bluuebunny/crossref_metadata_2025 huggingface dataset:
1408. Enterovirus D68 RNA Visualized in the Anterior Horn of the Spinal Cord of a Pediatric Patient with Flaccid Paralysis
Authors: Vogt Matthew R , Wright Peter , Hickey William , Crowe James E , Boyd Kelli
Published: January 2021

Background

Acute flaccid myelitis (AFM) is a polio-like paralyzing illness of children. AFM incidence is increasing during every other year outbreaks that occur in the United States simultaneously with outbreaks of enterovirus D68 (EV-D68) infection. Demonstrating that EV-D68 directly causes AFM has been challenging due to rare detection of the virus in the cerebrospinal fluid (CSF) of patients despite frequent detection at nonsterile sites. Murine studies have shown that EV-D68 can infect spinal cord anterior horn motor neurons and cause paralysis, similar to poliovirus. However, a key outstanding question is whether EV-D68 causes AFM in humans by direct viral pathogenesis or by indirect host immunopathogenesis.

Methods

We investigated the pathogenesis of AFM using tissues from a previously reported case of a 5-year-old boy who presented in fall 2008 with four days of progressive limb and voice weakness followed by incontinence, apnea, and death. He had a CSF pleocytosis of 2094/µL with EV-D68 identified in the CSF by sequencing of the VP1 gene. We designed probes for in situ hybridization (ISH) based on this sequence to stain formalin fixed paraffin embedded tissues from his autopsy. For immunohistochemistry (IHC) we used both commercial polyclonal anti-EV-D68 antibodies and our own human monoclonal antibodies that stain virus infected cells in vitro. Immunophenotyping was done by IHC.

Results

With ISH we identified EV-D68 RNA in the anterior horn of the patient’s spinal cord, corresponding to the location of motor neuron cell bodies. This area was highly inflamed, with an infiltrate of lymphocytes and macrophages. Viral RNA was in low abundance, and we could not detect viral surface proteins by IHC. Neither RNA nor viral antigen was detected in the lungs, which had extensive inflammatory infiltrate.

Conclusion

Deaths in AFM patients are rare and often distant from initial presentation, but this patient died four days after onset of weakness, allowing us to directly demonstrate that EV-D68 can infect the human spinal cord. Low abundance of virus suggests the virus either reached the spinal cord prior to weakness onset or was cleared rapidly by the immune response. Therefore, both direct viral pathology and immune factors likely contribute to AFM disease in EV-D68 infection.

Disclosures

James E. Crowe, Jr, MD, IDBiologics (Board Member, Consultant, Grant/Research Support)Vanderbilt University (Other Financial or Material Support, Inventor on patent related to this abstract)
1409. Genomic Variation Among Respiratory Syncytial Viruses
Authors: Anderson Christopher S , Zhang Yun , Corbett Anthony , Chu Chin-Yi , Wang Lu , Qiu Xing , McCall Mathew , Topham David , Mariani Tom , Walsh Edward E , Scheuermann Richard , Caserta Mary T
Published: January 2021

Background

Respiratory Syncytial Virus (RSV) can be easily classified into two subtypes (A and B) based on the nucleic acid sequence of their genome. Phylogenic approaches have shown that within both subtypes separate lineages of viruses exist and new lineages continue to emerge. The role these genomic variations play in disease severity during RSV infection is largely unknown.

Methods

Next-generation viral RNA sequencing was performed on archived frozen nasal swabs of children infected with RSV in Rochester, NY between 1977-1998. Genomic variation was compared across year-of-isolation, age of host, and inpatient/outpatient status of host. Local RSV genomic variation was compared to variation of publicly available sequences isolated from hosts residing in other parts of the world.

Results

A and B subtypes demonstrated significant differences in the genetic sequence and primary-protein structure over time. G-protein was the most variable in both subtypes, but they differed in the number of unique genotypes detected. We found a significant association with disease severity (inpatient/outpatient status) and RSV phylogenetic topology, although the magnitude of the association differed by subtype. Variation in the primary protein structure of RSV viral proteins was also significantly associated with disease severity, but depended on which viral protein, and which subtype, was investigated. Lastly, local RSV genomic and protein-structure variation was similar to what was seen globally during this time period.

Conclusion

Overall, both subtypes demonstrated significant genetic change over time and these changes were associated with disease severity. These results suggest that the genetic variability of RSV may affect RSV disease in humans.

Disclosures

All Authors: No reported disclosures
1410. Neonatal Herpes Simplex Virus (HSV) Infection: Is It the Only Pathogen?
Authors: Dendi Alvaro , Garcia Ingrith Viviana Hoyos , Mejias Asuncion , Hanlon Cory T , Sanchez Pablo J
Published: January 2021

Background

Neonatal HSV infection is associated with substantial morbidity and mortality. Therefore, prompt identification and treatment of infected neonates is paramount. At Nationwide Children’s Hospital (NCH), Columbus, OH all neonates admitted in the first 2 weeks (up to 2010) and 4 weeks (since 2010) of age are evaluated for HSV infection in addition to routine bacterial and other viral infections. The frequency of co-infection with HSV and other potential pathogens is not fully known.

Methods

Retrospective review of the medical records of infants admitted to NCH with a diagnosis of neonatal HSV infection from 2001 to 2019. Patients less than 6 weeks of age were identified by review of the NCH Virology and Molecular Laboratory results for all positive HSV PCRs obtained from any body site as well as by discharge ICD-9 and ICD-10 codes for HSV infection. Medical records were reviewed for demographic, clinical, laboratory, outcome data, and maternal history of genital HSV lesions at or before delivery. Occurrence of positive bacterial and/or viral co-detection were identified. The data were managed using REDCap electronic data capture tools hosted at NCH.

