bluuebunny/crossref_metadata_2025_split huggingface dataset:
979. Getting Candid with Candida auris: Evaluation of Isolates at SBH Health System
Authors: Willner Debra M , Bisono-Garcia Bismarck , Berger Judith , Berger Judith , Bengualid Victoria , Bathina Parinitha 
Published: December 2021

Abstract

Background
Candida auris is a multidrug resistant yeast that was originally isolated in the external ear of a patient in Japan in 2009. Since then, it has rapidly spread throughout the world. C. auris is inherently a multidrug resistant organism, making echinocandins the drugs of choice. C. auris was first isolated in SBH in a wound culture in 2018, and it has become a major health concern. Our objectives were to evaluate our clinical C. auris isolates, identify potential risk factors for infection, and assess our susceptibilities to determine the most appropriate treatment option.

Methods
This was a retrospective chart review of all clinical isolates of C. auris from July 2018 – April 2021. Data collection included location prior to admission, SBH hospitalization within 90 days, hospital vs community acquired, new vs recurrent, specimen type, susceptibilities, and lines at the time of culture.

Results
A total of 121 clinical isolates were evaluated from 74 patients. Although initially clinical isolates were rare, prevalence increased in subsequent years, with 97 clinical isolates identified in 2020. Isolates were identified in various specimen types, with the majority in urine, respiratory samples, or blood cultures. 64% of the isolates were hospital onset. Among patients who tested positive for C. auris colonization through surveillance testing, 22% proceeded to develop clinical infections. Most of the patients with positive blood cultures had either one or multiple IV access points, which may be a risk factor for candidemia. All isolates were resistant to fluconazole, 87% were susceptible to amphotericin B, and susceptibility to echinocandins ranged from 98-99%.
Susceptibilities

Susceptibilities for the Candida auris clinical isolates received from the NYS Department of Health
Specimen Type

IV Access in Positive Blood Cultures

Access points that were present at the time of candidemia

Conclusion
Candida auris is a persistent fungus that is highly contagious that has been increasing in prevalence. Infection control measures remain the most proven method to decrease the development of clinical infections. Our study has some limitations, such as the retrospective design, the lack of a control group, lack of clinical outcomes, and limited surveillance testing capabilities. C. auris remains a major cause of concern for nosocomial infections, particularly in patients with various indwelling catheters. Our susceptibilities confirmed echinocandins as the class of choice for treatment of C. auris infections.

Disclosures
Judith Berger, MD, Nothing to disclose
118. Machine Learning Approaches to Predicting Treatment Outcomes for Carbapenem-Resistant Enterobacterales in a Region with High Prevalence of Non-Carbapenemase Producers
Authors: Black Cody A , Aguilar Samantha , Bandy Sarah , Gawrys Gerard , Dallas Steven , So Wonhee , Benavides Raymond , Betrabet Neha , Diaz Catherine , Anderson Audrey , Lee Grace 
Published: December 2021

Abstract

Background
Carbapenem-resistant Enterobacterales are a growing threat globally. Early detection of CRE is necessary for appropriate treatment and infection control measures. Many hospital labs can test for carbapenemase production; however, in some regions, including South Texas, the majority of CRE are non-carbapenemase producing (NCPE). This study had two interrelated aims to develop decision rules tailored to a region with high prevalence of NCPE to predict 1) antimicrobial resistance (AMR) from whole genome sequencing (WGS) data and 2) CRE treatment outcomes.

Methods
To better understand links between resistome, phenotypic AMR, and prediction of outcomes for CRE, we developed decision rules to build machine learning prediction models. We conducted WGS and antibiotic susceptibility testing (21 antibiotics) on CRE isolates from unique patients across 5 hospitals in the South Texas region between 2013 and 2020. Day 30 outcomes were based on desirability of outcome ranking (DOOR). The overall classification accuracies of the models are reported.

Results
Overall 146 CRE isolates were included, 97 were used to train each model, and 49 were used for validation. Among the K. pneumoniae and E. coli CRE isolates that were available with susceptibility data, the majority (62%) were NCPE. For the clinical recovery model (DOOR), the combination of admission ICU status, piperacillin-tazobactam (PT) MIC &gt; 16, presence of sul gene, and polymyxin-sparring regimens associated with an overall accuracy of 95% for having a worse DOOR. Majority (60%) of patients were empirically treated with piperacillin-tazobactam; notably, less than 33% isolates had PT MIC ≤ 16. Interestingly, combined effects of isolates that did not harbor carbapenemases, blaOXA-1, blaCTX-M-15, blaCMY, or aac(6’)ib-cr genes resulted in a decision rule with a 95.7% overall accuracy for susceptibility to PT (MIC &lt; 16 ug/mL).

