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Polymyxin-b

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https://www.readbyqxmd.com/read/28416543/potential-toxicity-of-polymyxins-in-human-lung-epithelial-cells
#1
Maizbha U Ahmed, Tony Velkov, Yu-Wei Lin, Bo Yun, Cameron J Nowell, Fanfan Zhou, Qi Tony Zhou, Kim Chan, Mohammad A K Azad, Jian Li
Inhaled polymyxins are of considerable utility to achieve optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical and often high doses are used which may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial cells (A549). Viability of A549 cells was examined after treatment with polymyxins using flow cytometry. Activation of caspase-3, -8, -9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential and mitochondrial oxidative stress induced by polymyxin B was evaluated...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28406770/frequency-and-antibiogram-of-isolates-from-surgical-units-of-a-tertiary-care-hospital-in-quetta
#2
Maria Mushtaq Gill, Muhammad Junaid Khan, Muhammad Asif Nawaz, Sarfraz Khan Janjua
OBJECTIVE: To determine the frequency and antibiogram of the isolates from infected patients in surgical units of a tertiary care hospital. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Department of Microbiology, Combined Military Hospital, Quetta, from March to October 2015. METHODOLOGY: Clinical samples from the surgical units received in Department of Microbiology for culture and sensitivity were analyzed by Gram stain, culture and biochemical tests for identification of the isolates; and the antibiotic susceptibility was determined by modified Kirby Bauer disc diffusion method...
March 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28396353/the-histidine-residue-of-qsec-is-required-for-canonical-signaling-between-qseb-and-pmrb-in-uropathogenic-escherichia-coli
#3
Erin J Breland, Ellisa W Zhang, Tomas Bermudez, Charles R Martinez, Maria Hadjifrangiskou
Two-component systems are prototypically comprised of a histidine kinase (sensor) and a response regulator (responder). The sensor kinases auto-phosphorylate at a conserved histidine residue, acting as a phospho-donor for subsequent phosphotransfer to and activation of a cognate response regulator. In rare cases, the histidine residue is also essential for response regulator de-phosphorylation via a reverse-phosphotransfer reaction. In this work, we present an example of a kinase that relies on reverse-phosphotransfer to catalyze the de-phosphorylation of its cognate partner...
April 10, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28394975/-risk-factors-for-acute-kidney-injury-in-patients-treated-with-polymyxin-b-experience-from-139-cases-at-a-tertiary-university-hospital-in-colombia
#4
Johanna Osorio, Jackeline Barreto, Claudia F Samboni, Lina A Cándelo, Luis C Álvarez, Susana Benavidez, Roso P Téllez, Dagoberto Santofimio, Jorge A Ramos, Carlos A Gómez
BACKGROUND: The rise of infections caused by multidrug-resistant Gram negative bacilli (MDR-GNB), added to paucity of newer therapy, have led to increase polymyxin B use, despite adverse renal toxicity profile. AIM: To determine the incidence and risk factors associated to acute kidney injury (AKI) and polymyxin B use, in patients with infections caused by MDR-GNB. METHODS: A retrospective cohort, with a nested case-control study of adults who received polymyxin B for more than 48 hours at a tertiary university hospital in Colombia (2011-2015) was performed...
February 2017: Revista Chilena de Infectología: órgano Oficial de la Sociedad Chilena de Infectología
https://www.readbyqxmd.com/read/28390976/rough-brucella-strain-rm57-is-attenuated-and-confers-protection-against-brucella-melitensis
#5
Yu Feng, Xiaowei Peng, Hui Jiang, Yong Peng, Liangquan Zhu, Jiabo Ding
Brucella melitensis (B. melitensis) is a facultative intracellular pathogen, which is the main epidemic strain in China. To overcome disadvantages of traditional live attenuated vaccines, in this study a rough mutant RM57 was induced from a B. melitensis isolate M1981. In order to uncover the reason of changes in the LPS of RM57, the nucleotide sequences and transcription levels of all known genes related to LPS synthesis were detected. As LPS plays an important role in outer membrane integrity, the sensitivities of RM57 to SDS and polymyxin B were examined...
