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Polymyxin

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https://www.readbyqxmd.com/read/28103139/endotoxin-neutralization-by-an-o-antigen-specific-monoclonal-antibody-a-potential-novel-therapeutic-approach-against-klebsiella-pneumoniaest258
#1
Valéria Szijártó, Luis M Guachalla, Katharina Hartl, Cecília Varga, Adriana Badarau, Irina Mirkina, Zehra C Visram, Lukas Stulik, Christine A Power, Eszter Nagy, Gábor Nagy
Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases...
January 19, 2017: Virulence
https://www.readbyqxmd.com/read/28096166/the-role-of-renal-drug-exposure-in-polymyxin-b-induced-nephrotoxicity
#2
Pooja Manchandani, Jian Zhou, Jessica T Babic, Kimberly R Ledesma, Luan D Truong, Vincent H Tam
Despite dose-limiting nephrotoxic potentials, polymyxin B has re-emerged as the last line of therapy against multidrug-resistant Gram-negative bacterial infections. However, the handling of polymyxin B by the kidneys is still not thoroughly understood. The objectives of this study were to evaluate the impact of renal polymyxin B exposure on nephrotoxicity and to explore the role of megalin in renal drug accumulation. Sprague-Dawley rats (225-250 g) were divided into 3 dosing groups, and polymyxin B was administered (5 mg/kg, 10 mg/kg and 20 mg/kg) subcutaneously once daily...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28096154/influence-of-rhlr-and-lasr-on-polymyxin-pharmacodynamics-in-pseudomonas-aeruginosa-implications-for-quorum-sensing-inhibition-with-azithromycin
#3
Zackery P Bulman, Neang S Ly, Justin R Lenhard, Patricia N Holden, Jürgen B Bulitta, Brian T Tsuji
Quorum sensing's impact on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 and an isogenic rhlR/lasR double knockout. For polymyxin B, greater killing against the rhlR/lasR knockout versus PAO1 was observed at 10(8) CFU/mL(polymyxin B EC50:5.61 versus 12.5mg/L, respectively; p<0.005). Polymyxin B combined with azithromycin (256mg/L) was synergistic against each strain, significantly reducing the respective polymyxin B EC50 compared to monotherapy (p<0.005), and is a promising strategy to combat P...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28092497/polymyxin-b-hemoperfusion-for-sepsis-and-septic-shock-a-systematic-review-and-meta-analysis
#4
Takero Terayama, Kazuma Yamakawa, Yutaka Umemura, Morio Aihara, Satoshi Fujimi
BACKGROUND: To evaluate the efficacy and safety of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) therapy in patients with sepsis. DESIGN: A systematic review and meta-analysis of four major databases: Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, and Science Citation Index Expanded. STUDY SELECTION: Randomized controlled trials comparing PMX-DHP with conventional therapy on the outcome of mortality in patients with severe sepsis/septic shock...
January 16, 2017: Surgical Infections
https://www.readbyqxmd.com/read/28080060/pharmacokinetics-of-the-individual-major-components-of-polymyxin-b-and-colistin-in-rats
#5
Sivashangarie Sivanesan, Kade Roberts, Jiping Wang, Soon-Ee Chea, Philip E Thompson, Jian Li, Roger L Nation, Tony Velkov
The pharmacokinetics of polymyxin B1, polymyxin B2, colistin A, and colistin B were investigated in a rat model following intravenous administration (0.8 mg/kg) of each individual component. Plasma and urine concentrations were determined by LC-MS/MS, and plasma protein binding was measured by ultracentrifugation. Total and unbound pharmacokinetic parameters for each component were calculated using noncompartmental analysis. All of the polymyxin components had a similar clearance, volume of distribution, elimination half-life, and urinary recovery...
