bluuebunny/crossref_metadata_2025 huggingface dataset:
114. Prospective Trial of Passive Diversion Device to Reduce Blood Culture Contamination
Authors: Arnaout Sami , Ellison Richard T , Greenough Thomas C , Wedig Azalea , Mitchell Michael J , John Lauren St , Stock Shannon
Published: December 2021

Background

Blood culture contaminants can lead to inappropriate antibiotic use, prolonged length of stay, and additional hospital costs. Several devices have been developed to reduce the risk of blood culture contamination by diverting a portion of the initial blood sample from the blood culture bottle. We have assessed the effectiveness of one blood diversion device in a prospective trial performed at the two separate emergency departments (EDs) of a three-campus Academic Medical Center.

Methods

A multi-phase prospective crossover trial was performed with the blood diversion device initially in use at one ED (Memorial) and standard equipment at the other ED (University) for 10 weeks. After a washout phase, a second 10-week study phase used the blood diversion device in the other ED (University) and standard equipment at the first ED (Memorial). Contaminants were identified by the clinical microbiology lab using standard criteria, and further defined by independent retrospective review by 3 infectious disease physicians prior to statistical analysis. An intention-to-treat analysis was performed, and Chi-square tests were used to compare contaminant rates among samples obtained using the blood diversion device versus standard equipment.

Results

5,675 blood samples were obtained with 5,661 samples analyzed after 14 were deemed inconclusive by the ID physician review. There were 1,719 samples obtained at Memorial ED and 3,942 at University ED, with 2,836 samples collected during diversion device periods and 2,825 during standard equipment periods. Based on the ID physician review, the contaminant rates were 1.9% in diversion device periods versus 2.9% in standard equipment periods (P = 0.018). There was a marked difference in blood culture contamination rates between the two EDs with contaminant rates at the Memorial ED of 1.1% and 1.4% (P=0.57), and at the University ED of 2.3% and 3.5% (P=0.024) for the diversion device and standard equipment periods, respectively.

Conclusion

The blood diversion device was able to significantly lower blood culture contamination rates overall by 1% at the institution’s two EDs (34% relative reduction), with a stronger effect noted at the campus with both a level 1 trauma center and transplant programs.

Disclosures

All Authors: No reported disclosures
948. Ventricular Assist Device Infection due to Non-tuberculous Mycobacteria Leading to Successful Heart Transplantation: A Case Report and Literature Review
Authors: Saldana Carlos s , Rehm Susan J , Rehm Susan J , Koval Christine E , Unai Shinya , Tong Zhen-Yu (Michael)
Published: December 2021

Background

A 59-year-old man with acute myelogenous leukemia and matched allogeneic hematopoietic stem-cell transplant and non-ischemic cardiomyopathy requiring a left ventricular assist device (LVAD; HeartMate II™) was admitted after the spontaneous rupture of an abdominal fistula in his lower abdomen, and cloudy discharge from the driveline (DL) exit site for months. Figure 1 Denied systemic symptoms but had leukocytosis. CT scan of the abdomen revealed soft tissue enhancement around the LVAD DL Figure 2. Cultures from DL discharge grew Mycobacterium chelonae. He underwent incision and drainage (I&D) of the abdominal fistula, with unroofing of the tissue over the DL. Antimicrobial course is summarized in Table. He was thought to be an appropriate heart transplant candidate one month later. Cultures from the LVAD sites were negative. He completed antimicrobials for 10 weeks after transplant. 32 months after heart transplant he has no signs of M. chelonae infection.

Figure 1. Driveline exit site with scant cloudy discharge and a shallow 3 x 2-centimeter open lesion inferior to the umbilicus. Driveline track in dotted line.

Figure 2. CT scan of the abdomen revealed soft tissue enhancement (red arrows) around the LVAD driveline in the lower abdomen.

Methods

We performed a literature review of all published cases involving Non-Tuberculous Mycobacteria (NTM) and LVADs. Collected: date, sex and age, onset, organism, type of LVAD, transplant, surgical debridement, antimicrobials, outcome.