Conclusion
Herein, we used machine learning approaches to predict AMR and treatment-based outcomes linked with WGS data in a region with predominantly NCPE infections. Machine learning can obtain a model that can make repeatable predictions, further data can improve the accuracy and guide tailored clinical decision-making.

Disclosures
Grace Lee, PharmD, PhD, BCPS, Merck Co. (Grant/Research Support)NIA/NIH (Research Grant or Support)
1004. Cladophora in Lake Michigan May Serve as Important Reservoirs for Antibiotic-Resistant Bacteria
Authors: Grayer Dannielle C , Logan Latania K 
Published: December 2021

Abstract

Background
Cladophora is a green algae, native to the Great Lakes, and found in large quantities along Lake Michigan shorelines. Previous studies have shown that Cladophora provide protection and nutrients for the Enterobacteriaceae (Ent) family, allowing persistence and regrowth. Chicago waterways harbor concerning antibiotic-resistant (AR) Ent, however the community reservoirs are unknown. Our primary objective was to assess whether Cladophora harbor AR Ent and to secondarily assess AR Ent in local beach waters where Cladophora are present.

Figure 1. Map of Lake Michigan showing sites (S1-S3) where Cladophora samples were collected. NB, North Beach, Racine, Wisconsin; Michigan City, Indiana; PL, Portage Lakefront, Indiana Dunes National Park, Indiana.

Figure 2. Map of Lake Michigan showing sites (S4-S7) where beach surface water samples were obtained. Montrose, Foster, 63rd St, & Calumet beaches in Chicago, Illinois.

Methods
Cladophora were processed from three Indiana Lake Michigan sites (S1 and S2; Fig 1) in 2002 and 2012 (S3; Fig 1) at the USGS Lake Michigan Ecological Research Station (Chesterton, IN). In 2015, surface water samples were obtained by the USGS at four Chicago beaches (S4-S7; Fig 2), which also amass Cladophora. Bacteria were isolated shortly after collection. In 2019-2020, Ent were cultivated and susceptibilities were performed at Rush.

Results
In 2002-2003 (S1 and S2), 160 E. coli were cultured from Cladophora. There was AR to multiple classes, highest overall in tetracyclines (7.5%, range 6.2%-18.7%), cefoxitin (8%), and cefazolin (5.6%). Resistance to cefuroxime was 0.6%. Four Salmonella isolates from 2012 (S3) were pan-susceptible, while two Citrobacter isolates were resistant to penicillins, 1st and 2nd generation cephalosporins, and cephamycins. Beach surface water samples from 2015 revealed more pronounced AR in E. coli (n=185) involving multiple classes, including highest in ampicillin (12.4%), tetracyclines (8.1%); piperacillin (7%); cefazolin (3.8%), cephamycins (3.2%) and amoxicillin-clavulanate (2.7%). Resistance to 3rd-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole ranged from 0.5-2%. AR Ent varied by beach site with highest percentages at S4, the only site with an associated dog beach.

Conclusion
These findings suggest that Cladophora in recreational waterways may serve as reservoirs for AR Ent. Differences in AR Ent at beach sites may reflect varying degrees of fecal contamination. Identifying community reservoirs is key to better understanding the acquisition of antibiotic resistant Ent among healthy populations and has long-term ecological and public health implications.

Disclosures
All Authors: No reported disclosures
1021. Utility of Cell-Free DNA Sequencing in Diagnosing Murine typhus in Children
Authors: Medina-Carbonell Victoria M , Yespica-Otaola Enrique A , Beatty Kim , Fergie Jaime 
Published: December 2021

Abstract

Background
Murine typhus is a zoonotic infection caused by Rickettsia typhi and transmitted through infected fleas. Geographic distribution within the United States is limited primarily to South Texas and Southern California. Infection is typically associated with a triad of fever, headache, and rash, although is only present in one-third of cases. Immunofluorescence assay (IFA) is currently the gold standard for diagnosis, but it has its limitations as it is dependent on the time to seroconversion and has low specificity due to cross-reactivity among other rickettsial species. Cell-free DNA (cfDNA) sequencing for broad-range pathogen detection may offer higher sensitivity at the early stages of the disease.

Methods
We performed a retrospective electronic medical record search of children with cfDNA sequencing detection of Murine typhus hospitalized at Driscoll Children’s Hospital, Corpus Christi, Texas, between June 2020 and May 2021.

Results
We found 4 children (range 9-15 year-old) positive for R. typhi by cfDNA sequencing. All patients presented with fever of unknown origin and rash. Also, 2 patients were diagnosed with pneumonia. One patient exhibited severe illness with acute kidney injury, elevation of transaminases and encephalitis that warranted admission to the pediatric intensive care unit. All patients defervesced and improved within 48 hours of doxycycline initiation; average length of stay 6 days (range 3-12 days). In one patient, M. typhus was detected by Karius® test only, in the other three was concordant with serology.