Results

There were 93 infants with neonatal HSV infection (mean age, 9.5 days [IQR, 7-15]; 42%, HSV1; 53%, HSV-2). 32 infants had central nervous system infection (CNS) while 31 had Skin-Eye-Mouth (SEM) infection and 30 had Disseminated Disease. Mortality was 15% (n=14). Only 3 mothers had active genital HSV lesions at delivery. Of the 93 infants, 5 (5%) had bacterial (n=2) or viral (n=3) co-infections. All of the infants only had mucosal sites positive for HSV 1 (n=4) or 2 (n=1). Of the 2 infants with bacterial infection, 1 had bacteremia due to viridans streptococci while the other one had necrotizing enterocolitis and a positive blood culture for Clostridium butyricum. The 3 infants with viral co-detection also were full term and all had positive enterovovirus PCR tests (1, blood, throat; 1, blood and ceerebrospinal fluid (CSF); 1, CSF)

Conclusion

5% of infants with neonatal HSV infection had bacterial or enteroviral co-infection. These findings have important implications in the management of neonates evaluated for possible sepsis.

Disclosures

Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)
1412. The utility of respiratory viral panel testing for nosocomial fever in the neonatal intensive care unit
Authors: Palacios Carlo Fopiano , Lemmon Eric , Campbell James
Published: January 2021

Background

Patients in the neonatal intensive care unit (NICU) often develop fevers during their inpatient stay. Many neonates are empirically started on antibiotics due to their fragile clinical status. We sought to evaluate whether the respiratory viral panel (RVP) PCR test is associated with use of antibiotics in patients who develop a fever in the NICU.

Methods

We conducted a retrospective chart review on patients admitted to the Level 4 NICU of the University of Maryland Medical Center from November 2015 to June 2018. We included all neonates who developed a fever 48 hours into their admission. We collected demographic information and data on length of stay, fever work-up and diagnostics (including labs, cultures, RVP), and antibiotic use. Descriptive statistics, Fisher exact test, linear regression, and Welch’s ANOVA were performed.

Results

Among 347 fever episodes, the mean age of neonates was 72.8 ± 21.6 days, and 45.2% were female. Out of 30 total RVP samples analyzed, 2 were positive (6.7%). The most common causes of fever were post-procedural (5.7%), pneumonia (4.8%), urinary tract infection (3.5%), meningitis (2.6%), bacteremia (2.3%), or due to a viral infection (2.0%). Antibiotics were started in 208 patients (60%), while 61 neonates (17.6%) were already on antibiotics. The mean length of antibiotics was 7.5 ± 0.5 days. Neonates were more likely to get started on antibiotics if they had a negative RVP compared to those without a negative RVP (89% vs. 11%, p-value < 0.0001). Patients with a positive RVP had a decreased length of stay compared to those without a positive RVP (30.3 ± 8.7 vs. 96.8 ± 71.3, p-value 0.01). On multivariate linear regression, a positive RVP was not associated with length of stay.

Conclusion

Neonates with a negative respiratory viral PCR test were more likely to be started on antibiotics for fevers. Respiratory viral PCR testing can be used as a tool to promote antibiotic stewardship in the NICU.

Disclosures

All Authors: No reported disclosures
1414. #Vaccine Twitter Influencers: is it Just About Reach and Followers?
Authors: Poirrier Jean-Etienne , Caputi Theodore , Ayers John , Dredze Mark , Poston Sara , Hogea Cosmina
Published: January 2021

Background

A small number of powerful users (“influencers”) dominates conversations on social media platforms: less than 1% of Twitter accounts have at least 3,000 followers and even fewer have hundreds of thousands or millions of followers. Beyond simple metrics (number of tweets, retweets...) little is known about these “influencers”, particularly in relation to their role in shaping online narratives about vaccines. Our goal was to describe influential Twitter accounts that are driving conversations about vaccines and present new metrics of influence.

Methods

Using publicly-available data from Twitter, we selected posts from 1-Jan-2016 to 31-Dec-2018 and extracted the top 5% of accounts tweeting about vaccines with the most followers. Using automated classifiers, we determined the location of these accounts, and grouped them into those that primarily tweet pro- versus anti-vaccine content. We further characterized the demographics of these influencer accounts.

Results

From 25,381 vaccine-related tweets available in our sample representing 10,607 users, 530 accounts represented the top 5% by number of followers. These accounts had on average 1,608,637 followers (standard deviation=5,063,421) and 340,390 median followers. Among the accounts for which sentiment was successfully estimated by the classifier, 10.4% (n=55) posted anti-vaccine content and 33.6% (n=178) posted pro-vaccine content. Of the 55 anti-vaccine accounts, 50% (n=18) of the accounts for which location was successfully determined were from the United States. Of the 178 pro-vaccine accounts, 42.5% (n=54) were from the United States.

Conclusion

This study showed that only a small proportion of Twitter accounts (A) post about vaccines and (B) have a high follower count and post anti-vaccine content. Further analysis of these users may help researchers and policy makers better understand how to amplify the impact of pro-vaccine social media messages.

