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https://www.readbyqxmd.com/read/28458799/the-use-of-bloodstream-infection-mortality-to-measure-the-impact-of-antimicrobial-stewardship-interventions-assessing-the-evidence
#1
REVIEW
Sonali Coulter, Jason A Roberts, Krispin Hajkowicz, Kate Halton
This review sets out to evaluate the current evidence on the impact of inappropriate therapy on bloodstream infections (BSI) and associated mortality. Based on the premise that better prescribing practices should result in better patient outcomes, BSI mortality may be a useful metric to evaluate antimicrobial stewardship (AMS) interventions. A systematic search was performed in key medical databases to identify papers published in English between 2005 and 2015 that examined the association between inappropriate prescribing and BSI mortality in adult patients...
March 30, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/28448954/copper-complexes-containing-thiosemicarbazones-derived-from-6-nitropiperonal-antimicrobial-and-biophysical-properties
#2
Floyd A Beckford, Kelsey R Webb
A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49-7.50)×10(4)M(-1). In relation to HSA, the complexes interact strongly with binding constants on the order of 10(5)M(-1). The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals...
April 20, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28399424/resistance-among-gram-negative-eskape-pathogens-isolated-from-hospitalized-patients-with-intra-abdominal-and-urinary-tract-infections-in-latin-american-countries-smart-2013-2015
#3
James A Karlowsky, Daryl J Hoban, Meredith A Hackel, Sibylle H Lob, Daniel F Sahm
Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology...
April 8, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28373195/structural-modification-of-lipopolysaccharide-conferred-by-mcr-1-in-gram-negative-eskape-pathogens
#4
Yi-Yun Liu, Courtney E Chandler, Lisa M Leung, Christi L McElheny, Roberta T Mettus, Robert M Q Shanks, Jian-Hua Liu, David R Goodlett, Robert K Ernst, Yohei Doi
mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceae. mcr-1 encodes a phosphoethanolamine transferase and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli Here, we investigated the effect of mcr-1 on colistin susceptibility and lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE pathogens, which are often treated by colistin clinically...
April 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28343384/n6-n6-and-o4-modifications-to-neomycin-affect-ribosomal-selectivity-without-compromising-antibacterial-activity
#5
Girish C Sati, Dimitri Shcherbakov, Sven N Hobbie, Andrea Vasella, Erik C Böttger, David Crich
The synthesis of a series of neomycin derivatives carrying the 2-hydroxyethyl substituent on N6' and/or N6‴ both alone and in combination with a 4'-O-ethyl group is described. By means of cell-free translation assays with wild-type bacterial ribosomes and their hybrids with eukaryotic decoding A sites, we investigate how individual substituents and their combinations affect activity and selectivity at the target level. In principle, and as shown by cell-free translation assays, modifications of the N6' and N6‴ positions allow enhancement of target selectivity without compromising antibacterial activity...
May 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28335205/photosensitizer-embedded-polyacrylonitrile-nanofibers-as-antimicrobial-non-woven-textile
#6
Sarah L Stanley, Frank Scholle, Jiadeng Zhu, Yao Lu, Xiangwu Zhang, Xingci Situ, Reza A Ghiladi
Toward the objective of developing platform technologies for anti-infective materials based upon photodynamic inactivation, we employed electrospinning to prepare a non-woven textile comprised of polyacrylonitrile nanofibers embedded with a porphyrin-based cationic photosensitizer; termed PAN-Por((+)). Photosensitizer loading was determined to be 34.8 nmol/mg material; with thermostability to 300 °C. Antibacterial efficacy was evaluated against four bacteria belonging to the ESKAPE family of pathogens (Staphylococcus aureus; vancomycin-resistant Enterococcus faecium; Acinetobacter baumannii; and Klebsiella pneumonia), as well as Escherichia coli...
April 20, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28320716/in-vitro-activity-of-imipenem-relebactam-against-gram-negative-eskape-pathogens-isolated-by-clinical-laboratories-in-the-united-states-in-2015-results-from-the-smart-global-surveillance-program
#7
Sibylle H Lob, Meredith A Hackel, Krystyna M Kazmierczak, Katherine Young, Mary R Motyl, James A Karlowsky, Daniel F Sahm
Relebactam (formerly MK-7655) is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC), and is currently in clinical development in combination with imipenem/cilastatin. Using Clinical and Laboratory Standards Institute (CLSI) defined broth microdilution methodology, we evaluated the in vitro activities of imipenem-relebactam, imipenem, and seven routinely tested parenteral antimicrobial agents against gram-negative ESKAPE pathogens (Pseudomonas aeruginosa, n = 845; Klebsiella pneumoniae, n = 689; Enterobacter spp...