Results

A total of 11 patients with LVAD infection due to NTM have been described in the literature. Four cases of NTM LVAD infection culminated in heart transplantation. Cases are summarized in Table 1. All transplanted cases had an indolent presentation and driveline discharge, without systemic symptoms. All underwent I&D and/or de-roofing of the driveline and were treated with at least two active antimicrobials for an extended course ranging from 4 months and up to 17 months after transplant. All cases did well from the infection standpoint. One died within 12 months from transplant rejection.

Conclusion

Treatment with a combination with at least two active agents is recommended and continued for many months. Effective surgical debridement of affected tissue and unroofing of the driveline beyond the affected velour, along with the removal of the infected device at the time of cardiac transplant, is key to success.

Disclosures

Susan J. Rehm, MD, Lilly (Individual(s) Involved: Self): Shareholder; Merck (Individual(s) Involved: Self): Shareholder; Pfizer (Individual(s) Involved: Self): Shareholder
966. ID Fellows Cup: Leveraging Gamification and Social Media to Enhance Clinical Infectious Diseases Education
Authors: Herrera Lauren Nicholas , Nolan Nathan , Chavez Miguel A , Kahn Mauricio J , Cleveland John D , McCarty Todd P , Escota Gerome , Kulkarni Prathit A , Patel Mukesh , Rodriguez Jorge M , Hunsinger Hillary P , Dempsey Donald , Willig James , Walker Jeremey
Published: December 2021

Background

We hypothesized that we could leverage social media to recruit learners to a gamification-infused ID knowledge competition, and entice them to explore additional online educational resources.

Methods

We created the ID Fellows Cup, a knowledge-based trivia competition, to engage Infectious Diseases fellows. The game was crafted via Kaizen-Education, a software platform developed at the University of Alabama at Birmingham, that uses gamification to engage learners. Multiple choice questions including figures and/or text are presented to learners, followed by detailed teaching explanations. 60 questions emphasizing high-yield concepts were delivered over 4 weeks. Questions were written by fellows and reviewed by faculty at three programs. Elements of gamification (virtual rewards, leaderboards, etc.) were included to enhance engagement. Recruitment strategies included Twitter, program director emails, and peer-to-peer. We measured game statistics and participation. Learners were invited to complete a post-game survey about their experience.

Results

Table 1 shows our game statistics with broad geographic reach including 42 programs. Most fellows matriculated in 2019 or 2020; the number of US ID fellows equaled 17% of those completing ID in-training exam. Recruitment sources included 44% co-fellow, 42% Twitter, and 15% Program Director. Through 20 days with questions, we had 155 daily average users. Overall, fellows answered 11,419 total questions, representing 89% of all released questions. Of 103 responses to post-game survey (table 2) 97% would participate again and all felt the game was a good use of their time. Over 80% of participants reported some engagement with linked resources included in the answer explanations. In general, 78% felt engagement with online resources increased subsequent to participating in the game, including learning about at least one new online resource.

Conclusion

We leveraged social media and gamification to effectively engage, and stimulate ID learners to explore additional online educational resources. Technology enriched learning, helps supplement and globalize ID education, making it as diverse and engaging as our field.

Disclosures

Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Prathit A. Kulkarni, M.D., Vessel Health, Inc. (Grant/Research Support)
975. Posaconzole for Treatment of Blastomycosis: An Academic Medical Center’s Experience
Authors: Baca Alec , Daniels Anne R , Sanchez Joyce L
Published: December 2021

Background

Blastomycosis is a serious environmentally acquired infection that is endemic to parts of North America. Treatment with antifungal agents is recommended for all patients with blastomycosis. Current guidelines recommend treatment with amphotericin B in severe disease and triazoles such as itraconazole, voriconazole, or fluconazole. All of these agents are known to have considerable toxicities. To date, only isolated case reports have been published describing the use of the newer, generally well-tolerated, posaconazole for this indication. Here we describe an academic medical center’s experience treating patients with blastomycosis in Wisconsin using posaconazole.