Disclosures

Jean-Etienne Poirrier, PhD, MBA, The GSK group of companies (Employee, Shareholder) Theodore Caputi, PhD, Good Analytics Inc. (Consultant) John Ayers, PhD, GSK (Grant/Research Support) Mark Dredze, PhD, Bloomberg LP (Consultant)Good Analytics (Consultant) Sara Poston, PharmD, The GlaxoSmithKline group of companies (Employee, Shareholder) Cosmina Hogea, PhD, GlaxoSmithKline (Employee, Shareholder)
1415. A qualitative study of intersectional stigma among older adults living with HIV who are victims of childhood sexual abuse
Authors: Nkwonta Chigozie A , Brown Monique , James Titilayo , Kaur Amandeep
Published: January 2021

Background

Intersectional stigma is based upon co-occurring and intersecting identities or conditions and occurs at multiple levels of influence. Intersectional stigma has been repeatedly associated with poor health behaviors and outcomes. The effect of intersectional stigma among older adults are particularly challenging due to issues related to ageism, loss of social support, and comorbidities. We examined the impact of multiple stigmas on older adults living with HIV who are victims of childhood sexual abuse.

Methods

Semi-structured interviews were conducted with a purposefully selected heterogeneous sample of 24 adults living with HIV who are 50 years and older in South Carolina. Interviews were audio-recorded, transcribed verbatim, and coded using thematic analysis.

Results

Participants shared experiences and perceptions of stigma and discrimination most commonly related to their HIV status and sexuality at the interpersonal/familial and community levels. Four themes emerged to explain the impact of intersectional stigma: depression, lack of HIV disclosure, limited support, and reduced intimacy.

Conclusion

The complexity of multiple stigmas profoundly shapes life experiences, opportunities, and mental health of older adults living with HIV. This study highlights that public health programs need to consider the impact of intersectional stigma in order to promote the wellbeing of and improve quality of life for older adults living with HIV.

Disclosures

All Authors: No reported disclosures
1418. Injections and Infections: Understanding Harm Reduction Utilization in a Rural State
Authors: Thakarar Kinna , Murray Kim , Sankar Nityasri , Carwile Jenny , Lucas F L , Burris Debra D , Borelli Timothy J , Pinsky Robert , Liechty Cheryl , Smith Robert P
Published: January 2021

Background

Increasing rates of injection drug use (IDU) associated-infections suggest significant syringe service program (SSP) underutilization. Our study objective is to assess patient knowledge, attitudes, and practices of safe injection techniques and to determine predictors of SSP utilization in a rural state.

Methods

This is a fifteen-month cross-sectional study of participants hospitalized with IDU-associated infections at four hospitals in Maine. Data were collected through Audio Computer-Assisted Self-Interview survey and medical record review. Descriptive analyses were performed to characterize injection knowledge, attitudes and practices. The primary outcome was past 3-month SSP utilization, and the main independent variable was self-reported distance to SSP. Secondary outcomes were uptake of clean drug equipment, naloxone, and treatment with medication for opioid use disorder. Logistic regression analyses were performed to identify factors associated with the primary outcome, controlling for gender, homelessness, history of overdose, having primary care physician and distance to SSP.

Results

Of the 101 study participants, 62 participants (65%) reported past 3 month SSP utilization, though only 33% used SSPs frequently. Few participants (10%) reported clean needle/syringe use or clean drug equipment use (5%). Forty-eight percent of participants reported naloxone uptake, and 66% of participants were prescribed medication for opioid use disorder prior to admission. Many participants (59%) lived more than 10 miles from an SSP with 18% of participants living in rural areas. Fifty-four percent reported difficulty accessing an SSP. Participants who lived less than 10 miles of an SSP were more likely to use it (adjusted odds ratio 5.47; 95% CI 2.1- 14.3).

Conclusion

Our study highlights unsafe injection practices and lack of frequent SSP utilization among people admitted with IDU-associated infections in Maine. Especially given increasing stimulant use in our state and nationally, these results also highlight the need to promote harm reduction even among individuals prescribed medication for opioid use disorder. Particularly in rural areas where patients may live more than 10 miles from an SSP, expansion of harm reduction services should be a priority.

Disclosures

All Authors: No reported disclosures
1419. National ambulatory health resource utilization and geographic disparities of influenza in the United States, 2009 to 2016
Authors: Young Eric H , Crowell Richard , Gonzalez Anjeanette , Reveles Kelly R
Published: January 2021

Background

Influenza can affect up to 10% of adults and 30% of children and, in specific populations, can lead to severe illness and death. Although epidemiological surveillance on influenza patterns have been expanded since 2009, it is also imperative to observe specific trends for influenza immunization and treatment to inform and potentially prevent future outbreaks. The primary objective of this study was to describe influenza prevalence, immunization, and treatment among outpatients in the United States (US).

Methods

This was a cross-sectional study using the Centers for Disease Control and Prevention’s National Ambulatory and Hospital Ambulatory Medical Care Surveys from 2009 to 2016. All patient visits were eligible for inclusion, and prevalence rates were described as influenza visits per 1,000 patient visits. Patient visits were categorized by year, month, and US geographic region. Influenza vaccinations and treatments were defined by their respective Multum code(s) and diagnosis was identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) and ICD-10 codes for the appropriate survey years. Data were presented descriptively.

Results

Over 7 billion visits were included for analysis. Overall, influenza rates varied over the study period with the highest rate in 2009 (5.0) and lowest in 2015 (0.9). Immunization rates were highest in 2014 (25.4) and lowest in 2016 (12.5). The South had the highest influenza rates (3.6) and proportion of influenza visits that included treatment (45.6%), as well as the lowest immunization rates (17.6). The Northeast had the lowest influenza rate (1.5), while the West had the lowest proportion of influenza treatment (24.9%) and highest immunization rates (23.4). December and February had the highest rates of influenza (5.2 and 5.7, respectively), while rates of immunization were the highest in September and October (48.9 and 71.7, respectively).