March 20, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28291947/evaluating-the-effect-of-peptoid-lipophilicity-on-antimicrobial-potency-cytotoxicity-and-combinatorial-library-design
#8
Jeremy A Turkett, Kevin L Bicker
Growing prevalence of antibiotic resistant bacterial infections necessitates novel antimicrobials, which could be rapidly identified from combinatorial libraries. We report the use of the peptoid library agar diffusion (PLAD) assay to screen peptoid libraries against the ESKAPE pathogens, including the optimization of assay conditions for each pathogen. Work presented here focuses on the tailoring of combinatorial peptoid library design through a detailed study of how peptoid lipophilicity relates to antibacterial potency and mammalian cell toxicity...
April 10, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28261570/human-salivary-protein-histatin-5-has-potent-bactericidal-activity-against-eskape-pathogens
#9
Han Du, Sumant Puri, Andrew McCall, Hannah L Norris, Thomas Russo, Mira Edgerton
ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter species) pathogens have characteristic multiple-drug resistance and cause an increasing number of nosocomial infections worldwide. Peptide-based therapeutics to treat ESKAPE infections might be an alternative to conventional antibiotics. Histatin 5 (Hst 5) is a salivary cationic histidine-rich peptide produced only in humans and higher primates. It has high antifungal activity against Candida albicans through an energy-dependent, non-lytic process; but its bactericidal effects are less known...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28242720/fluorescence-high-throughput-screening-for-inhibitors-of-tonb-action
#10
Brittany L Nairn, Olivia S Eliasson, Dallas R Hyder, Noah J Long, Aritri Majumdar, Somnath Chakravorty, Peter McDonald, Anuradha Roy, Salete M Newton, Phillip E Klebba
Gram-negative bacteria acquire ferric siderophores through TonB-dependent outer membrane transporters (TBDT). By fluorescence spectroscopic hgh-throughput screening (FLHTS), we identified inhibitors of TonB-dependent ferric enterobactin (FeEnt) uptake through Escherichia coli FepA (EcoFepA). Among 165 inhibitors found in a primary screen of 17,441 compounds, we evaluated 20 in secondary tests: TonB-dependent ferric siderophore uptake and colicin killing and proton motive force-dependent lactose transport. Six of 20 primary hits inhibited TonB-dependent activity in all tests...
May 15, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28190396/in-vitro-screening-of-an-fda-approved-library-against-eskape-pathogens
#11
Waleed Younis, Ahmed AbdelKhalek, Abdelrahman S Mayhoub, Mohamed N Seleem
Bacterial resistance to conventional antibiotics is an increasingly serious threat to public health worldwide that requires immediate exploration and the development of novel antimicrobial compounds. Drug repurposing is an inexpensive and untapped source of new antimicrobial leads, and it holds many attractive features warranting further attention for antimicrobial drug discovery. In an effort to repurpose drugs and explore new leads in the field of antimicrobial drug discovery, we performed a whole-cell screening assay of 1,600 Food and Drug Administration (FDA) approved drugs against Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (ESKAPE) pathogens...
February 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28165020/a-potent-synthetic-inorganic-antibiotic-with-activity-against-drug-resistant-pathogens
#12
Shelby Hubick, Arumugam Jayaraman, Alexander McKeen, Shelby Reid, Jane Alcorn, John Stavrinides, Brian T Sterenberg
The acronymously named "ESKAPE" pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to "eskape" antibiotic treatment. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE)...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28132897/targeting-biofilms-and-persisters-of-eskape-pathogens-with-p14kans-a-kanamycin-peptide-conjugate
#13
Mohamed F Mohamed, Anna Brezden, Haroon Mohammad, Jean Chmielewski, Mohamed N Seleem
BACKGROUND: The worldwide emergence of antibiotic resistance represents a serious medical threat. The ability of these resistant pathogens to form biofilms that are highly tolerant to antibiotics further aggravates the situation and leads to recurring infections. Thus, new therapeutic approaches that adopt novel mechanisms of action are urgently needed. To address this significant problem, we conjugated the antibiotic kanamycin with a novel antimicrobial peptide (P14LRR) to develop a kanamycin peptide conjugate (P14KanS)...
