tested. Cohorts were divided into two groups: Babesiosis alone vs coinfection with Lyme Disease. Median values were analyzed for the following biomarkers across both groups: parasitemia, hemoglobin (Hgb), white blood cells (WBC), platelets, indirect bilirubin (IB), lactate dehydrogenase, ESR, CRP and Pc. Fisher Exact and Wilcoxon Rank sum tests were used and P values &lt; 0.05 were considered statistically significant.

Results
ESR values trended higher in monoinfection compared to coinfection (50 vs 36 mm/hr, p=0.63). Within this cohort, the coinfection group had significantly lower platelet values compared to monoinfection (52 vs. 75.5 K/uL, p=0.04, Table 1). Within the CRP and Pc cohorts, monoinfection had higher trends of parasitemia compared to coinfection (CRP group: 1.6 vs 0.7%, p=0.14, Pc group: 1.4 vs 0.7% p=1.0, Table 2&3). Pc levels were similar in both groups (1.1 vs 1.2 ng/mL, p=1.0, Table 3).
Table 1: Demographics and Biomarkers for Patients with Babesiosis Monoinfection vs. Coinfection with Babesiosis and Lyme Disease that had ESR Measured.

Table 2: Demographics and Biomarkers for Patients with Babesiosis Monoinfection vs. Coinfection with Babesiosis and Lyme Disease that had CRP Measured.

Table 3: Demographics and Biomarkers for Patients with Babesiosis Alone vs Coinfection with Babesiosis and Lyme Disease that had Procalcitonin Measured.

Conclusion
Coinfection had significantly lower platelets within the ESR cohort but not in other cohorts. While not statistically significant, monoinfection showed greater trends of ESR and parasitemia, which is consistent with previous studies that suggest that
B. burgdorferi may mitigate the effects of B. microti infection. CRP and Pc levels were similar across both groups suggesting that the utility of using novel biomarkers to elucidate the interaction between B. burgdorferi and B. microti during simultaneous infection requires further study.

Disclosures
All Authors: No reported disclosures
94. Appropriate Urine Legionella Antigen Testing: A Step Towards Diagnostic Stewardship
Authors: Ahmad Faran , Ahmed Moeed , Velagapudi Manasa , Bittner Marvin J 
Published: January 2021

Abstract

Background
Pneumonia is a leading cause of sepsis and hospitalization. Infectious Diseases Society of America and American Thoracic Society (IDSA/ATS) published 2019 practice guidelines for community-acquired pneumonia (CAP), recommending urinary antigen testing (UAT) for Legionella pneumophila (LP) only in patients with severe pneumonia or having epidemiological risk factors. In the last 20 years, there has been no Legionella outbreak in Nebraska. Currently, the urine antigen test is considered based on the discretion of the ordering provider. However, this usually results in over-utilization of the test and associated financial burden.

Methods
Retrospective chart review of patients admitted to Bergan Mercy Medical Center, Creighton University, Omaha with the admission diagnosis of community-acquired pneumonia in the year 2019, by using electronic medical records. The charts were reviewed for baseline characteristics, admission diagnoses, and clinical outcomes. The project was submitted to and reviewed by the institutional review board.

Results
From January to December 2019, 4738 patients were admitted to the general medical floors with the diagnosis of community-acquired pneumonia. Among those patients, 826 patients (17.43%) had urine Legionella antigen tests done, only 11 (0.23%) were tested positive. Moreover, 140 patients (2.95%) had urine Legionella antigen tests in the absence of a documented diagnosis of community-acquired pneumonia. Patients admitted to intensive care units were not included in the study as guidelines do not restrict from ordering urine Legionella tests in patients with severe sepsis secondary to community-acquired pneumonia.

Conclusion
A diagnostic stewardship approach should be considered for urine Legionella antigen testing. Moreover, such a retrospective review provides an opportunity for quality improvement initiatives at the academic medical facilities with lower Legionella outbreaks.