Conclusion

Immunization rates were highest in the fall months and influenza rates were highest in the winter months. Overall, this study found that regions with lower influenza vaccination had higher influenza rates, and vice versa. Future campaigns should promote immunizations against the influenza virus particularly in underserved regions (e.g., South).

Disclosures

All Authors: No reported disclosures
1423. Clinical Presentation Of Brucellosis: An Experience Of 29-Year Period
Authors: Hammami Fatma , Koubaa Makram , Smaoui Fatma , Chakroun Amal , Rekik Khaoula , Elleuch Emna , Marrakchi Chakib , Jemaa Mounir Ben
Published: January 2021

Background

Brucellosis is a multi-organ zoonotic disease which may present with a myriad manifestation. In our country, brucellosis remains endemic and represents a public health problem. We aimed to study the clinical, therapeutic and evolutionary features of brucellosis.

Methods

We conducted a retrospective study including all patients hospitalized for brucellosis in the infectious diseases department between 1990 and 2018. Positive blood cultures to Brucella spp and/or standard agglutination test (SAT) titer > 1/160 confirmed the diagnosis.

Results

During the study period, we encountered 216 cases of brucellosis, among whom 140 cases were males (64.8%). The mean age was 40±17 years. Patients came from rural areas (89.8%) and had a close contact with animals (70.8%). The consumption of unpasteurized milk was noted in 182 cases (84.2%). A family history of brucellosis was noted in 53 cases (24.5%). In total, 68 patients had a previous medical history of treated brucellosis (31.4%). There were 113 cases (52.3%) of acute brucellosis and 103 cases (47.7%) of sub-acute brucellosis. Spondylodiscitis (65 cases; 63.1%), neurobrucellosis (17 cases; 16.5%) and sacroiliitis (12 cases; 11.7%) were the most common forms of the sub-acute brucellosis. The revealing symptoms were fever (83.8%), night sweats (71.3%), arthralgia (55.1%) and back pain (53.2%). Laboratory investigations revealed leukopenia (14.4%), anemia (49%) and elevated C-reactive protein levels (42.1%). Blood cultures were positive to Brucella in 17.1% of the cases. Patients received a combination therapy based on doxycycline and rifampicin in 141 cases (65.2%). Triple therapy regimen including doxycycline, rifampicin and co-trimoxazole was prescribed in 51 cases (23.6%). The mean treatment duration was 52±20 days in the acute form and 6±3 months in the sub-acute form. The disease evolution was favourable in 94.4% of the cases. Sequelae were noted in 12% of the cases and relapse in 3.7% of the cases. Four patients were dead (1.9%).

Conclusion

Due to its various clinical presentation, the diagnosis of brucellosis might be delayed. High index of suspicion is required in order to promptly diagnose the disease. Control and eradication of brucellosis in animals are mandatory so as to eradicate brucellosis.

Disclosures

All Authors: No reported disclosures
1424. Factors Associated with Failure to Clear Candidemia Infection: Surveillance Data from Eight States, 2017
Authors: Oh David H , Seagle Emma , Lockhart Shawn R , Nadle Joelle , Barter Devra , Johnston Helen , Farley Monica M , Revis Andrew , Pattee Brittany , Phipps Erin C , Tesini Brenda L , Zhang Alexia Y , Schaffner William , Jackson Brendan R , Lyman Meghan
Published: January 2021

Background

Candidemia is a bloodstream infection commonly associated with high morbidity and mortality. Failure to clear candidemia can lengthen hospitalization and treatment. Factors associated with candidemia clearance are unknown.

Methods

We analyzed 2017 candidemia surveillance data from the Centers for Disease Control and Prevention’s Emerging Infections Program. Data from eight sites (counties in California, Colorado, Georgia, Minnesota, New Mexico, New York, Oregon, and Tennessee) were included. Clearance was defined as having a blood culture negative for Candida ≤30 days after initial culture date (ICD). Cases with unknown clearance, unknown survival outcome, or death ≤30 days of ICD were excluded. Demographic and clinical factors associated with clearance were assessed with bivariate analysis using chi-square tests and multivariable logistic regression to calculate adjusted odds ratios (aOR) using backward selection (p-value< 0.10).

Results

Of 1,024 candidemia cases, 737 were included and 582 (79%) demonstrated clearance, of which 79% had evidence of clearance ≤5 days after ICD. In bivariate analysis, clearance was associated with central venous catheter (CVC) ≤2 days before ICD, CVC removal ≤7 days after ICD, and systemic antifungal medication within 14 days before ICD. Clearance was inversely associated with black race and admission from another hospital. In multivariable analysis, only race and admission from another hospital were significant predictors; age, sex, and CVC presence and subsequent removal were also retained for their clinical relevance. In the final model, clearance was less likely among black patients (aOR 0.51, 95% confidence interval [CI] 0.29-0.91) and those admitted from another hospital (aOR 0.28, 95% CI 0.11-0.75).

Table 1. Bivariate associations for select variables between individuals with documented candidemia clearance and those without documented clearance in eight Emerging Infections Program surveillance sites, 2017

Conclusion

We found failure to clear candidemia infection to be associated with black race and prior hospital exposure, but not other factors previously shown to be associated (e.g., comorbidities, CVC presence). These associations could reflect illness severity, access to care, or other obstacles to effective treatment. Additional research is needed to investigate these associations further and identify other factors (e.g., treatment type and timing) to improve outcomes.