April 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28051952/antimicrobial-susceptibility-of-gram-negative-eskape-pathogens-isolated-from-hospitalized-patients-with-intra-abdominal-and-urinary-tract-infections-in-asia-pacific-countries-smart-2013-2015
#14
James A Karlowsky, Daryl J Hoban, Meredith A Hackel, Sibylle H Lob, Daniel F Sahm
Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) are responsible for increases in antimicrobial-resistant infections worldwide. We determined in vitro susceptibilities to eight parenteral antimicrobial agents using Clinical and Laboratory Standards Institute broth microdilution methodology for Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal infections (IAIs) (n=3052) and urinary tract infections (UTIs) (n=1088) in 11 Asia-Pacific countries/regions from 2013 to 2015...
January 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27986722/detection-of-eskape-bacterial-pathogens-at-the-point-of-care-using-isothermal-dna-based-assays-in-a-portable-degas-actuated-microfluidic-diagnostic-assay-platform
#15
Lars D Renner, Jindong Zan, Linda I Hu, Manuel Martinez, Pedro J Resto, Adam C Siegel, Clint Torres, Sara B Hall, Tom R Slezak, Tuan H Nguyen, Douglas B Weibel
An estimated 1.5 billion microbial infections occur globally each year and result in ∼4.6 million deaths. A technology gap associated with commercially available diagnostic tests in remote and underdeveloped regions prevents timely pathogen identification for effective antibiotic chemotherapies for infected patients. The result is a trial-and-error approach that is limited in effectiveness, increases risk for patients while contributing to antimicrobial drug resistance, and reduces the lifetime of antibiotics...
February 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27933975/high-antibacterial-activity-of-functionalized-chemically-exfoliated-mos2
#16
Subhendu Pandit, Subbaraj Karunakaran, Sunil Kumar Boda, Bikramjit Basu, Mrinmoy De
In view of the implications of inherent resistance of pathogenic bacteria, especially ESKAPE pathogens toward most of the commercially available antibiotics and the importance of these bacteria-induced biofilm formation leading to chronic infection, it is important to develop new-generation synthetic materials with greater efficacy toward antibacterial property. In addressing this issue, this paper reports a proof-of-principle study to evaluate the potential of functionalized two-dimensional chemically exfoliated MoS2 (ce-MoS2) toward inhibitory and bactericidal property against two representative ESKAPE pathogenic strain-a Gram-positive Staphylococcus aureus (MRSA) and a Gram-negative Pseudomonas aeruginosa...
November 23, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27820797/non-classical-transpeptidases-yield-insight-into-new-antibacterials
#17
Pankaj Kumar, Amit Kaushik, Evan P Lloyd, Shao-Gang Li, Rohini Mattoo, Nicole C Ammerman, Drew T Bell, Alexander L Perryman, Trevor A Zandi, Sean Ekins, Stephan L Ginell, Craig A Townsend, Joel S Freundlich, Gyanu Lamichhane
Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the β-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of β-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for β-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria...
January 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/27756563/allicin-inspired-thiolated-fluoroquinolones-as-antibacterials-against-eskape-pathogens
#18
Jordan G Sheppard, Timothy E Long
Thiolated fluoroquinolones were synthesized from ciprofloxacin and evaluated for antimicrobial activity against a panel of pathogenic bacteria. Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA) exhibited the highest level of increased sensitivity toward ciprofloxacin bound with a N-propylthio substituent. Evidence was found that the antibiotics form disulfides with low molecular weight thiols in bacteria and potentiate generation of cytosolic reactive oxygen species (ROS). In final analysis, the enhanced anti-MRSA activity of thiolated fluoroquinolones was attributed to increased cell permeability and reaction with cytosolic thiols that yields an inactive disulfide metabolite and the parent drug ciprofloxacin as an inhibitor of DNA synthesis...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27620956/antibiotic-resistance-in-burkholderia-species
#19
Katherine A Rhodes, Herbert P Schweizer
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients...
September 2016: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/27617798/combating-multidrug-resistant-gram-negative-bacteria-with-structurally-nanoengineered-antimicrobial-peptide-polymers
#20
Shu J Lam, Neil M O'Brien-Simpson, Namfon Pantarat, Adrian Sulistio, Edgar H H Wong, Yu-Yen Chen, Jason C Lenzo, James A Holden, Anton Blencowe, Eric C Reynolds, Greg G Qiao
With the recent emergence of reports on resistant Gram-negative 'superbugs', infections caused by multidrug-resistant (MDR) Gram-negative bacteria have been named as one of the most urgent global health threats due to the lack of effective and biocompatible drugs. Here, we show that a class of antimicrobial agents, termed 'structurally nanoengineered antimicrobial peptide polymers' (SNAPPs) exhibit sub-μM activity against all Gram-negative bacteria tested, including ESKAPE and colistin-resistant and MDR (CMDR) pathogens, while demonstrating low toxicity...
September 12, 2016: Nature Microbiology
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