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Polymyxin

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https://www.readbyqxmd.com/read/28526864/a-broad-spectrum-bactericidal-lipopeptide-with-anti-biofilm-properties
#1
Ohad Meir, Fadia Zaknoon, Uri Cogan, Amram Mor
Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526567/synergistic-effects-of-polymyxin-and-ionic-liquids-on-lipid-vesicle-membrane-stability-and-aggregation
#2
Sylvia L Hanna, Jenny L Huang, Alana J Swinton, Gregory A Caputo, Timothy D Vaden
Ionic liquids (ILs) have been investigated for potential antibacterial and antibiotic applications due to their ability to destabilize and permeabilize the lipid bilayers in cell membranes. Bacterial assays have shown that combining ILs with antibiotics can provide a synergistic enhancement of their antibacterial activities. We have characterized the mechanism by which the conventional ILs 1-butyl-3-methylimidazolium chloride (BMICl) and 1-butyl-3-methylimidazolium tetrafluoroborate (BMIBF4) enhance the lipid membrane permeabilization of the well-known antibiotic polymyxin B (PMB)...
May 11, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28505268/pharmacodynamics-of-dose-escalated-front-loading-polymyxin-b-regimens-against-polymyxin-resistant-mcr-1-harbouring-escherichia-coli
#3
Nicholas M Smith, Zackery P Bulman, Arthur O Sieron, Jürgen B Bulitta, Patricia N Holden, Roger L Nation, Jian Li, Gerard D Wright, Brian T Tsuji
Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance. Methods: A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days...
May 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28501124/effects-of-endotoxin-absorber-hemoperfusion-on-microcirculation-in-septic-pigs
#4
Yu-Chang Yeh, Linda Chia-Hui Yu, Chun-Yu Wu, Ya-Jung Cheng, Chen-Tse Lee, Wei-Zen Sun, Jui-Chang Tsai, Tzu-Yu Lin
BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations...
May 1, 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28497462/skin-hyperpigmentation-following-intravenous-polymyxin-b-treatment-associated-with-melanocyte-activation-and-inflammatory-process
#5
K P H Mattos, M L Cintra, I R Gouvêa, L Á Ferreira, P E N F Velho, P Moriel
What is known and objective Polymyxins were widely used until the 1960s; however, they fell into disfavour owing to their toxicity. The subsequent growth of infections caused by multidrug-resistant Gram-negative bacteria has led to renewed use of this class of antimicrobials in clinical practice. Acquired skin hyperpigmentation (SH) following intravenous polymyxin B treatment has been previously reported, but little is known about its pathogenesis, clinical course and treatment. To improve understanding of these issues, we conducted a prospective study of adult patients receiving intravenous polymyxin B treatment...
May 11, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28489424/a-novel-ph-responsive-hydrogel-based-on-calcium-alginate-engineered-by-the-previous-formation-of-polyelectrolyte-complexes-pecs-intended-to-vaginal-administration
#6
Natália Noronha Ferreira, Taciane Alvarenga Perez, Liliane Neves Pedreiro, Fabíola Garavello Prezotti, Fernanda Isadora Boni, Valéria Maria de Oliveira Cardoso, Tiago Venâncio, Maria Palmira Daflon Gremião
This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4...
May 10, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28487432/deciphering-mcr-2-colistin-resistance
#7
Jian Sun, Yongchang Xu, Rongsui Gao, Jingxia Lin, Wenhui Wei, Swaminath Srinivas, Defeng Li, Run-Shi Yang, Xing-Ping Li, Xiao-Ping Liao, Ya-Hong Liu, Youjun Feng
Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene, mcr-2, was revealed soon after the discovery of the paradigm gene mcr-1, which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28475585/acinetobacter-baumannii-strains-isolated-from-patients-in-intensive-care-units-in-goi%C3%A3-nia-brazil-molecular-and-drug-susceptibility-profiles
#8
Suellen Rocha Araújo Castilho, Cássia Silva de Miranda Godoy, Adriana Oliveira Guilarde, Juliana Lamaro Cardoso, Maria Cláudia Porfirio André, Ana Paula Junqueira-Kipnis, André Kipnis
Resistance to antimicrobial agents is increasing worldwide and imposes significant life-threatening risks to several different populations, especially those in intensive care units (ICUs). Bacteria can quickly develop or acquire resistance to antimicrobial drugs, and combined with their intrinsic potential to cause disease in humans, these bacteria can become deadly. Among Gram-negative bacteria, Acinetobacter baumannii is notorious as a frequent opportunistic pathogen associated with critically ill patients, and understanding the genetic basis of A...