Disclosures
All Authors: No reported disclosures
1208. Development of a Novel Synthetic Glycan to Prevent Bacterial Infections and Ameliorate Respiratory Viral Infections
Authors: Meisner Jeffrey , Lee Jackson , Lawrence Jonathan , Roed Megan , Vlieg Johan van Hylckama 
Published: January 2021

Abstract

Background
The prevention and treatment of bacterial infections is a human health challenge. A disadvantage of antibiotics is that they often kill beneficial commensal, bacteria in addition to, pathogenic bacteria. Indiscriminate killing disrupts the homeostasis between commensal bacteria and the host gut epithelium allowing colonization of the gut by pathogenic bacteria and increases susceptibility to infections. This research was done to develop a non-antibiotic modality to prevent bacterial infections by growing, rather than killing, commensal bacteria in the gut. Gut commensal bacteria grown on carbohydrates produce short-chain fatty acids (SCFAs) that support gut homeostasis maintenance and promote resistance to bacterial colonization. SCFAs have direct and indirect effects on the gut and lung mucosal immune system. They have also been linked to respiratory viral infection reduction and shown to influence macrophage function to mitigate pro-inflammatory neutrophil-mediated tissue damage.

Methods
A library of over 1,500 synthetic proprietary glycans, termed Microbiome Metabolic Therapies (MMT™), was synthesized using different chemical and enzymatic approaches. An ex vivo platform using fecal bacterial communities from human subjects was devised to screen MMTs for their abilities to deplete pathogenic bacteria, and modulate multiple aspects of bacterial metabolism.

Results
KB109 was identified based on its ability to reduce the relative abundance of a diversity of pathogens including clinically relevant Gram-negative and Gram-positive bacteria in human fecal communities. KB109 also increased the relative abundance of prevalent commensal bacteria. Monoculture experiments demonstrated that KB109 promotes the growth of commensal bacteria, but not pathogens. Ex vivo screening revealed that KB109 consistently increased SFCA production across multiple fecal communities.

Conclusion
KB109 represents an appealing activity profile and offers an opportunity to prevent enteric and systemic bacterial infections by promoting gut homeostasis and colonization resistance, and ameliorating respiratory viral infections by stimulating immune homeostasis. KB109 is under evaluation in two COVID-19 clinical studies.

Disclosures
Jeffrey Meisner, PhD, Kaleido Biosciences (Employee, Shareholder) Jackson Lee, PhD, Kaleido Biosciences (Employee, Shareholder) Jonathan Lawrence, PhD, Kaleido Biosciences (Employee, Shareholder) Megan Roed, BA, Kaleido Biosciences (Employee, Shareholder) Johan van Hylckama Vlieg, PhD, Kaleido Biosciences (Employee, Shareholder)
1210. K-mer Profiling Powered by Reference-assisted Assembly of NGS Data: A Highly Sensitive Protocol to Infer the Plasma Microbiome Using Cell-free DNA Sequence Data
Authors: Sinha Rohita , Kleiboeker Steve , Altrich Michelle , Bixler Ellis 
Published: January 2021

Abstract

Background
Cell-free DNA (cfDNA) has emerged as an important clinical specimen to probe for pathogenic microbes, especially in organ transplant patients where the same data can be used to predict allograft rejection. Recent reports described viral, bacterial or the complete microbial diversity in plasma following cfDNA sequencing. The prevalence of certain viral families (anelloviridae) is associated with immunosuppressant dosage and the risk of antibody mediated rejection. While being informative, the cfDNA reads are inherently shorter in length (~160bp or 2x75bp) and predominated by the host DNA (~97-99%), causing challenges in their taxonomic annotation and lower specificity. Here we present a computational protocol which minimizes these challenges by merging the concept of “Reference-assisted Assembly” with K-mer profiles of NGS data, for highly sensitive and specific microbial detection.

Methods
We developed a pipeline in which non-host NGS data (reads not mapped to the human genome) undergo a reference-assisted assembly operation and then taxonomic annotation using KrakenUneq (a K-mer based classifier). We trained the KrakenUneq on an in-house and curated database of ~12,000 viral genomes. We used three different K-mer values (16, 21, 31) to train KrakenUneq, and final predictions are made by applying a majority-wins rule. Currently the default KrakenUneq database is used for bacterial & fungal metagenome analysis. We tested our method on 30 simulated and 124 clinical samples obtained from a biorepository.