April 5, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28384882/polymyxin-b-induced-diffuse-cutaneous-hyperpigmentation
#6
Sandeep Lahiry, Shouvik Choudhury, Ayan Mukherjee, Prajesh Kiran Bhunya, Moumita Bala
Polymyxin B is a polypeptide-antibiotic, primarily used for resistant Gram-negative infections, first obtained from bacterium Bacillus polymyxa in the late 1940s. Antibiotic spectrum are restricted to mainly gram negative bacterias like Enterobacter, E. coli, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella; and particularly organisms like Pseudomonas aeruginosa and Acinetobacter baumannii, which are extremely potent to acquire antibiotic resistance. Side effects include neurotoxicity and acute renal tubular necrosis...
February 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28382472/omp31-plays-an-important-role-on-outer-membrane-properties-and-intracellular-survival-of-brucella-melitensis-in-murine-macrophages-and-hela-cells
#7
L Verdiguel-Fernández, R Oropeza-Navarro, Francisco J Basurto-Alcántara, A Castañeda-Ramírez, Antonio Verdugo-Rodríguez
Brucellosis is an infectious disease that affects practically all species of mammals, including human, and is a major zoonosis worldwide. Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in phagocytic and nonphagocytic cells such as trophoblast and epithelial cells. Among the six recognized species of the genus Brucella, Brucella melitensis is the main etiological agent involved in goat brucellosis and is also the most pathogenic for human. It causes significant losses in livestock production as a result of abortions, metritis, infertility, and birth of weak animals...
April 5, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28367020/comparison-of-four-phenotypic-methods-for-detection-of-metallo-%C3%AE-lactamase-producing-gram-negative-bacteria-in-rural-teaching-hospital
#8
Chinjal A Panchal, Sweta Sunil Oza, Sanjay J Mehta
CONTEXT: Metallo-β-lactamase (MBL)-producing bacteria lead to resistance to carbapenem an antibiotic that used as the last resort for treatment of multidrug-resistant bacteria, extended spectrum beta-lactamases, and AmpC β-lactamase-producing Gram-negative bacteria (GNB). The emergence of MBL-producing GNB is challenge to microbiology laboratories because there are no standardized guidelines available to detect them. The aim of this study was to compare four phenotypic methods to detect MBL production in GNB and to determine antibiotic sensitivity of MBL-producing isolates...
April 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28358803/efficacy-of-polymyxin-b-immobilized-fiber-hemoperfusion-for-patients-with-septic-shock-caused-by-gram-negative-bacillus-infection
#9
Nobuyuki Saito, Kazuhiro Sugiyama, Testu Ohnuma, Takashi Kanemura, Michitaka Nasu, Yuya Yoshidomi, Yuta Tsujimoto, Hiroshi Adachi, Hiroyuki Koami, Aito Tochiki, Kota Hori, Yukiko Wagatsuma, Hisashi Matsumoto
Septic shock-associated mortality in intensive care units (ICUs) remains high, with reported rates ranging 30-50%. In particular, Gram-negative bacilli (GNB), which induce significant inflammation and consequent multiple organ failure, are the etiological bacterial agent in 40% of severe sepsis cases. Hemoperfusion using polymyxin B-immobilized fiber (PMX), which adsorbs endotoxin, is expected to reduce the inflammatory sepsis cascade due to GNB. However, the clinical efficacy of this treatment has not yet been demonstrated...
2017: PloS One
https://www.readbyqxmd.com/read/28353411/polymyxin-b-and-vancomycin-associated-acute-kidney-injury-in-critically-ill-patients
#10
Douglas de Sousa Soares, André da Fonte Reis, Geraldo Bezerra da Silva Junior, Tacyano Tavares Leite, Sérgio Luiz Arruda Parente Filho, Carina Vieira de Oliveira Rocha, Elizabeth De Francesco Daher
BACKGROUND: This study aims to investigate renal toxicities of Polymyxin B and Vancomycin among critically ill patients and risk factors for acute kidney injury (AKI). METHODS: This is a cross-sectional study conducted with patients admitted to an intensive care unit (ICU) of a tertiary hospital in Brazil. Patients were divided into two groups: those who used association of Polymyxin B + Vancomycin (Group I) and those who used only Polymyxin B (Group II). Risk factors for AKI were also analyzed...