Disclosures

All Authors: No reported disclosures
1427. Key Clinical Research Questions Asked During Epidemic Respiratory Outbreaks: A Systematic Review of the Literature Published on Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome
Authors: Harris Carlyn L , Carson Gail , Nair Harish
Published: January 2021

Background

As evidenced by the COVID-19 pandemic, rapid collection of data on clinical characterization, treatment, and diagnostics to inform rapid public health response is paramount in an outbreak of a novel infectious agent. In 2018, The World Health Organization R&D Blueprint identified a list of priority diseases for accelerated research based on their potential to cause a public health emergency. Among these diseases were Severe acute respiratory syndrome-coronavirus (SARS-CoV) and Middle East respiratory syndrome-coronavirus (MERS-CoV). To facilitate a rapid research response during an outbreak, standardized research protocols must be prepared before the outbreak occurs. The aim of this systematic review is to identify the most common clinical research questions asked during outbreaks of SARS-CoV and MERS-CoV to inform future clinical research protocol development for coronaviruses.

Methods

Medline, Embase, and Global Health bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to the clinical research question addressed.

Results

From the research questions and objectives, eleven themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control, transmission, susceptibility, psychosocial, and aetiology. Case series made up the highest proportion of study designs, while clinical trials made up the lowest. 83% of the SARS-CoV studies were published after the end of the outbreak.

Themes and key clinical questions asked during outbreaks of SARS and MERS

Conclusion

The thematic analysis was used to identify the key clinical research questions asked during outbreaks of SARS-CoV and MERS-CoV and study designs were recommended to answer these questions. By defining the key clinical research questions, this study provides a first step in creating standardized clinical research protocols and defining core data variables to be collected during future outbreaks of respiratory coronaviruses.

Disclosures

All Authors: No reported disclosures
116. Leveraging the Use of the PCR-based Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Swab in the Emergency Department to Optimize Vancomycin Use in the Inpatient Setting
Authors: McManus Dayna , Topal Jeffrey E , Kassab Hagar
Published: January 2021

Background

The MRSA nasal swab has been shown to have a negative predictive value of 97–100% for an MRSA infection. Therefore, a negative MRSA swab can be an important antimicrobial stewardship tool to stop unnecessary empiric anti-MRSA therapy. Prolonged anti-MRSA therapy may increase hospital length stay, adverse effects, antimicrobial resistance, and increase the risk of acute kidney injury. Timely obtainment of the MRSA nasal swab is paramount to prevent these complications. To improve the timely collection at our institution, we linked the MRSA nasal swab order with the initial order for vancomycin in the ED using the electronic medical record.

Methods

This was a single-center, retrospective review of adult ED patients (≥ 18 years) who recieved vancomycin at Yale New Haven Hospital, New Haven, CT, USA and had an MRSA nasal swab collected. The pre-intervention cohort were patients who met inclusion criteria between September 2018 and October 2018. The post-intervention cohort, following the linking of the MRSA nasal swab with the vancomycin order included patients between June 2019 and July 2019. The primary endpoint was the time from the ED visit to vancomycin discontinuation in patients with a negative MRSA nasal swab. The secondary endpoint was a comparison of inpatient vancomycin usage before and after implimentation of the intervention.

Results

In the pre-intervention cohort 665 patients were reviewed with 100 meeting inclusion criteria and in the post-intervention cohort 242 patients were reviewed with 100 meeting inclusion criteria. Baseline demographic characteristics were similar between the two cohorts. For the primary endpoint, the time from ED visit until vancomycin discontinuation was 61 hours in the pre-intervention cohort versus 34 hours in the post-intervention cohort (p< 0.001). The secondary endpoint of the impact of the intervention on vancomycin usage is depicted figure attached.

Vancomycin IV Days of Therapy/1000 Patient Days Before and After Intervention

Conclusion

Linking the MRSA nasal swab order with the order for vancomycin in the ED led to a significantly shorter time of empiric vancomycin which in turn resulted in an overall reduction in the use of vancomycin.

Disclosures

All Authors: No reported disclosures
1441. Using Carbapenem Resistance Levels to Discriminate Between Carbapenemase Producing and Non-Carbapenemase Producing Carbapenem Resistant Enterobacteriaceae
Authors: Koehne William J , Peritz Tiina , Privette Kristin , Gould Jane
Published: January 2021

Background

Carbapenem-resistant Enterobacteriaceae (CRE) are a growing threat globally. Many CRE organisms carry plasmids that produce a carbapenemase enzyme (CP-CRE). Early detection of CP-CRE and aggressive infection prevention and control (IPC) measures are necessary to reduce transmission of resistant organisms and their plasmids. Many hospital laboratories do not test CRE for carbapenemase production. In Apr ‘18, the Philadelphia Department for Public Health (PDPH) established mandatory CRE reporting including isolate submission for mechanism testing at public health laboratories.

Methods

We analyzed trends of carbapenem resistance in CP and non-CP-CRE. We calculated sensitivity (Sen), specificity (Spe), positive and negative predictive values (PPV, NPV) at each level of carbapenem resistance to develop a predictive model with goal of effectively discriminating CP and non-CP CRE. ROC curves were plotted.