Results
Our protocol currently screens for a targeted list of pathogens (15 viral species, 16 bacterial and 10 fungal genera). On a simulated set of viral sample mixes, our protocol had 100% accuracy. For 124 clinical samples, predictions were evaluated for specificity and sensitivity using qPCR assays for the following viral species: EBV, BKV, JCV, HSV1/2, HHV7, and CMV. Total 33/38 computational predictions (87%) were confirmed by qPCR. The prediction sensitivity in terms of cps/ml ranged from 6 - 106 copies/mL.

Conclusion
Our efforts to perform ‘Reference-assisted assembly’ followed by K-mer based taxonomic annotation of cfDNA data, led to development of a novel and accurate pathogen detection protocol.

Disclosures
Rohita Sinha, PhD, Viracor-Eurofins (Employee) Steve Kleiboeker, DVM, PhD, Viracor-Eurofins (Employee) Michelle Altrich, PhD, Viracor-Eurofins (Employee) Ellis Bixler, MS, Viracor-Eurofins (Employee)
1211. Response to Fecal Microbiota Transplant (FMT) in Refractory Clostridioides difficile Infection (CDI) is Modest Compared to Recurrent CDI in Hospitalized Patients
Authors: Shin Jae Hyun , Hays R Ann , Warren Cirle 
Published: January 2021

Abstract

Background
There are limited options for Clostridioides difficile infection (CDI) refractory to conventional antibiotic therapy (metronidazole, vancomycin, or fidaxomicin). Fecal microbiota transplant (FMT) is considered a safe and effective treatment for recurrent CDI but has not been widely utilized for refractory CDI due to concerns about safety. Even when included in studies, refractory CDI has not been analyzed separately from recurrent CDI. We reviewed cases of FMT performed in the inpatient setting for CDI to evaluate its safety and efficacy for refractory CDI.

Methods
Patients who received FMT inpatient at University of Virginia Health System for recurrent or refractory CDI after Infectious Diseases and Gastroenterology consultation signed informed consent acknowledging that FMT was considered investigational use in CDI not responding to standard of care as per 2014 FDA guidance. Charts were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting.

Results
Starting in July 2014, 13 patients received FMT for CDI as inpatients. Six received FMT for recurrent CDI, with four having complete resolution, one had recurrent CDI, and one had persistent C. difficile-negative diarrhea, for cure rate of 83%, comparable to published studies. Seven patients received FMT for refractory CDI, with three resulting in complete resolution. One responded to FMT but refused further care, one died from multiorgan failure after initial response to FMT that was possibly related to CDI, strongyloides, and/or CMV. Two patients had ongoing diarrhea suggestive of post-infectious irritable bowel syndrome, one was C. difficile-negative and one was not tested. The cure rate was 57%, lower than that of the recurrent CDI, but without any clear evidence of microbiologic failure.
Outcome of patients undergoing FMT for CDI in the inpatient setting at University of Virginia Health System

Conclusion
Cure rate for FMT for refractory CDI was lower than recurrent CDI, but review of the cases of treatment failures did not reveal any microbiologic evidence of failure. FMT should be considered an alternative option when treating refractory CDI.

Disclosures
All Authors: No reported disclosures
1212. Temporal Dynamics of the Plasma Microbiome in Recipients at Early Post-liver Transplantation
Authors: Okumura Toshihiko , Horiba Kazuhiro , Kamei Hideya , Takeuchi Suguru , Suzuki Takako , Torii Yuka , Kawada Jun-ichi , Takahashi Yoshiyuki , Ogura Yasuhiro , Ogi Tomoo , Ito Yoshinori 
Published: January 2021

Abstract

Background
Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection, but poses a risk for severe infectious diseases. Antimicrobials are often required for patients after LT. Recently, the genomes of multiple microorganisms have been detected in blood, which is essentially sterile. Immune modulation and antimicrobials affect the blood microbiome. Thus, determining the impact of immunosuppression and antimicrobials on the microbiome may be important to understand immunocompetence, predict clinical adverse events after LT such as acute cellular rejection (ACR), and treat infectious diseases.