March 29, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28351920/spxa1-and-spxa2-act-coordinately-to-fine-tune-stress-responses-and-virulence-in-streptococcus-pyogenes
#11
Gary C Port, Zachary T Cusumano, Paul R Tumminello, Michael G Caparon
SpxA is a unique transcriptional regulator highly conserved among members of the phylum Firmicutes that binds RNA polymerase and can act as an antiactivator. Why some Firmicutes members have two highly similar SpxA paralogs is not understood. Here, we show that the SpxA paralogs of the pathogen Streptococcus pyogenes, SpxA1 and SpxA2, act coordinately to regulate virulence by fine-tuning toxin expression and stress resistance. Construction and analysis of mutants revealed that SpxA1(-) mutants were defective for growth under aerobic conditions, while SpxA2(-) mutants had severely attenuated responses to multiple stresses, including thermal and oxidative stresses...
March 28, 2017: MBio
https://www.readbyqxmd.com/read/28343078/development-and-validation-of-liquid-chromatography-tandem-mass-spectrometry-method-quantitative-determination-of-polymyxin-b1-polymyxin-b2-polymyxin-b3-and-isoleucine-polymyxin-b1-in-human-plasma-and-its-application-in-clinical-studies
#12
Kim H Hee, Yee K J Leaw, Jun L Ong, Lawrence S Lee
Polymyxin B (PB) is an antibiotic consisting of a cyclic heptapeptide and a tripeptide side chain used in treatment of infections caused by Gram-negative bacteria. Commercial formulations of PB contain multiple structurally related components with major constituents of PB1, PB2, PB3 and ile-PB1. To understand the pharmacokinetics of these major components, we have developed and validated a LC-MS/MS method to quantify PB1, PB2, PB3 and ile-PB1 in human plasma. PB was extracted from plasma by protein precipitation using trichloroacetic acid followed by chromatographic separation on Zorbax Bonus-RP column (100mm×2...
March 14, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28342805/phosphoethanolamine-addition-to-the-heptose-i-of-the-lipopolysaccharide-modifies-the-inner-core-structure-and-has-an-impact-on-the-binding-of-polymyxin-b-to-the-escherichia-coli-outer-membrane
#13
Javier Salazar, Mackarenna Alarcón, Jaime Huerta, Belén Navarro, Daniel Aguayo
Phosphoethanolamine (pEtN) decoration of E. coli Lipopolysaccharide (LPS) provides resistance to the antimicrobial Polymyxin B (PolB). While EptA and EptB enzymes catalyze the addition of pEtN to the Lipid A and Kdo (pEtN-Kdo-Lipid A), EptC catalyzes the pEtN addition to the Heptose I (pEtN-HeptI). In this study, we investigated the contribution of pEtN-HeptI to PolB resistance using eptA/eptB and eptC deficient E. coli K12 and its wild-type parent strains. These mutations were shown to decrease the antimicrobial activity of PolB on cells grown under pEtN-addition inducing conditions...
April 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28334005/multi-scale-model-of-drug-induced-adaptive-resistance-of-gram-negative-bacteria-to-polymyxin-b
#14
Wojciech Krzyzanski, Gauri G Rao
The purpose of this report is to apply multi-scale modeling using the theory of physiologically structured populations (PSP) to develop a mathematical model for antimicrobial resistance based on a heterogeneous distribution of receptors and affinities among bacterial cells. The theory has been tested on data obtained from an in vitro static time-kill infection model analyzing the pharmacodynamics of polymyxin B against Gram-negative bacteria. The drug binding parameter KD (dissociation equilibrium constant) is assumed to vary between the bacterial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28333347/polymyxin-resistant-carbapenem-resistant-acinetobacter-baumannii-is-eradicated-by-a-triple-combination-of-agents-that-lack-individual-activity
#15
Justin R Lenhard, Visanu Thamlikitkul, Fernanda P Silveira, Samira M Garonzik, Xun Tao, Alan Forrest, Beom Soo Shin, Keith S Kaye, Jürgen B Bulitta, Roger L Nation, Jian Li, Brian T Tsuji
Objectives: The emergence of polymyxin resistance threatens to leave clinicians with few options for combatting drug-resistant Acinetobacter baumannii . The objectives of the current investigation were to define the in vitro emergence of polymyxin resistance and identify a combination regimen capable of eradicating A. baumannii with no apparent drug susceptibilities. Methods: Two clonally related, paired, A. baumannii isolates collected from a critically ill patient who developed colistin resistance while receiving colistin methanesulfonate in a clinical population pharmacokinetic study were evaluated: an A...