Results

From June,’18-Feb,’20, 351 CRE had genetic mechanism testing. 192 (54.7%) were Klebsiella pneumoniae, 53 (15.1%) were Enterobacter cloacae, 52 (14.8%) were E. coli, and the remaining 54 (15.4%) other Enterobacteriaceae.186 (53.0%) had a recorded minimum inhibitory concentration (MIC) for ertapenem, 191 (54.4%) for meropenem, 116 (33.0%) for imipenem, and 9 (2.6%) for doripenem. Doripenem was not further analyzed. The odds of being CP-CRE increased with increasing MIC. One standard dilution increase in MIC was associated with the following odds ratios (OR) of being CP-CRE: ertapenem OR 1.43 (95% CI: 1.11–1.83), imipenem OR 2.52 (95% CI: 1.7–3.793), meropenem, OR 2.20 (95% CI: 1.72–2.81). For each carbapenem, we calculated Sen, Spe, PPV, and NPV values for five MIC cut points; 0.5, 1, 2, 4, and 8 ug/ml, non-CP CRE defined as ≤ MIC cut point, CP-CRE defined as > cut point.

Figure 1. ROC Curves

Table 1. Sensitivity, Specificity, PPV, NPV of MIC Cut Points

Conclusion

There were no MIC cut points that performed well in both Sen and Spe, however, for the purposes of IPC, correctly classifying CP CRE (Sen) is more important than correctly classifying non-CP CRE (Spe). MIC cut points that performed best were imipenem MIC of 1 ug/ml and meropenem MIC of 1 ug/ml, with Sen 98%, 94% respectively, PPV 85%, 84% respectively and NPV 88%, 76% respectively. When further testing is not available, MIC cut points may be used to infer CP production.

Disclosures

All Authors: No reported disclosures
1446. Dynamics of Enterococcus faecalis Cardiolipin Synthase Gene Expression Reveal Compensatory Roles in Daptomycin Resistance
Authors: Nguyen April , Polamraju Vinathi , Tran Truc T , Panesso-Botero Diana , Khan Ayesha , Mileykovskaya Eugenia , Vitrac Heidi , Arias Cesar A
Published: January 2021

Background

Daptomycin (DAP) is a lipopeptide antibiotic targeting membrane anionic phospholipids (APLs) at the division septum, and resistance (DAP-R) has been linked to mutations in genes encoding i) the LiaFSR stress response system or its effector LiaX, and ii) cardiolipin synthase (Cls). Activation of the E. faecalis (Efs) LiaFSR response is associated with DAP-R and redistribution of APL microdomains away from the septum, and cardiolipin is predicted to be a major component of these APL microdomains. Efs harbors two putative cls genes, cls1 and cls2. While changes in Cls1 have been implicated in DAP-R, the exact roles of each enzyme in resistance are unknown. We aim to characterize the contributions of Cls1 and Cls2 in the development of DAP-R.

Methods

cls1 and cls2 were deleted individually and in tandem from DAP-S Efs OG117 and DAP-R Efs OG117∆liaX (a DAP-R derivative strain with an activated LiaFSR response). Mutants were characterized by DAP minimum inhibitory concentration (MIC) using E-test on Mueller-Hinton II agar and localization of APL microdomains with 10-N-nonyl-acridine orange staining. Quantitative PCR (qRT-PCR) was used to study gene expression profiles of cls1 and cls2 in Efs OG117∆liaX relative to Efs OG117 across the cell growth cycle.

Results

qRT-PCR revealed differential expression profiles of cls1 and cls2 associated with DAP-R. cls1 was highly upregulated in stationary phase concurrent with a decrease in cls2 expression. However, independent deletion of cls1 or cls2 in the DAP-R background resulted in no significant changes in DAP MICs or localization of APL microdomains (remaining non-septal). Further studies revealed that cls2 expression is upregulated upon deletion of cls1 in both the DAP-S and DAP-R background, suggesting a potential compensatory role for Cls2. Double deletion of both cls genes in the DAP-R strain decreased DAP MIC and restored the septal localization of APL microdomains.

Conclusion

Cls1 is the major and predominant enzyme involved in cell membrane adaptation associated with the development of DAP-R in E. faecalis. However, we describe a novel compensatory and overlapping role for cardiolipin synthases to ensure bacterial survival upon attack from antimicrobial peptides and related antibiotics.

Disclosures

Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)
1453. PBP2, PBP2a and PBP4 Clone-specific Polymorphisms are not Associated to Ceftaroline (CPT) Susceptibility in Chilean Clinical Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA)
Authors: Spencer Maria de los Angeles , Martinez José Rodrigo , Rivas Lina María , rojas Marcelo , Rios Rafael , Dinh An Q , Diaz Lorena , Reyes Jinnethe , Hanson Blake , Garcia Patricia , Arias Cesar A , Munita Jose M
Published: January 2021

Background

CPT is a last-generation cephalosporin active against MRSA due to its affinity for PBP2a. CPT-resistance (CPT-R) is well-described, with mutations in the active transpeptidase domain of PBP2a associated to high-level resistance. The accumulation of changes in the non-penicillin-binding domain of PBP2a has been linked to elevations of the minimal inhibitory concentration (MIC) to CPT to levels around 2-4ug/mL. PBP4 and PBP2 have also been implicated as potentially relevant mecA-independent mechanisms of CPT-R. We recently reported high rates of CPT-non-susceptibility in clinical MRSA strains from Chile. However, the mutational landscape of PBPs in clinical MRSA isolates from Chile and its relation to CPT susceptibility has not been assessed.

