The Experts below are selected from a list of 14487 Experts worldwide ranked by ideXlab platform
Wei Zheng - One of the best experts on this subject based on the ideXlab platform.
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Current Antimicrobial Susceptibility Testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new Antimicrobial Susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical Antimicrobial Susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.
Wei Sun - One of the best experts on this subject based on the ideXlab platform.
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Current Antimicrobial Susceptibility Testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new Antimicrobial Susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical Antimicrobial Susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.
Romney M Humphries - One of the best experts on this subject based on the ideXlab platform.
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verification is an integral part of Antimicrobial Susceptibility Test quality assurance
Journal of Clinical Microbiology, 2020Co-Authors: Romney M Humphries, Patricia J SimnerAbstract:With interest we read the commentary of Kirby and colleagues, which advocated implementing Antimicrobial Susceptibility Testing (AST) for new drugs without verification ([1][1]). We agree with the authors that new drugs should not be used clinically without an accompanying AST. Implementing AST for
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impact of 21st century cures act on breakpoints and commercial Antimicrobial Susceptibility Test systems progress and pitfalls
Journal of Clinical Microbiology, 2018Co-Authors: Romney M Humphries, Mary Jane Ferraro, Janet A HindlerAbstract:Antimicrobial resistance is the most pressing medical challenge of the past decade. At the front line are clinical laboratories, which are responsible for accurately reporting Antimicrobial Susceptibility Test (AST) results to clinicians and public health authorities. The ability of the laboratory to detect resistance has been hampered by several factors. In 2016, the 21st Century Cures Act was signed into law, marking an important step toward resolving many regulatory dilemmas that hampered development and updates to commercial AST systems (cASTs). We describe the pathway and history of U.S. regulation of cASTs and outline both the rewards and unmet needs possible from the 21st Century Cures Act.
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performance of vitek 2 for Antimicrobial Susceptibility Testing of enterobacteriaceae with vitek 2 2009 fda and 2014 clsi breakpoints
Journal of Clinical Microbiology, 2015Co-Authors: April M Bobenchik, Janet A Hindler, Eszter Deak, Carmen L Charlton, Romney M HumphriesAbstract:ABSTRACT Vitek 2 (bioMerieux Inc., Durham, NC) is a widely used commercial Antimicrobial Susceptibility Test system. We compared the MIC results obtained using the Vitek 2 AST-GN69 and AST-XN06 cards to those obtained by CLSI broth microdilution (BMD) for 255 isolates of Enterobacteriaceae, including 25 isolates of carbapenem-resistant Enterobacteriaceae. In total, 25 Antimicrobial agents were examined. For 10 agents, the MIC data were evaluated using two sets of breakpoints: (i) the Vitek 2 breakpoints, which utilized the 2009 FDA breakpoints at the time of the study and are equivalent to the 2009 CLSI M100-S19 breakpoints, and (ii) the 2014 CLSI M100-S24 breakpoints. There was an overall 98.7% essential agreement (EA). The categorical agreement was 95.5% (CA) using the Vitek 2 breakpoints and 95.7% using the CLSI breakpoints. There was 1 very major error (VME) (0.05%) observed using the Vitek 2 breakpoints (cefazolin) and 8 VMEs (0.5%) using the CLSI breakpoints (2 each for aztreonam, cefepime, and ceftriaxone, and 1 for cefazolin and ceftazidime). Fifteen major errors (MEs) (0.4%) were noted using the Vitek 2 breakpoints and 8 (0.5%) using the CLSI breakpoints. Overall, the Vitek 2 performance was comparable to that of BMD for Testing a limited number of Enterobacteriaceae commonly isolated by clinical laboratories. Ongoing studies are warranted to assess performance in isolates with emerging resistance.
Ronald N Jones - One of the best experts on this subject based on the ideXlab platform.
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reanalysis of cefazolin surrogate Susceptibility breakpoints utilized as guidances for oral cephalosporin treatments of uncomplicated urinary tract infections caution concerning application to cefadroxil
Diagnostic Microbiology and Infectious Disease, 2020Co-Authors: Hien M Nguyen, Ronald N JonesAbstract:Based on Antimicrobial Susceptibility Test interpretive breakpoint criteria from Clinical and Laboratory Standards Institute and United States Committee on Antimicrobial Susceptibility Testing, cefazolin uncomplicated urinary tract infection (uUTI) surrogate breakpoints do not accurately predict cefadroxil or cephradine Susceptibility when Testing indicated Enterobacteriaceae species isolates. Hence, these two orally-administered cephalosporins (OC) are not equivalent spectrum substitutes for cephalexin or six other related OC agents for contemporary uUTI therapy.