Methods

A retroactive chart review of electronic medical records was conducted of patients diagnosed with blastomycosis at Froedtert and The Medical College of Wisconsin. Nine blastomycosis patients were identified as being treated with posaconazole. Information was collected regarding patient demographics, comorbidities, risk factors, diagnostics, treatment history and clinical outcomes.

Results

The most common reasons for switching from itraconazole or voriconazole to posaconazole were adverse effects or inadequate triazole serum concentrations. Patients were relatively equal in gender and had an average age of 46 years old. All except one patient had an underlying immunocompromising condition, most commonly solid organ transplant. Two patients reported fatigue, weight gain, and memory problems after initiation of posaconazole. No patients had the drug discontinued due to adverse effects. Four patients were confirmed to be cured from blastomycosis, though some remained on long-term prophylactic therapy. Duration of treatment with posaconazole ranged from 1 to 60 months. Two patients died from causes unrelated to their infection or treatment.

Conclusion

Overall, the results of this study support posaconazole as a potential alternative to fluconazole, voriconazole, and fluconazole in the treatment of blastomycosis. Randomized controlled trials are needed to determine the efficacy and tolerability of posaconazole in comparison to other triazoles recommended in the current treatment guidelines.

Disclosures

All Authors: No reported disclosures
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

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

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 > 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 < 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

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

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

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 > 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

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

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

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)
1080. Relebactam Increases Imipenem Activity Against Imipenem-Nonsusceptible and -Susceptible Pseudomonas aeruginosa and Enterobacterales: Assessment of Isolates from RESTORE-IMI 2
Authors: Hilbert David W , Andrew DeRyke C , Losada Maria C , Moise Pamela , Chen Luke F , Young Katherine
Published: December 2021

Background

Relebactam (REL) inhibits class A and C β-lactamases (BLs) and is approved in the US in the combination imipenem/cilastatin/REL (IMI/REL) for hospital acquired bacterial pneumonia (HABP) and ventilator associated bacterial pneumonia (VABP), and also in patients with limited treatment options for complicated urinary tract infections and complicated intraabdominal infections. The objective of this study was to evaluate the potentiation of imipenem (IMI) by REL in baseline respiratory isolates from the recently completed Phase 3 RESTORE-IMI 2 study that demonstrated efficacy and safety of IMI/REL in the treatment of patients with HABP/VABP.

Methods

Baseline lower respiratory tract (LRT) isolates were evaluated for IMI MICs in the presence and absence of REL using broth microdilution and CLSI interpretive criteria. All Pseudomonas aeruginosa and Enterobacterales for which IMI/REL is either indicated or the MIC90 is less than or equal to the susceptibility breakpoint were evaluated.

Results

Summary statistics and the MIC distribution for P. aeruginosa are shown in the figure. For P. aeruginosa, REL reduces the IMI mode MIC of IMI-nonsusceptible (IMI-NS) (MIC >2) isolates ≥8-fold (from 16-32 to 2 µg/mL) and that of IMI-susceptible (IMI-S) (MIC ≤2) isolates ≥2-fold (from 1 to ≤0.5 µg/mL). Among Enterobacterales, the IMI mode MIC of IMI-NS (MIC >1) isolates was reduced ≥4-fold (from 2 to ≤0.5 µg/mL). REL enhanced the activity of IMI among IMI-S isolates (MIC ≤1), most notably observed in Enterobacterales species that produce a chromosomal AmpC, increasing the proportion with MIC ≤0.5 µg/mL from 76% to 98%.

MIC Distribution and Summary Statistics of RESTORE IMI-2 Isolates

Conclusion

Among baseline LRT isolates from RESTORE-IMI 2 the potentiation of IMI by REL results in the restoration of susceptibility among IMI-NS P. aeruginosa and Enterobacterales and enhanced IMI activity among IMI-S isolates. This enhanced activity among IMI-S Enterobacterales is most notable among species with reported chromosomal expression of AmpC. This lowering of IMI MICs upon addition of REL contributes to the high probability of target attainment (≥90%) observed following administration of IMI/REL 1.25g every 6 hours, further supporting the IMI/REL efficacy data observed in RESTORE-IMI 2.

