scholarly journals Comparative Tn-Seq reveals common daptomycin resistance determinants in Staphylococcus aureus despite strain-dependent differences in essentiality of shared cell envelope genes

2019 ◽  
Author(s):  
Kathryn A. Coe ◽  
Wonsik Lee ◽  
Gloria Komazin-Meredith ◽  
Timothy C. Meredith ◽  
Yonatan H. Grad ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Cell Envelope ◽  
The United States ◽  
Resistance Mechanisms ◽  
Essential Genes ◽  
Next Generation ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Strain Dependent

AbstractAntibiotic-resistant Staphylococcus aureus remains a leading cause of antibiotic resistance-associated mortality in the United States. Given the reality of multi-drug resistant infections, it is imperative that we establish and maintain a pipeline of new compounds to replace or supplement our current antibiotics. A first step towards this goal is to prioritize targets by identifying the genes most consistently required for survival across the S. aureus phylogeny. Here we report the first direct comparison of gene essentiality across multiple strains of S. aureus via transposon sequencing. We show that mutant fitness varies by strain in key pathways, underscoring the importance of using more than one strain to differentiate between core and strain-dependent essential genes. Despite baseline differences in gene importance, several pathways, including the lipoteichoic acid pathway, become consistently essential under daptomycin exposure, suggesting core vulnerabilities that can be exploited to resensitize daptomycin-nonsusceptible isolates. We also demonstrate the merit of using transposons with outward-facing promoters capable of overexpressing nearby genes for identifying clinically-relevant gain-of-function resistance mechanisms. Together, the daptomycin vulnerabilities and resistance mechanisms support a mode of action with wide-ranging effects on the cell envelope and cell division. This work adds to a growing body of literature demonstrating the nuanced insights gained by comparing Tn-Seq results across multiple bacterial strains.Author summaryAntibiotic-resistant Staphylococcus aureus kills thousands of people every year in the United States alone. To stay ahead of the looming threat of multidrug-resistant infections, we must continue to develop new antibiotics and find ways of making our current repertoire of antibiotics more effective, including by finding pairs of compounds that perform best when administered together. In the age of next-generation sequencing, we can now use transposon sequencing to find potential targets for new antibiotics on a genome-wide scale, identified as either essential genes or genes that become essential in the presence of an antibiotic. In this work, we created a compendium of genes that are essential across a range of S. aureus strains, as well as those that are essential in the presence of the antibiotic daptomycin. The results will be a resource for researchers working to develop the next generation of antibiotic therapies.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

scholarly journals Five-Year Summary of In Vitro Activity and Resistance Mechanisms of Linezolid against Clinically Important Gram-Positive Cocci in the United States from the LEADER Surveillance Program (2011 to 2015)

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Michael A. Pfaller ◽  
Rodrigo E. Mendes ◽  
Jennifer M. Streit ◽  
Patricia A. Hogan ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Resistance Mechanisms ◽  
23S Rrna ◽  
Rrna Gene ◽  
Gram Positive ◽  
Content Type ◽  
Linezolid Resistance

ABSTRACT This report describes linezolid susceptibility testing results for 6,741 Gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the report summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity in testing against Staphylococcus aureus, inhibiting >99.9% of 3,031 isolates at ≤2 µg/ml. Similarly, linezolid showed coverage against 99.2% of coagulase-negative staphylococci, 99.7% of enterococci, and 100.0% of Streptococcus pneumoniae, virdans group, and beta-hemolytic streptococcus isolates tested. The overall linezolid resistance rate remained a modest <1% from 2011 to 2015. Staphylococci, especially Staphylococcus epidermidis, showed a range of linezolid resistance mechanisms. Increased annual trends for the presence of cfr among Staphylococcus aureus isolates were not observed, but 64.3% (9/14) of the isolates with decreased susceptibility (MIC, ≥4 µg/ml) to linezolid carried this transferrable gene (2011 to 2015). The cfr gene was detected in 21.9% (7/32) of linezolid-resistant staphylococci other than S. aureus from 2011 to 2015. The optrA gene was noted in half (2/4) of the population of linezolid-nonsusceptible Enterococcus faecalis isolates from 2011 to 2015, while linezolid-nonsusceptible Enterococcus faecium isolates showed alterations predominantly (16/16) in the 23S rRNA gene (G2576T). This report confirms a long record of linezolid activity against Gram-positive isolates in the United States since regulatory approval in 2000 and reports the oxazolidinones evolving resistance mechanisms.

THE NEW CURRICULUM STANDARDS FOR ASTRONOMY IN THE UNITED STATES

2015 ◽  
pp. 131-151
Author(s):  
Sharon P. Schleigh ◽  
Stephanie J. Slater ◽  
Timothy F. Slater ◽  
Debra J. Stork
Keyword(s):  
United States ◽  
The United States ◽  
Next Generation Science Standards ◽  
Next Generation ◽  
Curriculum Standards ◽  
Science Standards ◽  
New Curriculum

Há um grande interesse em restringir a ampla gama e vasto domínio dos possíveis temas que poderiam ser ensinados sobre astronomia em uma estrutura gerenciável. Embora não haja nenhum currículo nacional obrigatório nos Estados Unidos, uma análise dos três esforços nacionais recentes para criar uma sequência apropriada de conceitos de astronomia por idade para serem ensinados nas escolas primárias e secundárias revela uma considerável falta de consenso a respeito de quais conceitos são mais apropriados para cada idade e quais tópicos devem ser cobertos. O esquema de padronização mais recente para a educação científica dos EUA, o Next Generation Science Standards (Padrões em Ciência: Nova Geração), sugere que a maioria dos conceitos de astronomia devem ser ensinados apenas nos últimos anos de educação do aluno; e no entanto  foi recebido com críticas consideráveis. Uma comparação dos esquemas de aprendizagem da astronomia nos Estados Unidos e uma breve discussão das críticas levantadas podem proporcionar aos educadores de astronomia internacionais dados de comparação na formulação de recomendações em suas próprias regiões.