January 12, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28074057/development-of-new-polymyxin-derivatives-for-multi-drug-resistant-gram-negative-infections
#6
REVIEW
Pamela Brown, Michael J Dawson
Over the last decade, there has been a resurgence of interest in polymyxins owing to the rapid rise in multi-drug resistant Gram-negative bacteria against which polymyxins offer a last-resort treatment. Although having excellent antibacterial activity, the clinical utility of polymyxins is limited by toxicity, especially renal toxicity. There is much interest therefore in developing polymyxin analogues with an improved therapeutic index. This review describes recent work aimed at improving the activity and/or reducing the toxicity of polymyxins...
January 11, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28074004/signaling-by-two-component-system-noncognate-partners-promotes-intrinsic-tolerance-to-polymyxin-b-in-uropathogenic-escherichia-coli
#7
Kirsten R Guckes, Erin J Breland, Ellisa W Zhang, Sarah C Hanks, Navleen K Gill, Holly M S Algood, Jonathan E Schmitz, Charles W Stratton, Maria Hadjifrangiskou
Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators. We describe two distinct TCSs in uropathogenic Escherichia coli (UPEC) that interact to mediate a response to ferric iron...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28071984/particulate-matter-mediated-release-of-long-pentraxin-3-ptx3-and-vascular-endothelial-growth-factor-vegf-in-vitro-limited-importance-of-endotoxin-and-organic-content
#8
J I Herseth, V Volden, A K Bolling
Exposure to particulate matter (PM) is associated with adverse health effects, but it is still relatively unknown which role PM sources and physicochemical properties play in the observed effects. It was postulated that PM in vitro induces release of long pentraxin 3 (PTX3) and vascular endothelial growth factor (VEGF) and that endotoxin and organic compounds present in the PM regulate this release. A contact coculture of THP-1 human leukemia monocytes and A549 human adenocarcinoma alveolar pneumocytes was exposed to PM from Traffic, Wood, Diesel, and Quartz (10-40 µg/cm(2)) for 12-64 h to determine release of PTX3 and VEGF...
January 10, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28071053/functional-characterization-of-the-unique-terminal-thioesterase-domain-from-polymyxin-synthetase
#9
Charles A Galea, Kade D Roberts, Yan Zhu, Philip E Thompson, Jian Li, Tony Velkov
Polymyxins remain one of the few antibiotics available for treating antibiotic resistant bacteria. Here we describe polymyxin B thioesterase which performs the final step in polymyxin B biosynthesis. Isolated thioesterase catalyzed cyclization of an N-acetylcystamine polymyxin B analogue to form polymyxin B. The thioesterase contained a catalytic cysteine unlike most thioesterases which possess a serine. Supporting this, incubation of polymyxin B thioesterase with reducing agents abolished enzymatic activity while mutation of the catalytic cysteine to serine significantly decreased activity...
January 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/28054660/antimicrobial-and-anti-inflammatory-activities-of-three-chensinin-1-peptides-containing-mutation-of-glycine-and-histidine-residues
#10
Weibing Dong, Xiaoman Mao, Yue Guan, Yao Kang, Dejing Shang
The natural peptide chensinin-1 doesnot exhibit its desired biological properties. In this study, the mutant MC1-1 was designed by replacing Gly in the chensinin-1 sequence with Trp. Mutants MC1-2 and MC1-3 were designed based on the MC1-1 sequence to investigate the specific role of His residues. The mutated peptides presented α-helicity in a membrane-mimetic environment and exhibited broad-spectrum antimicrobial activities; in contrast to Trp residues, His residues were dispensable for interacting with the cell membrane...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054415/characterizing-the-effect-of-polymyxin-b-antibiotics-to-lipopolysaccharide-on-escherichia%C3%A2-coli-surface-using-atomic-force-microscopy
#11
Yoo Jin Oh, Birgit Plochberger, Markus Rechberger, Peter Hinterdorfer
Lipopolysaccharide (LPS) on gram-negative bacterial outer membranes is the first target for antimicrobial agents, due to their spatial proximity to outer environments of microorganisms. To develop antibacterial compounds with high specificity for LPS binding, the understanding of the molecular nature and their mode of recognition is of key importance. In this study, atomic force microscopy (AFM) and single molecular force spectroscopy were used to characterize the effects of antibiotic polymyxin B (PMB) to the bacterial membrane at the nanoscale...