Methods
Fifty-one patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected within a week after LT, 4±1 weeks after LT, 8±1 weeks after LT, and within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS). Sequence data were imported into the custom-made analysis pipeline PATHDET.

Results
The relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period (figure 1). Microbiome diversity was higher within a week after LT than at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly decreased (figure 2) and the plasma microbiome diversity was significantly higher in patients with ACR than in non-ACR patients. Finally, sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples (figure 3), and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe infectious diseases.
Change in the relative abundance of each microorganism at the family level of taxonomic hierarchy in plasma samples after liver transplantation

Comparison of the plasma microbiome at the family level in patients with and without acute cellular rejection

Relative abundance of microorganisms at the species level in plasma from patients with positive blood cultures

Conclusion
The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients.

Disclosures
All Authors: No reported disclosures
1214. Clinical characteristics of patients with adrenal insufficiency presenting fever
Authors: Jang wooyoung , Sohn Youngseok , Park Jung Hwan , Kim Bongyoung 
Published: January 2021

Abstract

Background
The aim of the present study is to analyze the clinical characteristics of adrenal insufficiency patients presenting fever.

Methods
A single-center retrospective study was conducted in an 846-bed tertiary hospital in South Korea. All hospitalized adult patients (age ≥19 years) who diagnosed with adrenal insufficiency between March 1, 2018 and June 30, 2019 were recruited. Only the first event per patient was included and patients were excluded if they: (1) had proven structural problems with adrenal or pituitary gland, (2) had a history of chemotherapy within 6 months prior to the diagnosis of adrenal insufficiency, and (3) had other medical conditions which may cause fever.

Results
A total of 150 cases were included: 45 (30.0%) had fever and 105 (70.0%) did not have fever at the time of diagnosis of adrenal insufficiency. The proportion of female patients was lower in patients with fever compared to those without fever (44.4% vs. 67.6%, P =0.008). In addition, patients with fever were diagnosed at 13.98 ± 14.51 days, which was later than 6.47 ± 6.91 of patients without fever (P &lt; 0.001). Higher proportion of patients with fever had history of surgical procedure within 6 months (33.3% vs. 11.4%, P =0.001) and antibiotic usage at the time of diagnosis (80.0% vs. 17.1%, P &lt; 0.001) compared to those without fever. Among clinical manifestations, general weakness (91.1% vs. 66.7%, P =0.002), headache (15.6% vs. 4.8%, P =0.044), and cough (17.8% vs. 4.8%, P = 0.022) were more frequently observed in patients with fever. There were no significant differences in clinical outcomes between two groups. According to the multivariate analysis, female sex (OR =0.32, 95% CI: 0.12–0.86, P = 0.024) lowered the risk for adrenal insufficiency with fever. In comparison, history of surgical procedure within 6 months (OR = 4.35, 95% CI: 1.23–15.39, P =0.023), general weakness (OR = 7.21, 95% CI: 1.71–30.37, P =0.007), and cough (OR = 17.29, 95% CI: 1.09–274.92, P =0.043) were significantly associated with adrenal insufficiency with fever.
Table. Risk factors for adrenal insufficiency with fever using a multivariable logistic regression model

Conclusion
Approximately 30% of adrenal insufficiency presented fever. In patients with adrenal insufficiency and male sex, history of surgical procedure within 6 months, general weakness, and cough may be associated with presenting fever.

Disclosures
All Authors: No reported disclosures
95. Assess reasons for continuing antibiotics in persons with positive respiratory viruses PCR in the emergency room
Authors: kassar rawan , dandukuri nandini , troquet jean- Marc , Frenette Charles 
Published: January 2021

Abstract

Background
Respiratory tract infections remain one of the major reasons for inappropriate antibiotic usage. The multiplex PCR respiratory viral panel improves the diagnostic ability of viral causes of RTI and have been advocated as a useful stewardship tool. We sought to evaluate factors leading to continued antibiotic following a positive respiratory viral PCR and to evaluate the impact of a targeted antimicrobial stewardship intervention on antibiotic use.