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old in vitro Antimicrobial breakpoints are misleading stewardship efforts delaying adoption of innovative therapies and harming patients
Open Forum Infectious Diseases, 2020Co-Authors: Paul G Ambrose, Sujata M Bhavnani, David R Andes, John S Bradley, Robert K Flamm, Jason M Pogue, Ronald N JonesAbstract:The current Antimicrobial market and old (pre-2000) in vitro Antimicrobial Susceptibility Test interpretative criteria (STIC) are not working properly. Malfunctioning Susceptibility breakpoints and Antimicrobial markets have serious implications for both patients (ie, from a safety and efficacy perspective) and antibiotic-focused pharmaceutical and biotechnology company economic viability. Poorly functioning STIC fail both patients and clinicians since they do not discriminate between likely effective and ineffective Antimicrobial regimens. Poor economic viability fails patients and clinicians as it decreases the industry's ability to develop Antimicrobial agents that clinicians and patients urgently require now and in the future. Herein, we review how STIC for older Antimicrobial agents were determined and how their correction can impact the perceived utility of old relative to new Antimicrobial agents. Moreover, we describe the data and analysis needs to systematically reevaluate older STIC values. We call for professional infectious diseases societies, government agencies, and other consensus bodies interested in the appropriate use of Antimicrobial agents to join an effort to systematically evaluate and, where warranted, correct STIC for all relevant Antimicrobial agents. This effort will amplify the effects of other measures designed to increase appropriate Antimicrobial use (ie, good Antimicrobial stewardship), development, and regulation.
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factors influencing broth microdilution Antimicrobial Susceptibility Test results for dalbavancin a new glycopeptide agent
Journal of Clinical Microbiology, 2007Co-Authors: Robert Rennie, Ronald N Jones, Laura M Koeth, Thomas R Fritsche, Cindy C Knapp, S B Killian, Beth P GoldsteinAbstract:Performance of Antimicrobial Susceptibility Tests with new agents requires careful consideration of the properties of the Antimicrobial to ensure that the Tests are standardized, reproducible, and reflect the true potency of the drug. Dalbavancin is a new glycopeptide with potent activity against gram-positive bacterial species. The investigations described here demonstrated that methodologic modifications of procedures are necessary to ensure consistent Test results, both for quality control and for routine Testing of clinical isolates. Dimethyl sulfoxide is the preferred primary solvent. The addition of 0.002% polysorbate-80 (a surfactant) to dalbavancin-containing wells in the reference broth microdilution assay resulted in consistent and reproducible MIC results for three quality control strains: Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, and Streptococcus pneumoniae ATCC 49619. The same degree of consistency was observed among clinical isolates of gram-positive bacterial species Tested in several clinical laboratories. These results indicate that the addition of 0.002% (final concentration) of the surfactant in broth microdilution Tests produces optimal dalbavancin MICs required for accurate and reproducible clinical laboratory Tests, without untoward influences of substrate binding or media constituents.
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vancomycin resistant enterococcus raffinosus molecular epidemiology species identification error and frequency of occurrence in a national resistance surveillance program
Diagnostic Microbiology and Infectious Disease, 1997Co-Authors: Werner W Wilke, Steven A Marshall, Stacy L Coffman, Michael A Pfaller, Michael B Edmund, Richard P Wenzel, Ronald N JonesAbstract:Enterococcal blood stream infections are the third most common among all nosocomial blood stream infections in the United States and the occurrence of glycopeptide (vancomycin, teicoplanin) resistance in these isolates has markedly increased. Control of hospital-acquired infections with vancomycin-resistant enterococci requires high quality Antimicrobial Susceptibility Test methods and species identification procedures as a supplement to epidemiologic investigation and appropriate infection control procedures. In this report, bacteremias caused by Enterococcus avium (BioMerieux Vitek, Hazelwood, MO, USA) were observed to be Enterococcus raffinosus infections (six of eight cases; 1.1% of all cases) when reference biochemical identification methods were applied. The vancomycin-susceptible E. raffinosis (two strains) and E. avium (two strains) had unique phenotypic and genotypic molecular profiles. In contrast, four vancomycin-resistant E. raffinosus strains (van A by polymerase chain reaction) from a single institution had the same phenotypic and molecular (PCR, PFGE, ribotyping) pattern, indicating clonal dissemination among four patients over a 66-day period. Clinical laboratories should be aware of the high probability that van A genes may be transferred from Enterococcus faecium or Enterococcus faecalis to other more rarely encountered Enterococcus species. Also contemporary, widely used commercial identification systems may fail to accurately identify those rare species. Errors appear to be most prevalent for E. avium, Enterococcus durans, and E. raffinosus based on the experience of the SCOPE Program.
Peter R Williamson - One of the best experts on this subject based on the ideXlab platform.
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria
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rapid Antimicrobial Susceptibility Test for identification of new therapeutics and drug combinations against multidrug resistant bacteria
Emerging microbes & infections, 2016Co-Authors: Wei Sun, Rebecca A Weingarten, Noel Southall, Sheng Dai, Paul Shinn, Philip E Sanderson, Peter R Williamson, Karen M Frank, Wei ZhengAbstract:Current Antimicrobial Susceptibility Testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new Antimicrobial Susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical Antimicrobial Susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.