Disclosures

David W. Hilbert, PhD, Merck (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Maria C. Losada, BA, Merck (Employee) Pamela Moise, PharmD, Merck (Employee) Luke F. Chen, MBBS MPH MBA FRACP FSHEA FIDSA, Merck (Employee) Katherine Young, MS, Merck (Employee)
1100. A Prospective Evaluation of Neurotoxicity Among Patients Receiving Dose-Optimized Cefepime or Meropenem With Concomitant Therapeutic Drug Monitoring
Authors: Smith Brandon , Kline Ellen G , Shutter Lori , Fong-Isariyawongse Joanna , Urban Alexandra , Murray Holt , Byers Karin , Shields Ryan K
Published: December 2021

Background

Cefepime (FEP) induced neurotoxicity (NT) may have serious implications for patients (pts). Retrospective studies have employed variable definitions of NT, finding renal impairment and FEP trough concentrations (Cmin) > 20 mg/L as risk factors. Prospective studies comparing antibiotics have not been performed.

Methods

We conducted a prospective study of pts receiving FEP or meropenem (MEM) with neurologic evaluation and therapeutic drug monitoring (TDM). A NT advisory board (NTAB) was established to develop standardized definitions of possible, probable and definitive NT (Fig 1). Cases of potential NT were adjudicated by the NTAB who were blinded to study treatment. FEP and MEM midpoint and Cmin concentrations were measured at steady-state by validated methods.

Results

127 patients were included (70 FEP, 57 MEM). Demographics and treatment characteristics were similar between groups (Fig 2); 63% were in the ICU. FEP and MEM Cmin varied from 1.9 – 140.5 and 0.6 – 31.3 mg/L, respectively. Median FEP Cmin and total exposures (AUC) were 23.1 mg/L and 347.6 hr*mg/L, respectively. Corresponding MEM values were 5.9 mg/L and 124.8 hr*mg/L, respectively. Cmin values were inversely correlated with renal function for both FEP and MEM (P< 0.001). Rates of possible, probable, or definitive NT were 10% and 5% for FEP and MEM, respectively (P=0.51; Fig 3). 16% and 3% of pts with FEP Cmin > or < 20 mg/L had NT, respectively (P=0.11; Fig 4). Median MEM Cmin were 12.3 and 5.4 mg/L among pts with and without NT, respectively (P=0.09; Fig 4). Rates of NT did not vary by infusion length or dose. FEP and MEM exposures were similar between patients with (17%) or without (83%) microbiologic recurrence due to the same pathogen. FEP was discontinued in 4 pts due to NT; no pts stopped MEM due to NT.

Conclusion

Our study is the first to evaluate FEP NT prospectively and compare rates of NT to pts receiving MEM. We established criteria that were applied by a blinded NTAB. In doing so we found rates of NT to be lower than previously reported and not statistically different between FEP and MEM. Cmin values were highly variable and associated with numerically, but not statistically higher rates of NT for both agents. These findings serve as the basis for larger, multicenter studies and justify use of routine TDM to limit NT among high-risk pts.

Disclosures

Brandon Smith, MD, PharmD, Shionogi (Consultant, Advisor or Review Panel member) Alexandra Urban, MD, Neuropace (Consultant) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support)
1125. Decreasing Concomitant Vancomycin and Piperacillin-Tazobactam Use in Children to Reduce Incidence of Acute Kidney Injury
Authors: Lamb Gabriella S , Lamb Gabriella S , Traum Avram , Khoury Zana , Yim Ramy , Jones Sarah , Nakamura Mari M
Published: December 2021

Background

Concomitant use of vancomycin (V) and piperacillin-tazobactam (PT) is associated with increased incidence of acute kidney injury (AKI). AKI develops 3 times faster on this combination compared to alternative vancomycin combinations. We sought to reduce AKI in our patients by reducing concomitant use of V/PT using a QI framework.