January 5, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28052852/high-dose-ampicillin-sulbactam-combinations-combat-polymyxin-resistant-acinetobacter-baumannii-in-a-hollow-fiber-infection-model
#12
Justin R Lenhard, Nicholas M Smith, Zackery P Bulman, Xun Tao, Visanu Thamlikitkul, Beom S Shin, Roger L Nation, Jian Li, Jürgen B Bulitta, Brian T Tsuji
Acinetobacter baumannii are emerging with resistance to polymyxins. In 24h time-killing experiments, high dose ampicillin/sulbactam in combination with meropenem and polymyxin B achieved additivity or synergy against 10(8)CFU/mL of two clinical A. baumannii isolates resistant to all three drugs (max reductions 1.6 and 3.1 logs). In 14-day hollow-fiber infection models, high dose ampicillin/sulbactam (8/4g q8h) in combination with meropenem (2g q8h) and polymyxin B (1.43 mg/kg q12h with loading dose) achieved rapid eradication (96h)...
January 4, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28044098/polymyxins-facilitate-entry-into-mammalian-cells
#13
Kristina M Hamill, Lisa S McCoy, Ezequiel Wexselblatt, Jeffrey D Esko, Yitzhak Tor
Polymyxin B is an antibiotic used against multi-resistant gram negative infections, despite observed nephrotoxicity. Here we report the synthesis of functionalized derivatives of polymyxin B and its per-guanidinylated derivative in order to further explore the structural requirements necessary to facilitate uptake of the antibiotic into mammalian cells. We also investigate the possibility of using these novel scaffolds as molecular transporters. At nanomolar concentrations, both are capable of delivering large cargo (>300 kDa) into living cells...
August 1, 2016: Chemical Science
https://www.readbyqxmd.com/read/28040408/polymyxin-b-in-combination-with-meropenem-against-carbapenemase-producing-klebsiella-pneumoniae-pharmacodynamics-and-morphological-changes
#14
Rajnikant Sharma, Saloni Patel, Cely Abboud, John Diep, Neang S Ly, Jason M Pogue, Keith S Kaye, Jian Li, Gauri G Rao
Combination therapy provides a useful therapeutic approach to overcome resistance until new antibiotics become available. In this study, the pharmacodynamics, including the morphological effects, of polymyxin B (PMB) and meropenem alone and in combination against KPC-producing Klebsiella pneumoniae clinical isolates was examined. Ten clinical isolates were obtained from patients undergoing treatment for mediastinitis. KPCs were identified and MICs were measured using microbroth dilution. Time-kill studies were conducted over 24 h with PMB (0...
December 23, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28024532/-aerogels-of-enzymatically-oxidized-galactomannans-from-leguminous-plants-versatile-delivery-systems-of-antimicrobial-peptides-and-enzymes
#15
Paola Campia, Erika Ponzini, Bianca Rossi, Stefano Farris, Tiziana Silvetti, Luca Merlini, Milena Brasca, Rita Grandori, Yves M Galante
We describe aerogels obtained by laccase/TEMPO-oxidation and lyophilization of galactomannans (GM) from fenugreek, sesbania and guar. Enzymatic oxidation of GM in aqueous solution caused viscosity increase up to fifteen-fold, generating structured, elastic, stable hydrogels, presumably due to establishment of hemiacetalic bonds between newly formed carbonyl groups and free hydroxyl groups. Upon lyophilization, water-insoluble aerogels were obtained, whose mechanical properties and porosity were investigated...
February 20, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28018813/lung-transplantation-in-a-multidrug-resistant-gram-negative-acinetobacter-baumannii-colonized-patient-a-case-report
#16
Katharina Huenges, Alexander Reinecke, Burkhard Bewig, Assad Haneya, Jochen Cremer
Colonization or infection with various pathogens is frequently found in patients listed for lung transplantation. We describe a case of a 50-year-old woman with α-1-antitrypsin deficiency, which was listed for double-lung transplantation, with multidrug-resistant gram-negative Acinetobacter baumannii (MRGN4-Ab) skin colonization. Transplantation was successfully performed. Colistin (Polymyxine E) was administered intravenously and through inhalation in the first month. MRGN4-Ab was still detectable in skin swabs without evidence of infection...