Methods

We analyzed 180 MRSA isolates collected from 2000-2018 in Santiago, Chile. Identification was confirmed by MALDI-TOF and methicillin resistance with cefoxitin disk-diffusion. CPT susceptibility was performed by BMD following CLSI-2019 guidance. Whole-genome sequencing was performed for all isolates; the mutational profile of PBPs was determined using reference sequences for PBP2 (AGY89563.1), PBP2a (NG_047938.1) and PBP4 (X91786.1).

Results

All isolates were phenotypically-confirmed MRSA and harbored mecA. The MIC50/MIC90 by BMD was 2/2μg/dL; only 71 (39%) isolates were CPT-susceptible (MIC <1µg/mL). Most isolates belonged to ST5/SCCmecI (70%,126/180), ST105/SCCmecII (10%,18/180) and ST8/SCCmecIV (5%, 9/180). All ST5/SCCmecI isolates carried the mutations in PBP2 (Y156D), PBP2a (M122I and E150K), and PBP4 (T189S, L234H, and T409A); CPT-susceptibility among ST5/SCCmecI was only 22%. On the other hand, all ST105/SCCmecII isolates had mutations in PBP2 (S707L) and PBP4 (T189S, L234H, and T409A) and exhibited a higher CPT-susceptibility rate (67%). All 9 isolates belonging to the ST8/SCCmecIV lineage harbored a non-coding mutation in PBP2a (g-6t) and the previously observed L234H change in PBP4. Importantly, no association between specific polymorphisms and MIC to CPT was found.

Table 1. PBPs mutations compared to CPT MICs by MLST and SCCmec

Conclusion

Changes in the studied PBPs were frequent among MRSA circulating in Chile and were conserved among different genetic backgrounds. However, these changes were not associated with the level of CPT MIC among these isolates.

Disclosures

Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)
1456. Resistance Mechanisms of Tigecycline in Enterococcus faecalis
Authors: Bai Bing , Wen Zewen , Lin Zhiwei , H Tam Vincent , Yu Zhijian
Published: January 2021

Background

Enterococcus faecalis have been regarded as one of the leading causes of the nosocomial infections worldwide. Tigecycline (TGC) is considered as a choice of last resort for the treatment of infections caused by multidrug-resistant E. faecalis, however, the emergence of TGC non-susceptibility has posted the therapeutic challenge. Non-susceptibility in clinical strains could be due to resistance (MIC >0.5 mg/l) or heteroresistance. Therefore, this study aimed to understand the underlying molecular mechanisms of TGC resistance and heteroresistance in E. faecalis.

Methods

In vitro induction experiments were carried out under TGC pressure with two TGC- sensitive E. faecalis strains. Heteroresistance was evaluated by population analysis profiling (PAP) in 270 clinical TGC- sensitive E. faecalis strains. TGC susceptibility was determined by the agar dilution method. Resistance and heteroresistance mechanisms were investigated by identifying genetic mutations in tetracycline (Tet) target sites and susceptibility testing in the presence of the efflux protein inhibitors phenylalanine-arginine-β-naphthylamide (PaβN) and carbonyl cyanide m chlorophenylhydrazine (CCCP). Comparison of single nucleotide polymorphism in the whole genome between the parental isolate and two TGC-resistant strains were investigated by next-generation sequencing.

Results

No mutations in Tet target sites in seven TGC heteroresistant strains were present, whereas the mutations in Tet target sites of seven TGC-resistant E. faecalis were frequently found (Table 1). TGC MICs in heteroresistant strains were reduced by CCCP (Table 2). Whole genome sequencing revealed the same non-synonymous mutations and transcoding deletions in the exons of several genes encoding for various enzymes or transfer systems (Table 3).

Table 1. The characteristics of the antimicrobial susceptibility, resistance mechanism of TGC-induced resistant isolates

Table 2. Characteristics of clinical heteroresistant mother E. faecalis strains and heteroresistance-derived E. faecalis clones

Table 3. List of mutation-related genes, amino acids and proteins by comparison of whole genome between the parental isolate and the TGC-induced resistant strains

Conclusion

Our data indicated that the main mechanism of TGC heteroresistance in E. faecalis might be associated with the efflux pumps. TGC resistance in E. faecalis was associated with mutations in the 16SrRNA site or 30S ribosome protein S10. The genetic mutations in several enzymes and transfer systems might also participate in the resistance development to TGC in E. faecalis.

Disclosures

All Authors: No reported disclosures
1457. Serial Passage of Enterobacteriaceae to Explore Development of Carbapenem Resistance
Authors: Nissim Yosef , Slain Douglas , LaSala P Rocco
Published: January 2021

Background

Carbapenems are broad-spectrum antibacterials that have seen increased usage for the Enterobacteriales family in recent years. While carbapenem usage has been associated with increased antibacterial resistance, there is currently a lack of data comparing the risk of reduced susceptibility selection by the two most commonly used carbapenems in the US, ertapenem (ERT) and meropenem (MER). We conducted a novel serial passage experiment with clinical isolates of Enterobacteriales to assess the impact of repeated exposure to ERT or MER on phenotypic susceptibility patterns.

Methods

Non-duplicate clinical Enterobacteriales isolates were selected randomly for inclusion. Antimicrobial susceptibility testing was performed by CLSI disc diffusion methods. Standardized suspensions of isolates were plated on Mueller-Hinton agar, and ERT (10mcg) and MER (10mcg) discs applied. Zones of inhibition were measured and recorded after 16-18 hours incubation. Growth from the innermost zone of inhibition around each disc was used to prepare subsequent suspensions for serial susceptibility testing. This process would be repeated daily for 10 days. Each subsequent serially-passaged isolated was tested against both ERT and MER. Daily zones of inhibition were measured and interpreted. Baseline & final susceptibilities were determined by automated methods (Vitek 2).