Methods
In this Quasi experimental study, adult patients presenting to RVH ER with positive respiratory PCR from January 13 2020 to February 27 2020 were reviewed. Patient demographics, clinical, comorbidities, laboratory and radiology reports, antibiotic and antiviral usage before and after test were recorded. For patients without microbiological or radiological evidence of bacterial infection, a standard questionnaire was administered to treating physician. Antibiotic prescribing rate before and following a positive PCR and antibiotic discontinuation following ASP questionnaire was tracked.

Results
During the study period, 147 adult patients presented to the ER with positive respiratory PCR were. Among the study population, antibiotic prescription rate was 49% prior to test result. Influenza was the most common respiratory virus isolated(89/147). Following the respiratory viral PCR, antibiotics were stopped 39% and continued in 51 % by the treating physician. Main reasons for antibiotic continuation included concurrent bacterial infection16/30 (pneumonia 9/30), COPD exacerbation 5/30, febrile neutropenia (5/30) and hemodynamic instability(4/30). Antibiotics were continued without obvious indications in 15 patients and were targeted for intervention. Overall 66% (10/15) of ASP interventions were accepted and antibiotics discontinued. Overall antibiotics were discontinued in 53 % of patients in whom they were initiated pretest result.

Conclusion
This study shows that positive respiratory virus PCR is very useful as it led to discontinuation of antibiotics by treating physician in 40 % and further 13% by an antibiotic stewardship intervention. Adding a stewardship intervention after test result further adds reduction to antibiotic usage.

Disclosures
All Authors: No reported disclosures
1215. Evaluation of the Carba-R NxG Assay in a Global Challenge Set of Pseudomonas aeruginosa
Authors: Gill Christian M , Asempa Tomefa E , Tickler Isabella A , Cruz Caitlin dela , Tenover Fred C , Nicolau David P 
Published: January 2021

Abstract

Background
Carbapenem-resistant P. aeruginosa (CRPA) is a growing clinical challenge. Carbapenemase production is particularly problematic due to high transmissibility and limited treatment options. Carbapenemase prevalence and diversity are largely driven by geography and thus testing spectrum will dictate utility in certain regions. The purpose of this study was to evaluate the performance of the research-use-only Xpert® Carba-R NxG (Carba-R NxG) and commercially available Xpert® Carba-R (Carba-R) in a global collection of P. aeruginosa.

Methods
The challenge set included 123 clinical P. aeruginosa isolates from 11 countries. Isolates were previously categorized via PCR or whole-genome sequencing. Carbapenemase classes tested include: VIM, IMP, NDM, SPM, KPC, and GES. Non-carbapenemase (non-CP) harboring isolates were also tested (negative control). Isolates were tested using the Carba-R NxG and the Carba-R per manufacturer instructions. Carba-R NxG testing was completed by Cepheid (Sunnyvale, CA) blinded to genotype. Test performances were tabulated for each assay by carbapenemase class.

Results
Both assays gave negative results for all non-CP isolates and positive results for all VIM, NDM, and KPC isolates. An improvement in IMP detection among isolates was observed (Carba-R NxG 100% vs. Carba-R 58% detection). All SPM and GES isolates, targets not present in the current Carba-R, were positive by Carba-R NxG. Two isolates harbored both VIM and GES, while a third isolate contained VIM and NDM. The Carba-R NxG identified both targets in all 3 isolates while the Carba-R was negative for both GES-containing isolates. Table 1 provides the test performance of both assays. Overall, the Carba-R NxG successfully categorized 100% of isolates tested compared with 68% for its predecessor.
Table 1. Test performance of Carba-R NxG and Commercially Available Carba-R by Carbapenemase Class.

Conclusion
As the prevalence and diversity of carbapenemase-producing CRPA continues to expand, the Carba-R offers a rapid and sensitive assay to identify clinically relevant carbapenemase genotypes to inform infection prevention and therapeutic interventions. The Carba-R NxG will expand the current targets including SPM, GES, NMC/IMI, and IMP-subtypes, outside the previous testing spectrum, increasing the global utility of the test.

Disclosures
Isabella A. Tickler, BS, Cepheid (Employee) Caitlin dela Cruz, BS, Cepheid (Employee) Fred C. Tenover, PhD, Cepheid (Employee) David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support)