Conclusion
We highlight next-generation cfDNA sequencing as a useful tool in identifying the etiologic agent of patients with fever of known origin, where murine typhus is one of the possible etiologies. Preventing extensive laboratory workup and subsequent delay of assessment and management. The rapid turnaround time of cfDNA test allows for de-escalation of therapy and initiation of appropriate treatment.

Disclosures
Jaime Fergie, MD, AstraZeneca (Scientific Research Study Investigator)Explify (Speaker’s Bureau)Karius (Speaker’s Bureau)Pfizer, Merck, AstraZeneca, and Sanofi (Speaker’s Bureau)Pfizer, Merck, Sanofi, and Moderna (Consultant, Advisor or Review Panel member)
1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
Authors: Degner Nicholas R , Galvan-Castillo Ricardo , Alexander Jose , Arun Aparna , de Vries Christiaan R , Macintyre Ann , Perkins Bradley , Ahmed Asim A , Smollin Matthew 
Published: December 2021

Abstract

Background
Capnocytophaga canimorsus (Cc) and Pasteurella multocida (Pm) are gram negative bacterial commensal pathogens typically from dogs or cats that can cause severe infection in humans when spread through licks, scratches or bites. The diagnosis of these infections can be limited by: (1) their fastidious nature and difficulty to culture; (2) the nonspecific manifestations of the infections; and (3) the unreliability of dog or cat exposure history. Open-ended microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations.

Methods
The Karius TestTM (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of &gt; 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Cc and Pm were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting.

Results
KT detected 5 cases of Cc (25,039 MPM +/- 41,062) and 8 cases of Pm (33,264 MPM +/- 69,301) (Table 1). All detections of Cc were in adults (60% male) and included 2 cases of culture-negative endocarditis (one with known liver disease) and one case of sepsis with diffuse rash. Pm detections occurred in 6 adults and 2 children (75% male) and included 2 cases of culture-negative endocarditis, and single cases each of endovascular graft infection, pneumonia, fever of unknown origin, and a cranial dog bite complicated by an abscess. Two patients had immunocompromising conditions including neuroblastoma and aplastic anemia.

Conclusion
Unbiased, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical infections by Cc and Pm. These cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with non-specific clinical manifestations and broad differential diagnoses.

Disclosures
Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Galvan-Castillo, MD, Karius Inc. (Employee, Shareholder) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)
1034. FebriDx use in Immunocompromised Patients in a Real-World Hospital Setting during the second (COVID-19) wave in Italy
Authors: Lagi Filippo , Bartoloni Alessandro , Suarez-Cuervo Catalina 
Published: December 2021

Abstract

Background
The diagnosis of acute respiratory infection (ARI) in patients with immunosuppression secondary to disease or medications is often unclear. Symptoms may be absent or blunted, and acute phase reactants, like procalcitonin (PCT) and C-reactive protein (CRP) may not elevate. For these patients, minor signs or symptoms could lead to hospitalization and antibiotic prescriptions to prevent complications or death. FebriDx® is a rapid, qualitative immunoassay test designed to distinguish between viral or bacterial respiratory infection through simultaneous detection of both CRP and Myxovirus resistance protein A (MxA) from a fingerstick blood sample.

Methods
FebriDx was evaluated as part of a real-world prospective, observational study in hospitalized patients with symptoms of ARI and suspected COVID-19 in a single tertiary care center in Italy (August, 2020 - January, 2021). A sub analysis of patients with expected reduced host immune responses secondary to immunosuppression by disease or medication was performed. (Classified by treating clinician; patient on high dose steroids/ immunosuppressive therapy, or underlying condition like cancer or autoimmune disease). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios were calculated for FebriDx with respect to the final diagnosis.

Results
We included 28 patients from 200 in the study, 16 patients had a final diagnosis of bacterial infection and 12 had viral infection. FebriDx showed a sensitivity of 91.7% to accurately diagnose viral infection and 93.8% for bacterial infection (see tables). Serum CRP was not available for 4 of the patients included (14%) and elevated in the remaining patients. PCT was not available for one patient with viral infection and was elevated in 50.0%.

FebriDx Performance when compared to Clinical Diagnosis

Conclusion
FebriDx demonstrated a higher accuracy for differentiating bacterial vs. viral infection in an immunocompromised cohort than single biomarkers CRP and PCT. FebriDx demonstrated a high diagnostic accuracy to differentiate viral from bacterial infection in patients with chronic immunosuppressive conditions in a real-world setting and had better performance than standalone CRP and PCT to distinguish viral and bacterial ARI in immunocompromised patients.