Methods

We implemented several PDSA cycles to reduce concomitant V/PT use at a 415-bed quaternary children’s hospital in Boston, MA. Interventions included substitution of PT with other agents in surgical prophylaxis guidelines and order sets starting in February 2020 and in the hospital-wide sepsis order set in March 2021. The Antimicrobial Stewardship Program reinforced these changes during daily audit-and-feedback reviews. In November 2020, we implemented an electronic alert that apprises clinicians of the AKI risk when V/PT are ordered and recommends an alternative regimen. We measured the monthly number of patients on combination V/PT, new exposures to nephrotoxic medications, AKI events, and the percentage of days with serum creatinine monitoring for patients on ≥2 nephrotoxic medications.

Results

From 02/01/20 to 05/31/21, the number of patients exposed to combination V/PT decreased from 23 to 6 per month (Figure 1). New nephrotoxic medication exposures declined from 17.1 to 7.7 per 1,000 patient days, and AKI events dropped from 2.8 to 0.6 per 1,000 patient days (Figures 2 and 3). The percentage of days with serum creatinine monitoring increased from 60% to 66%.

Rate of New Exposures to Nephrotoxic Medications per 1000 Patient Days

Conclusion

Revising guidelines and electronic order sets and implementing an order alert led to marked decreases in exposures to V/PT and nephrotoxic medications overall and was associated with reduced AKI events. Use of electronic health record tools is an effective way to drive safer antimicrobial use.

Disclosures

Gabriella S. Lamb, MD, MPH, Nothing to disclose
1157. Determining the Clinical Utility of 16S rRNA in the Management of Pediatric Infections
Authors: Lim Peter Paul , Desai Ankita P , Cherian Sree Sarah , Malay Sindhoosha
Published: December 2021

Background

Conventional culture remains the gold standard to facilitate a targeted antimicrobial regimen in the treatment of bacterial infections. However, certain pediatric infections are caused by fastidious organisms and treatment with antibiotics prior to specimen collection may hamper growth of pathogens in routine culture. The use of 16S rRNA in culture negative infections has improved identification of bacterial pathogens in select scenarios. However, the specific impact of 16S rRNA on clinical decision making, especially in pediatric infections, is not well-defined. This study aims to elucidate the utility of 16S rRNA on clinical management of pediatric infections.

Methods

A retrospective analysis was done on different clinical specimens which had 16S rRNA performed from August 2016 – March 2020 in our institution. Detailed chart review was performed to determine how the 16S rRNA result impacted clinical decision making. Clinical utility was defined as change in patient’s overall antimicrobial regimen, pathogen confirmation, and treatment duration.

Results

Seventy-four samples from 71 pediatric patients were included in the analysis: 32 (43%) were fluid specimens and 42 (57%) were tissue specimens. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p < 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n=9, 30%) followed equally by joint fluid (n=6, 20%) and bone (n=6, 20%). There was no significant difference in clinical utility between fluid and tissue specimens (p= 0.346). In 64 patients whose antimicrobial spectrum coverage was analyzed, patients with broad spectrum coverage was decreased from 48 to 21 and narrow spectrum coverage increased from 16 to 43 using 16S rRNA result, though not significant (p= 0.4111). Of all patients included in the analysis, the median number of antibiotics used before 16S rRNA result, 2, was significantly decreased to 1 (p < 0.0001).

Conclusion

16S rRNA has a significant impact in terms of decreasing number of antibiotics used in treatment of pediatric infections. Pulmonary specimens have the highest clinical utility among all samples. Additional cost benefit analysis needs to be completed to further determine clinical benefit.

Disclosures

All Authors: No reported disclosures
1164. Acquisition of Methicillin-Susceptible Staphylococcus aureus in the Neonatal Intensive Care Unit: Molecular Comparison of Relatedness of Isolates
Authors: Eid Dalia F , Gomez-Simmonds Angela , Boyar Vitaliya , Uhlemann Anne-Catrin , Rubin Lorry G
Published: December 2021

Background

In the NICU MSSA infections occur frequently and cause morbidity and mortality. Colonization is a risk factor for infection. Optimal infection prevention strategies await a more complete understanding of acquisition and transmission. To investigate possible transmission, we studied whether newly MSSA colonized infants share a strain with another contemporaneously colonized infant.