Results

Seventeen Enterobacteriaceae isolates were selected, including: Klebsiella pneumoniae (n=11), Klebsiella oxytoca (n=2), Escherichia coli (n=1), Morganella morganii (n=1), and Enterobacter cloacae (n=2). Despite a greater degree of reductions in zones of inhibition with repeated ERT exposure (vs MER), the overall 10 day trends were not found to be significant different (P=0.529). Resistance developed to ERT in six isolates compared to one MER-resistant isolate (P = 0.053). E. cloacae was the only species to show a significant change between drugs (P=0.010). Two of three isolates that developed reduced zone changes > 10mm to MER were initially exposed to ERT on an earlier plate.

Conclusion

This novel experiment identified the development of some nonsignificant reductions in susceptibility with ERT after serial exposure. Results from this pilot study should encourage larger well-designed studies in this area.

Disclosures

All Authors: No reported disclosures
1461. Impact of the Ampicillin/Sulbactam Shortage on Antibiotic Prescribing and Clinical Outcomes for Adult Inpatients with Aspiration Pneumonia
Authors: Staicu Mary L , Murphy Ian , Laguio-Vila Maryrose R
Published: January 2021

Background

Ampicillin/sulbactam is a recommended first-line agent for the treatment of aspiration pneumonia. Due to the ampicillin/sulbactam shortage, beginning in March 2019, alternative therapies, such as ceftriaxone plus metronidazole, have been utilized more frequently. The objective of this study is to examine clinical outcomes in adult inpatients treated with either ampicillin/sulbactam or ceftriaxone/metronidazole for aspiration pneumonia.

Methods

An electronic health record report identified patients ≥18 years of age that received ampicillin/sulbactam (pre-March 2019) or ceftriaxone/metronidazole (post-March 2019) with the indication of aspiration pneumonia. The primary objective was to describe 30-day all-cause readmission rates for patients that received ampicillin/sulbactam compared to ceftriaxone/metronidazole. The secondary objectives included hospital length of stay (LOS), 30-day all-cause mortality, C.difficile infection (CDI) within 3 months, and total antibiotic costs.

Results

A total of 86 patients (50 received ampicillin/sulbactam and 36 received ceftriaxone/ metronidazole) were included. Demographics were similar between groups. There was no significant difference in 30-day all-cause readmission rates (30% vs 19%, p=0.322). The ampicillin/sulbactam group, however, was found to have a significantly higher rate of 30-day all-cause mortality (12% vs 0%, p=0.038). Additionally, total duration of therapy was found to be significantly shorter in the ampicillin/sulbactam group (5 vs 7 days, p=0.002) with reduced overall cost of therapy($130 vs $235, p< 0.001). No differences were observed in hospital LOS or CDI within 3 months.

Conclusion

No difference was observed in 30-day all-cause readmissions in patients receiving ampicillin/sulbactam compared to ceftriaxone/metronidazole for the treatment of aspiration pneumonia. Further analyses are recommended to evaluate the impact on 30-day all-cause mortality.

Disclosures

All Authors: No reported disclosures
1462. The protective effect of pneumococcal vaccination on cardiovascular disease in adults: A systematic review and meta-analysis
Authors: Marra Fawziah , Zhang Angel , Gillman Emma , Bessai Katherine , Parhar Kamalpreet , Vadlamudi Nirma Khatri
Published: January 2021

Background

Epidemiological studies suggest a link between pneumococcal infection and an adverse cardiovascular outcome such as myocardial infarction. Therefore, studies have evaluated the protective effect of the 23-valent polysaccharide pneumococcal vaccination (PPV23), but results have varied. We conducted a meta-analysis to summarize the available evidence on the impact of PPV23 on cardiovascular disease

Methods

A literature search from January 1946 to September 2019 was conducted in Embase, Medline and Cochrane. All studies evaluating PPV23 compared to a control (placebo, no vaccine or another vaccine) for any cardiovascular events including myocardial infarction (MI), heart failure, cerebrovascular events were included. Risk ratios (RRs) were pooled using random effects models.

Results

Eighteen studies were included, with a total of 716,108 participants. Vaccination with PPV23 was associated with decreased risk of any cardiovascular event (RR: 0.91;95% CI: 0.84-0.99), and MI (RR of 0.88; 95% CI:0.79-0.98) in all age groups, with a significant effect in those 65 years and older, but not in the younger age group. Similarly, PPV23 vaccine was associated with significant risk reduction in all-cause mortality in all ages (RR: 0.78; 95%CI: 0.68-0.88), specifically in those aged 65 years and older (RR: 0.71; 95%CI: 0.60-0.84). A significant risk reduction in cerebrovascular disease was not observed following pneumococcal vaccination.

Conclusion

Polysaccharide pneumococcal vaccination decreases the risk of a cardiovascular event, specifically acute MI in the vaccinated population, particularly those 65 years of age and older. It would be highly beneficial to vaccinate the population who is at greater risk for cardiovascular diseases.

Disclosures

Fawziah Marra, BSc (Pharm), PharmD, Pfizer Inc (Research Grant or Support) Nirma Khatri Vadlamudi, BA, BS, MPH, Pfizer Inc (Research Grant or Support)