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Polymyxin resistance

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https://www.readbyqxmd.com/read/28096166/the-role-of-renal-drug-exposure-in-polymyxin-b-induced-nephrotoxicity
#1
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/28074057/development-of-new-polymyxin-derivatives-for-multi-drug-resistant-gram-negative-infections
#2
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
#3
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/28071053/functional-characterization-of-the-unique-terminal-thioesterase-domain-from-polymyxin-synthetase
#4
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/28052852/high-dose-ampicillin-sulbactam-combinations-combat-polymyxin-resistant-acinetobacter-baumannii-in-a-hollow-fiber-infection-model
#5
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
#6
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
#7
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/28018813/lung-transplantation-in-a-multidrug-resistant-gram-negative-acinetobacter-baumannii-colonized-patient-a-case-report
#8
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
#9
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
#10
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
#11
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/27992816/prevalence-and-antimicrobial-susceptibility-of-acinetobacter-spp-isolated-from-meat
#12
Ana Carvalheira, Rocio Casquete, Joana Silva, Paula Teixeira
The prevalence and antibiotic resistance of Acinetobacter spp. from fifty samples of meat (chicken, turkey, beef and pork) were evaluated. Acinetobacter spp. was recovered from all samples and the clonal relatedness of 223 isolates identified to belong to the genus Acinetobacter was established by PFGE. A high genetic diversity was observed and 166 isolates from different samples, 141 representing different PFGE profiles, were further identified to the species level by rpoB gene sequencing. Thirteen distinct Acinetobacter species were identified among 156 isolates...
December 6, 2016: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/27958270/crystal-structure-of-escherichia-coli-originated-mcr-1-a-phosphoethanolamine-transferase-for-colistin-resistance
#13
Menglong Hu, Jiubiao Guo, Qipeng Cheng, Zhiqiang Yang, Edward Wai Chi Chan, Sheng Chen, Quan Hao
MCR-1 is a phosphoethanolamine (pEtN) transferase that modifies the pEtN moiety of lipid A, conferring resistance to colistin, which is an antibiotic belonging to the class of polypeptide antibiotics known as polymyxins and is the last-line antibiotic used to treat multidrug resistant bacterial infections. Here we determined the crystal structure of the catalytic domain of MCR-1 (MCR-1-ED), which is originated in Escherichia coli (E. coli). MCR-1-ED was found to comprise several classical β-α-β-α motifs that constitute a "sandwich" conformation...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27940944/colistin-resistance-in-carbapenem-resistant-klebsiella-pneumoniae-laboratory-detection-and-impact-on-mortality
#14
Laura J Rojas, Madiha Salim, Eric Cober, Sandra S Richter, Federico Perez, Robert A Salata, Robert C Kalayjian, Richard R Watkins, Steve Marshall, Susan D Rudin, T Nicholas Domitrovic, Andrea M Hujer, Kristine M Hujer, Yohei Doi, Keith S Kaye, Scott Evans, Vance G Fowler, Robert A Bonomo, David van Duin
BACKGROUND: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. METHODS: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014...
December 10, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27939183/emergence-of-polymyxin-resistance-in-gram-negative-bacteria
#15
EDITORIAL
Abiola Olumuyiwa Olaitan, Jian Li
No abstract text is available yet for this article.
December 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/27935770/from-breast-cancer-to-antimicrobial-combating-extremely-resistant-gram-negative-superbugs-using-novel-combinations-of-polymyxin-b-with-selective-estrogen-receptor-modulators
#16
Maytham H Hussein, Elena K Schneider, Alysha G Elliott, Meiling Han, Felisa Reyes-Ortega, Faye Morris, Mark A T Blastovich, Raad Jasim, Bart Currie, Mark Mayo, Mark Baker, Matthew A Cooper, Jian Li, Tony Velkov
Novel therapeutic approaches are urgently needed to combat nosocomial infections caused by extremely drug-resistant (XDR) "superbugs." This study aimed to investigate the synergistic antibacterial activity of polymyxin B in combination with selective estrogen receptor modulators (SERMs) against problematic Gram-negative pathogens. In vitro synergistic antibacterial activity of polymyxin B and the SERMs tamoxifen, raloxifene, and toremifene was assessed using the microdilution checkerboard and static time-kill assays against a panel of Gram-negative isolates...
December 9, 2016: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/27932081/draft-genome-sequence-of-a-ges-5-producing-serratia-marcescens-isolated-in-southern-brazil
#17
Carolina Silva Nodari, Marina Siebert, Ursula da Silveira Matte, Afonso Luís Barth
Serratia marcescens is a Gram-negative rod intrinsically resistant to polymyxins and usually associated with wound, respiratory and urinary tract infections. The whole genome of the first GES-5-producing S. marcescens isolated from a Brazilian patient was sequenced using Ion Torrent PGM System. Besides blaGES-5, we were able to identify genes encoding for other β-lactamases, for aminoglycoside modifying enzymes and for an efflux pump to tetracyclines.
November 23, 2016: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/27924470/emerging-issues-and-treatment-strategies-in-carbapenem-resistant-enterobacteriaceae-cre
#18
REVIEW
Dana R Bowers, Vanthida Huang
Carbapenems are the broadest spectrum antimicrobials utilized in the treatment of serious infections since the 1980s. Soon after their introduction, the discovery of carbapenem-resistant Enterobacteriaceae (CRE) was reported in the 1990s. Invasive CRE infections are associated with high mortality and limited treatment options making care for patients with these infections challenging for clinicians. Current practice has reverted back to the use of "older" antimicrobials, such as the polymyxins, tigecycline, and fosfomycin, to combat invasive CRE infections...
December 2016: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/27923523/polysorbate-80-and-polymyxin-b-inhibit-stenotrophomonas-maltophilia-biofilm
#19
Adam M Malinowski, Bryan M McClarty, Carolyn Robinson, William Spear, Maria Sanchez, Timothy C Sparkes, Joanna S Brooke
Stenotrophomonas maltophilia is an opportunistic multiple-drug-resistant human pathogen that forms biofilms on implanted medical devices. We examined the potential inhibitory activity of polysorbate 80 and polymyxin B against S. maltophilia. A combination of subMIC polymyxin B and polysorbate 80 was the most effective inhibitor of growth and biofilm formation.
February 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/27905924/current-knowledge-and-perspectives-of-paenibacillus-a-review
#20
REVIEW
Elliot Nicholas Grady, Jacqueline MacDonald, Linda Liu, Alex Richman, Ze-Chun Yuan
Isolated from a wide range of sources, the genus Paenibacillus comprises bacterial species relevant to humans, animals, plants, and the environment. Many Paenibacillus species can promote crop growth directly via biological nitrogen fixation, phosphate solubilization, production of the phytohormone indole-3-acetic acid (IAA), and release of siderophores that enable iron acquisition. They can also offer protection against insect herbivores and phytopathogens, including bacteria, fungi, nematodes, and viruses...
December 1, 2016: Microbial Cell Factories
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