Disclosures
Catalina Suarez-Cuervo, MD, Lumos Diagnostics (Employee)
1056. Safety and Tolerability of Dalbavancin in Vancomycin Allergic Patients – A Case Series
Authors: Freeman Kennedy J , Cleveland Kerry O , Bland Christopher M , Jones Bruce M 
Published: December 2021

Abstract

Background
VVancomycin and dalbavancin, both in the glycopeptide class of antibiotics, are used in the treatment of Gram-positive infections, including methicillin-resistant Staphylococcus aureus. Antibiotics in this class contain a heptapeptide core that has potential for cross-sensitivity. Due to this risk, dalbavancin carries a warning in the package insert for use in patients with a glycopeptide allergy. Dalbavancin, a semi-synthetic derivative of vancomycin, has lipophilic side chains which reduce the risk of cross-sensitivity to vancomycin. This case series evaluated patients with a listed vancomycin allergy in their electronic health record who received dalbavancin as an outpatient infusion.

Methods
This study was a non-randomized, retrospective chart review of adult patients who had a documented vancomycin allergy and received dalbavancin between February 2016 and February 2021 for any indication in the outpatient setting. The primary objective was to evaluate dalbavancin tolerability in patients allergic to vancomycin. Patient characteristics and the specifics of dalbavancin infusion – dose, volume, infusion rate, intravenous line access, and receipt of premedication before infusion – were collected on each patient.

Results
559 unique patients received dalbavancin over the time frame. Of these, ten had a documented, subjective vancomycin allergy. Patient-reported allergic reactions were rash (4), hives (3), anaphylaxis (2), red man syndrome (2), renal failure (2), and general malaise (1). Six patients had at least 1 additional subjective drug allergy. The various infections treated included cellulitis/abscess (8), osteomyelitis (1), and bacteremia (2). Most patients received 1500mg (2 received 1125mg) of dalbavancin in 300-500mL of dextrose 5% in water infused at either 600 or 1000mL/hr via a peripheral (6) or central (4) intravenous line. All patients tolerated the infusion with no adverse events reported and no receipt of premedication before administration.

Conclusion
Dalbavancin may be a reasonable treatment option in vancomycin allergic patients, despite possible cross-sensitivity. Further investigation into cross-sensitivity between vancomycin, dalbavancin, and other glycopeptide class agents is warranted.

Disclosures
Kerry O. Cleveland, M.D., AbbVie (Speaker’s Bureau)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau)
1071. Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis (IE) Due to Methicillin-Resistant Staphylococcus aureus (MRSA)
Authors: Huang David , Gaukel Eric , Borroto-Esoda Katyna , Xiong Yan , Abdelhady Wessam , Bayer Arnold 
Published: December 2021

Abstract

Background
Anti-staphylococcal phage lysins, such as LSVT-1701, represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We, thus, sought to examine the in vivo efficacy of LSVT-1701 combination with daptomycin, a standard-of-care anti-MRSA agent with proven efficacy against bacteremia and IE in humans.

Methods
We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of LSVT-1701 plus daptomycin. We examined microbiologic outcomes in distinct target tissues (cardiac vegetations, spleen and kidney) in this model, as well as the pharmacokinetic and pharmacodynamic drivers and target attainment values most predictive of treatment outcomes. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was administered in combination with daptomycin at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes.

Results
The Table below shows all LSVT-1701 regimens in combination with daptomycin significantly reduced MRSA burdens in all target tissue as compared to untreated controls. The reduction in MRSA counts was statistically significant in instances of both increasing LSVT-1701 dose level (i.e., single doses of 50 mg/kg vs 32.5 mg/kg iv), as well as increased numbers of lysin doses (i.e., four daily doses vs a single-dose or two daily-doses) in combination with daptomycin. Of note, both the LSVT-1701 50 mg/kg and 32.5 mg/kg daily dose-strategies given for four days in combination with daptomycin sterilized all target tissues (i.e., quantitative cultures ≤ the lower limit of detection of 1 log10 CFU/g. tissue).

MRSA bio-burdens in blood, vegetations, kidneys and spleen in rabbit IE model

Conclusion
LSVT-1701 administered at 32.5 or 50 mg/kg in a 4 d daily-dose regimen in combination with daptomycin resulted in microbiologic sterilization of all target organs in this MRSA IE model. These data support further clinical development of LSVT-1701 for the treatment of MRSA endovascular infections including IE.

Disclosures
David Huang, MD, PhD, Lysovant (Consultant) Eric Gaukel, BS, Lysovant (Employee) Katyna Borroto-Esoda, PhD, Lysovant (Consultant) Arnold Bayer, MD, PhD, Lysovant (Grant/Research Support)