Methods

This is a prospective observational study in a level IV NICU from April through November 2019. Infants had weekly MSSA nasal surveillance cultures. Isolates from newly MSSA colonized infants and other infants colonized with MSSA during the same/previous week were subjected to staphylococcal protein A (spa) typing; most pairs with a concordant (CC) spa type were analyzed by whole genome sequencing (WGS; Illumina MiSeq). Pairs of isolates with a CC spa type and < 25 single nucleotide polymorphism differences on WGS were considered closely related (CC pairs). A control group consisted of pairs of isolates from a newly colonized infant with one randomly chosen colonized infant with a discordant (DC) spa type during the same/previous week. The medical records were reviewed for staff member (SM) and room assignment. Fischer’s exact test was used to compare proportions.

Results

Isolates from 60/68 consecutive newly MSSA colonized infants and 111/133 comparison infants were available for spa typing. Of these 60 infants, 23 (38 %) had a CC spa type with another infant colonized during the same/previous week. Of 18 isolate pairs from infants with a CC spa type that were subjected to WGS, 12 (67%) pairs of isolates were closely related. 7/12 (58 %) of CC pairs had a SM in common compared to 2/13 (15 %) in the DC pair groups, p=0.04. 2/12 (17 %) of CC pairs shared a room compared to 2/13 (15 %) pairs in the DC group, p=1.0.

Conclusion

Among newly MSSA colonized infants at least 25% are colonized with an isolate closely related to that of another colonized infant indicating likely infant to infant transmission. WGS is more discriminatory than spa typing for MSSA. Given the lack of commonality of room assignment and the commonality of SM assignment, a possible role of healthcare personnel in MSSA transmission should be further investigated.

Disclosures

Anne-Catrin Uhlemann, MD, PhD, Merck (Grant/Research Support)
1165. Seroprevalence of Chagas Disease among Latin American Children Living in New York
Authors: Handel Andrew S , Hellman Harriet , Flores Egar , Beneri Christy
Published: December 2021

Background

Approximately 300,00 individuals in the United States are estimated to have Chagas disease. To date, only one seroprevalence study in the US has included children. Diagnosis during childhood prevents irreversible sequelae and is better tolerated than during adulthood. Seropositive children may be difficult to identify, as those infected vertically may have never visited an endemic region. We sought to identify children with Chagas disease through a pilot study of serology and risk factors.

Methods

Participants were recruited from Stony Brook University Hospital (SBUH) or an ambulatory pediatric office, both in Suffolk County, New York (population: 1,476,000; 20.2% Hispanic or Latino). Study participants were 1 - 25 years old, resided in Suffolk County, and either the child and/or the child’s mother was born in or had long-term residence (≥ 3 years) in Latin America. T. cruzi serum IgG was determined with a Chagatest ELISA (Weiner Lab) or a Chagas Detect Plus Rapid Test (InBios). Positive screens were confirmed with a second serologic test at the CDC. Participants completed a survey of demographics and Chagas disease knowledge and risk factors, in English or Spanish. Descriptive statistics were applied. SBUH IRB provided study approval.

Results

We enrolled 93 children (Table 1). Three (3.2%) had a positive IgG screen, of which only one had a confirmed infection (1.1%). This was a 17-year-old who had lived in a rural adobe home and moved to the US at 8 years old. No children or their mothers recalled being bitten by or seeing triatomine insects in their Latin American homes. Of 27 children whose mothers had been screened for infection, 13 were born to 3 mothers with confirmed Chagas disease; all 13 children were seronegative. Of 8 participants reporting other family members with Chagas disease, all were seronegative.

Demographics of 93 participants screened for Chagas disease

SD

standard deviation; US: United States

Conclusion

Without reliable tools for identifying those at greatest risk of Chagas disease, universal screening of children born in high-risk Latin American regions remains a reasonable strategy. In addition, screening mothers born in Latin America is likely a more cost-efficient means to evaluate second-generation children. A tremendous knowledge gap of pediatric Chagas disease in the US remains.

Disclosures

All Authors: No reported disclosures