The Insidious Momentum of American Mass Incarceration

2020 ◽  
Author(s):  
Franklin E. Zimring
Keyword(s):  
United States ◽  
Public Policy ◽  
Twentieth Century ◽  
Mass Incarceration ◽  
The United States ◽  
Next Generation ◽  
Single Generation ◽  
American Life ◽  
Peak Rate ◽  
Or Practice

The phenomenal growth of penal confinement in the United States in the last quarter of the twentieth century is still a public policy mystery. Why did it happen when it happened? What explains the unprecedented magnitude of prison and jail expansion? Why are the current levels of penal confinement so very close to the all-time peak rate reached in 2007? What is the likely course of levels of penal confinement in the next generation of American life? Are there changes in government or policy that can avoid the prospect of mass incarceration as a chronic element of governance in the United States? This study is organized around four major concerns: What happened in the 33 years after 1973? Why did these extraordinary changes happen in that single generation? What is likely to happen to levels of penal confinement in the next three decades? What changes in law or practice might reduce this likely penal future?

scholarly journals The Effectiveness of Contact Precautions on Methicillin-Resistant Staphylococcus aureus in Long-term Care Across the United States

2019 ◽  
Vol 71 (7) ◽  
pp. 1676-1683 ◽  
Author(s):  
Daniel J Morgan ◽  
Min Zhan ◽  
Michihiko Goto ◽  
Carrie Franciscus ◽  
Bruce Alexander ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Long Term Care ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
The United States ◽  
Standard Precautions ◽  
Term Care ◽  
Contact Precautions ◽  
Care Facilities

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of health care–associated infections in long-term care facilities (LTCFs). The Centers for Disease Control and Prevention recommends contact precautions for the prevention of MRSA within acute care facilities, which are being used within the United States Department of Veterans Affairs (VA) for LTCFs in a modified fashion. The impact of contact precautions in long-term care is unknown. Methods To evaluate whether contact precautions decreased MRSA acquisition in LTCFs, compared to standard precautions, we performed a retrospective effectiveness study (pre-post, with concurrent controls) using data from the VA health-care system from 1 January 2011 until 31 December 2015, 2 years before and after a 2013 policy recommending a more aggressive form of contact precautions. Results Across 75 414 patient admissions from 74 long-term care facilities in the United States, the overall unadjusted rate of MRSA acquisition was 2.6/1000 patient days. Patients were no more likely to acquire MRSA if they were cared for using standard precautions versus contact precautions in a multivariable, discrete time survival analysis, controlling for patient demographics, risk factors, and year of admission (odds ratio, 0.97; 95% confidence interval, .85–1.12; P = .71). Conclusions MRSA acquisition and infections were not impacted by the use of active surveillance and contact precautions in LTCFs in the VA.

scholarly journals Epidemics of Community-Associated Methicillin-Resistant Staphylococcus aureus in the United States: A Meta-Analysis

PLoS ONE ◽  
2013 ◽  
Vol 8 (1) ◽  
pp. e52722 ◽  
Author(s):  
Vanja M. Dukic ◽  
Diane S. Lauderdale ◽  
Jocelyn Wilder ◽  
Robert S. Daum ◽  
Michael Z. David
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Meta Analysis ◽  
The United States ◽  
Methicillin Resistant

Activity of Oritavancin Against Gram-positive Pathogens Causing Bloodstream Infections in the United States Over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019)

2021 ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Helio S. Sader ◽  
Jennifer M. Streit ◽  
Mariana Castanheira ◽  
Rodrigo E. Mendes
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Bloodstream Infections ◽  
The United States ◽  
Drug Resistant ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Vancomycin Resistant ◽  
Over Time

Oritavancin displayed potent and stable activity (MIC 90 range, 0.06-0.5 mg/L) over time (2010-2019) against Gram-positive pathogens causing bloodstream infections, including methicillin-resistant Staphylococcus aureus and resistant subsets of Enterococcus spp. Daptomycin and linezolid were also active against methicillin-resistant S. aureus and vancomycin-resistant Enterococcus . Only oritavancin and linezolid remained active against Enterococcus faecium isolates displaying an elevated daptomycin MIC (i.e., 2-4 mg/L). Proportions of methicillin-resistant S. aureus and vancomycin-resistant Enterococcus within the respective S. aureus and enterococcal populations decreased over this period.

scholarly journals Corrected Genome Sequence of Acinetobacter baumannii Strain AB0057, an Antibiotic-Resistant Isolate from Lineage 1 of Global Clone 1

2017 ◽  
Vol 5 (35) ◽  
Author(s):  
Mohammad Hamidian ◽  
Pratap Venepally ◽  
Ruth M. Hall ◽  
Mark D. Adams
Keyword(s):  
United States ◽  
Acinetobacter Baumannii ◽  
Genome Sequence ◽  
The United States ◽  
Targeted Sequencing ◽  
Resistant Isolate ◽  
Illumina Hiseq ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Pcr Products

ABSTRACT Extensively antibiotic-resistant Acinetobacter baumannii isolate AB0057 recovered in the United States in 2004 was one of the first global clone 1 isolates to be completely sequenced. Here, the complete 4.05-Mb genome sequence (chromosome and one plasmid) has been revised using Illumina HiSeq data and targeted sequencing of PCR products.

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