bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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 &gt; 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

Abstract

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&lt; 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

Abstract

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

Abstract

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&lt; 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

Abstract

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 &gt; 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

Abstract

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

Abstract

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 &lt;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)