February 28, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332430/preparation-of-pva-amino-multi-walled-carbon-nanotubes-nanocomposite-microspheres-for-endotoxin-adsorption
#16
Wenhui Zong, Jian Chen, Wenyan Han, Guanghui Cheng, Jie Chen, Yue Wang, Weichao Wang, Lailiang Ou, Yaoting Yu, Jie Shen
A novel polyvinyl alcohol-amino multi-walled carbon nanotube (PVA-AMWCNT) nanocomposite microsphere was prepared successfully for the first time and used for endotoxin removal. The resulting AMWCNT modified PVA microsphere was characterized by SEM, Raman spectrum and fluorescence image, which indicated AMWCNT was dispersed into the macropores of PVA microsphere uniformly. The PVA-AMWCNT microspheres showed better adsorption capability and faster adsorption equilibrium for endotoxin in aqueous solution when compared to the PVA microsphere with polymyxin B (PMB) as ligand...
March 23, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28316480/inducible-spy-transcription-acts-as-a-sensor-for-envelope-stress-of-salmonella-typhimurium
#17
Seon Mi Jeong, Hwa Jeong Lee, Yoon Mee Park, Jin Seok Kim, Sang Dae Lee, Iel Soo Bang
Salmonella enterica infects a broad range of host animals, and zoonostic infection threatens both public health and the livestock and meat processing industries. Many antimicrobials have been developed to target Salmonella envelope that performs essential bacterial functions; however, there are very few analytical methods that can be used to validate the efficacy of these antimicrobials. In this study, to develop a potential biosensor for Salmonella envelope stress, we examined the transcription of the S. enterica serovar typhimurium spy gene, the ortholog of which in Escherichia coli encodes Spy (spheroplast protein y)...
2017: Korean Journal for Food Science of Animal Resources
https://www.readbyqxmd.com/read/28306723/the-redefinition-of-helicobacter-pylori-lipopolysaccharide-o-antigen-and-core-oligosaccharide-domains
#18
Hong Li, Tiandi Yang, Tingting Liao, Aleksandra W Debowski, Hans-Olof Nilsson, Alma Fulurija, Stuart M Haslam, Barbara Mulloy, Anne Dell, Keith A Stubbs, Barry J Marshall, Mohammed Benghezal
Helicobacter pylori lipopolysaccharide promotes chronic gastric colonisation through O-antigen host mimicry and resistance to mucosal antimicrobial peptides mediated primarily by modifications of the lipid A. The structural organisation of the core and O-antigen domains of H. pylori lipopolysaccharide remains unclear, as the O-antigen attachment site has still to be identified experimentally. Here, structural investigations of lipopolysaccharides purified from two wild-type strains and the O-antigen ligase mutant revealed that the H...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28302074/clonality-outer-membrane-proteins-profile-and-efflux-pump-in-kpc-producing-enterobacter-sp-in-brazil
#19
Juliana Ferraz Rosa, Camila Rizek, Ana Paula Marchi, Thais Guimaraes, Lourdes Miranda, Claudia Carrilho, Anna S Levin, Silvia F Costa
BACKGROUND: Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year. METHODS: Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates...
March 17, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28300674/structure-activity-studies-on-polymyxin-derivatives-carrying-three-positive-charges-only-reveal-a-new-class-of-compounds-with-strong-antibacterial-activity
#20
Martti Vaara, Timo Vaara, Jonathan M Tyrrell
Recent years have brought in an increased interest to develop improved polymyxins. The currently used polymyxins, i.e. polymyxin B and colistin (polymyxin E) are pentacationic lipopeptides that possess a cyclic heptapeptide part with three positive charges, a linear "panhandle" part with two positive charges, and a fatty acyl tail. Unfortunately, their clinical use is shadowed by their notable nephrotoxicity. We have previously developed a polymyxin derivative NAB739 which lacks the positive charges in the linear part...
March 11, 2017: Peptides
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