December 2016: Thoracic and Cardiovascular Surgeon Reports
https://www.readbyqxmd.com/read/28013258/epidemiology-of-carbapenem-resistant-klebsiella-pneumoniae-in-a-network-of-long-term-acute-care-hospitals
#17
Jennifer H Han, Ellie J C Goldstein, Jacqueleen Wise, Warren B Bilker, Pam Tolomeo, Ebbing Lautenbach
BACKGROUND: The rapid emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a major public health threat, including in the long-term acute care hospital (LTACH) setting. The objective of this study was to describe the epidemiologic characteristics of CRKP in a network of United States LTACHs. METHODS: An observational study was performed among 64 LTACHs from January 2014 to March 2015. Clinical cultures were included, with the first CRKP isolate recovered from each patient per study quarter evaluated...
December 24, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28012985/effect-of-polymyxin-resistance-pmr-on-biofilm-formation-of-cronobacter-sakazakii
#18
Xuerui Bao, Xiangyin Jia, Lequn Chen, Brian M Peters, Chii-Wann Lin, Dingqiang Chen, Lin Li, Bing Li, Yanyan Li, Zhenbo Xu, Mark E Shirtliff
Cronobacter sakazakii (C.sakazakii) has been identified as a wide-spread conditioned pathogen associated with series of serious illnesses, such as neonatal meningitis, enterocolitis, bacteremia or sepsis. As food safety is concerned, microbial biofilm has been considered to be a potential source of food contamination. The current study aims to investigate the ability of biofilm formation of two C. sakazakii strains (wild type BAA 894 and pmrA mutant). Crystal violet (CV), XTT (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino carbonyl)-2H-(tetrazolium hydroxide)] assays, and scanning electron microscopy (SEM) are performed on different time points during biofilm formation of C...
December 22, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27998750/clinical-translation-of-polymyxin-based-combination-therapy-facts-challenges-and-future-opportunities
#19
REVIEW
Xueli Zhang, Fengmei Guo, Hua Shao, Xiao Zheng
The emergence and spread of multidrug resistant Gram-negative bacteria has led to a resurgence in the clinical use of polymyxin antibiotics. However, the prevalence of polymyxin resistance is on the rise at an alarming rate, motivating the idea of combination therapy to sustain the revival of these "old" antibiotics. Although ample evidence in favor of combination therapy has emerged, it seems impracticable and confusing to find a promising combination from the diverse reports or gain adequate information on the efficacy and safety profile...
December 18, 2016: Journal of Infection
https://www.readbyqxmd.com/read/27995057/rapidly-progressive-interstitial-lung-disease-due-to-anti-mda-5-antibody-positive-clinically-amyopathic-dermatomyositis-complicated-with-cervical-cancer-successful-treatment-with-direct-hemoperfusion-using-polymyxin-b-immobilized-fiber-column-therapy
#20
Hidenori Ichiyasu, Yasumiko Sakamoto, Chieko Yoshida, Kazuhiko Sakamoto, Ryosuke Fujita, Go Nakayama, Hiroko Okabayashi, Sho Saeki, Shinichiro Okamoto, Hirotsugu Kohrogi
The anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is a marker of clinically amyopathic dermatomyositis (CADM) and rapidly progressive interstitial lung disease (ILD) with acute respiratory failure. A 35-year-old woman with cervical cancer showed Gottron's papules, severe hypoxemia, and diffuse ground-glass opacities on chest computed tomography. She was diagnosed with rapidly progressive ILD associated with CADM. Her serum was positive for the anti-MDA-5 antibody. Combination therapy with corticosteroids, immunosuppressants, and direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) improved her respiratory dysfunction...
2017: Respiratory Medicine Case Reports
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