2017: PloS One
https://www.readbyqxmd.com/read/28470018/use-of-carbapenems-polymyxins-and-tigecycline-in-united-states-children-s-hospitals-2010-2014
#9
Kathleen Chiotos, Rachael K Ross, Jennifer H Han, Matthew Miller, Jeffrey S Gerber
We characterized use of the carbapenems, polymyxins, and tigecycline in United States children's hospitals between 2010 and 2014. We found substantial variability in use across hospitals and overall decreased use over time. Most polymyxin and tigecycline use occurred in cystic fibrosis patients, and appendectomy was a common indication for carbapenem therapy.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28467187/evaluation-of-two-standard-and-two-chromogenic-selective-media-for-optimal-growth-and-enumeration-of-isolates-of-16-unique-bacillus-species
#10
M Shahjahan Kabir, Ying-Hsin Hsieh, Steven Simpson, Khalil Kerdahi, Irshad M Sulaiman
The genus Bacillus is a group of gram-positive endospore-forming bacteria that can cause food poisoning and diarrheal illness in humans. A wide range of food products have been linked to foodborne outbreaks associated with these opportunistic pathogens. The U.S. Food and Drug Administration recommends (in their Bacteriological Analytical Manual) the use of Bacara or mannitol egg yolk polymyxin (MYP) agar plates and the most-probable-number (MPN) method for enumeration and confirmation of Bacillus cereus and related species isolated from foods, sporadic cases, outbreaks, and routine environmental surveillance samples...
May 3, 2017: Journal of Food Protection
https://www.readbyqxmd.com/read/28463513/characterization-of-the-polymyxin-d-synthetase-biosynthetic-cluster-and-product-profile-of-paenibacillus-polymyxa-atcc-10401
#11
Charles A Galea, Meiling Han, Yan Zhu, Kade Roberts, Jiping Wang, Philip E Thompson, Jian L, Tony Velkov
The increasing prevalence of polymyxin-resistant bacteria has stimulated the search for improved polymyxin lipopeptides. Here we describe the sequence and product profile for polymyxin D nonribosomal peptide synthetase from Paenibacillus polymyxa ATCC 10401. The polymyxin D synthase gene cluster comprised five genes that encoded ABC transporters (pmxC and pmxD) and enzymes responsible for the biosynthesis of polymyxin D (pmxA, pmxB, and pmxE). Unlike polymyxins B and E, polymyxin D contains d-Ser at position 3 as opposed to l-α,γ-diaminobutyric acid and has an l-Thr at position 7 rather than l-Leu...
May 2, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28461268/formulation-and-characterisation-of-dissolving-microneedles-for-the-transdermal-delivery-of-therapeutic-peptides
#12
Colin Dillon, Helen Hughes, Niall J O'Reilly, Peter McLoughlin
The highly effective barrier properties of the stratum corneum (SC) limit the application of transdermal delivery to relatively small, lipophilic molecules. Microneedles (MNs) however, offer a route to effectively deliver a wide range of pharmaceuticals through the skin, bypassing the SC in a non-invasive and pain-free manner. This study presents a dissolving MN system composed of polyvinylpyrrolidone (PVP) and trehalose to encapsulate active pharmaceutical peptides within the MN matrix. Rapid systemic delivery is then achieved once the needles have penetrated the SC and dissolved in the interstitial fluid of the skin...
April 28, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28459130/identification-and-characterization-of-multifunctional-cationic-and-amphipathic-peptides-from-soybean-proteins
#13
Masayuki Taniguchi, Kengo Saito, Takafumi Nomoto, Toshiki Namae, Akihito Ochiai, Eiichi Saitoh, Takaaki Tanaka
In the present study, we identified and chemically synthesized three cationic and amphipathic peptides (Glycinin-17, BCAS-16, and BCBS-11) from soybean proteins. These peptides had high isoelectric points, high positive net charges, and included multiple hydrophobic amino acids. Subsequently, we identified multiple functions of these peptides, including antimicrobial, lipopolysaccharide-neutralizing, and angiogenic activities, and examined their cytotoxic activities against mammalian red blood cells. Glycinin-17, BCAS-16, and BCBS-11 exhibited antimicrobial activity against Porphyromonas gingivalis and Candida albicans whereas Glycinin-17 did not possess antimicrobial effects on Propionibacterium acnes and Streptococcus mutans...
April 29, 2017: Biopolymers
https://www.readbyqxmd.com/read/28458051/emergence-and-nosocomial-spread-of-carbapenem-resistant-oxa-232-producing-klebsiella-pneumoniae-in-brunei-darussalam
#14
Muhd Haziq Fikry Abdul Momin, Apostolos Liakopoulos, Lynette M Phee, David W Wareham
OBJECTIVES: Carbapenem-resistant Enterobacteriaceae (CRE) are identified as a major global health concern. The success of CRE is facilitated by the emergence, acquisition and spread of successful clones carrying plasmid-encoded resistance genes. In this study, an outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients hospitalised in Brunei Darussalam was investigated. METHODS: Over a 3-month period (May-July 2015), five multidrug-resistant K...
April 27, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28457834/a-network-perspective-on-antimicrobial-peptide-combination-therapies-the-potential-of-colistin-polymyxin-b-and-nisin
#15
REVIEW
Paula Jorge, Martín Pérez-Pérez, Gael Pérez Rodríguez, Maria Olívia Pereira, Anália Lourenço
Antimicrobial combinations involving antimicrobial peptides (AMPs) attract considerable attention within current antimicrobial and anti-resistance research. The objective of this study was to review the available scientific literature on the effects of antimicrobial combinations involving colistin (polymyxin E), polymyxin B and nisin, which are US Food and Drug Administration (FDA)-approved AMPs broadly tested against prominent multidrug-resistant pathogens. A bioinformatics approach based on literature mining and manual expert curation supported the reconstruction of experimental evidence on the potential of these AMP combinations, as described in the literature...
April 27, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28457352/carbapenem-resistant-enterobacteriaceae
#16
REVIEW
Alina Iovleva, Yohei Doi
Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a major threat. Commonly used antibiotics are generally inactive against CRE. Therefore, timely detection of CRE is of paramount importance. Among CRE, those producing carbapenem-hydrolyzing β-lactamase enzymes (carbapenemase-producing Enterobacteriaceae) are particularly of concern because they tend to spread, and treatment is difficult. The carbapenemase groups most commonly encountered include KPC, NDM, and OXA-48. Treatment options are limited and include combinations of polymyxins, tigecycline, aminoglycosides, or carbapenems; newer agents with activity against CRE and better safety profiles are becoming available and will likely emerge as the preferred therapy...
June 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28457027/changing-antimicrobial-resistance-pattern-of-isolates-from-an-icu-over-a-3-year-period
#17
Zarine Khety, Guruparasad Mohanta, Sachin Jain, Sameer Dawoodi
OBJECTIVE: To study the changing patterns of antimicrobial resistance in gram negative bacilli esp. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa species and Gram positive Staphylococcus aureus isolates from a 37 bedded ICU of a private hospital. METHODS: Antibiotic susceptibilities were determined by using disk diffusion and Vitek-2 system. RESULTS: A total of 13410 clinical samples were screened over a period of 3 years, among which 16...
February 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28455613/polymyxin-b-inhibits-the-chaperone-activity-of-plasmodium-falciparum-hsp70
#18
Tawanda Zininga, Ofentse J Pooe, Pertunia B Makhado, Lebogang Ramatsui, Earl Prinsloo, Ikechukwu Achilonu, Heinrich Dirr, Addmore Shonhai
Heat shock protein 70 (Hsp70) is a molecular chaperone that plays an important role in cellular proteostasis. Hsp70s are also implicated in the survival and pathogenicity of malaria parasites. The main agent of malaria, Plasmodium falciparum, expresses six Hsp70s. Of these, two (PfHsp70-1 and PfHsp70-z) localize to the parasite cytosol. Previously conducted gene knockout studies suggested that PfHsp70-z is essential, and it has been demonstrated that small-molecule inhibitors targeting PfHsp70-1 cause parasite death...
April 28, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28454673/synthesis-of-octapeptin-c4-and-biological-profiling-against-ndm-1-and-polymyxin-resistant-bacteria
#19
Bernd Becker, Mark S Butler, Karl A Hansford, Alejandra Gallardo-Godoy, Alysha G Elliott, Johnny X Huang, David J Edwards, Mark A T Blaskovich, Matthew A Cooper
The first synthesis of octapeptin C4 was achieved using a combination of solid phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram-negative bacteria, with moderate activity against Staphylococcus aureus. The linear analogue of octapeptin C4 was also prepared, which showed reduced activity.
April 12, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28445237/effects-of-polymyxin-b-hemoperfusion-on-mortality-in-patients-with-severe-sepsis-and-septic-shock-a-systemic-review-meta-analysis-update-and-disease-severity-subgroup-meta-analysis
#20
Tzu Chang, Yu-Kang Tu, Chen-Tse Lee, Anne Chao, Chi-Hsiang Huang, Ming-Jiuh Wang, Yu-Chang Yeh
OBJECTIVE: Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched from inception to May 2016...
April 25, 2017: Critical Care Medicine
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