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Polymyxins

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https://www.readbyqxmd.com/read/29150371/emergence-of-polymyxin-b-resistance-in-a-polymyxin-b-susceptible-kpc-producing-klebsiella-pneumoniae-causing-bloodstream-infection-in-a-neutropenic-patient-during-polymyxin-b-therapy
#1
Alexandre P Zavascki, Raquel Girardello, Cibele M Magagnin, Laura C Antochevis, Rafael A Maciel, Jussara K Palmeiro, Ana C Gales
The emergence of resistance to polymyxins in KPC-producing Klebsiella pneumoniae isolates has been a major clinical problem. This study evaluated the molecular mechanisms associated with polymyxin B (PMB) resistance that emerged in a previously PMB-susceptible KPC-2-producing K. pneumoniae during PMB therapy for a bloodstream infection in a neutropenic patient. The first isolate (PMB-susceptible) was obtained while the patient was receiving meropenem and other isolates were recovered from 2 sets of blood cultures in different dates while the patient was receiving PMB therapy (4 of 6 blood cultures bottles yielded isolates with full PMB resistance)...
October 19, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29149329/polymyxin-derivatives-nab739-and-nab815-are-more-effective-than-polymyxin-b-in-murine-escherichia-coli-pyelonephritis
#2
Martti Vaara, Timo Vaara, Carina Vingsbo Lundberg
Objectives: Extremely multiresistant strains of Enterobacteriaceae, such as those of Escherichia coli and Klebsiella pneumoniae, are emerging and spreading at a worrisome speed. Polymyxins (polymyxin B, colistin) are used as last-line therapy against such strains, in spite of their notable nephrotoxicity that may even require discontinuation of the therapy. We have previously developed polymyxin derivatives NAB739 and NAB815 that are better tolerated in cynomolgus monkeys than polymyxin B and are, in contrast to polymyxin B, excreted in the cynomolgus urine to a very significant degree...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29149294/pharmacokinetics-pharmacodynamics-of-systemically-administered-polymyxin-b-against-klebsiella-pneumoniae-in-mouse-thigh-and-lung-infection-models
#3
Cornelia B Landersdorfer, Jiping Wang, Veronika Wirth, Ke Chen, Keith S Kaye, Brian T Tsuji, Jian Li, Roger L Nation
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later...
November 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29148380/high-rate-of-mcr-1-producing-escherichia-coli-and-klebsiella-pneumoniae-among-pigs-portugal
#4
Nicolas Kieffer, Marta Aires-de-Sousa, Patrice Nordmann, Laurent Poirel
The mcr-1 (mobile colistin resistance 1) gene, which encodes phosphoethanolamine transferase, has been recently identified as a source of acquired resistance to polymyxins in Escherichia coli. Using the SuperPolymyxin selective medium, we prospectively screened 100 pigs at 2 farms in Portugal for polymyxin-resistant Enterobacteriaceae and recovered 98 plasmid-mediated MCR-1-producing isolates. Most isolates corresponded to nonclonally related E. coli belonging to many sequence types; we also found 2 Klebsiella pneumoniae sequence types...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29147502/chemical-space-guided-discovery-of-antimicrobial-bridged-bicyclic-peptides-against-pseudomonas-aeruginosa-and-its-biofilms
#5
Ivan Di Bonaventura, Xian Jin, Ricardo Visini, Daniel Probst, Sacha Javor, Bee-Ha Gan, Gaëlle Michaud, Antonino Natalello, Silvia Maria Doglia, Thilo Köhler, Christian van Delden, Achim Stocker, Tamis Darbre, Jean-Louis Reymond
Herein we report the discovery of antimicrobial bridged bicyclic peptides (AMBPs) active against Pseudomonas aeruginosa, a highly problematic Gram negative bacterium in the hospital environment. Two of these AMBPs show strong biofilm inhibition and dispersal activity and enhance the activity of polymyxin, currently a last resort antibiotic against which resistance is emerging. To discover our AMBPs we used the concept of chemical space, which is well known in the area of small molecule drug discovery, to define a small number of test compounds for synthesis and experimental evaluation...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29146285/rapid-polymyxin-np-test-for-the-detection-of-polymyxin-resistance-mediated-by-the-mcr-1-mcr-2-genes
#6
Laurent Poirel, Yu Larpin, Jan Dobias, Roger Stephan, Jean-Winoc Decousser, Jean-Yves Madec, Patrice Nordmann
The Rapid Polymyxin NP test has been recently developed to rapidly detect polymyxin resistance in Enterobacteriaceae. Here we evaluated this test for detecting MCR-1/MCR-2-producing Enterobacteriaceae using a collection of 70 non-redundant strains either recovered from the environment, animals, or humans. Sensitivity and specificity were found to be 100%.
September 22, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29138303/cxc-chemokines-exhibit-bactericidal-activity-against-multidrug-resistant-gram-negative-pathogens
#7
Matthew A Crawford, Debra J Fisher, Lisa M Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli, Tommaso Giani, Gian Maria Rossolini, Yohei Doi, David R Goodlett, Marc W Allard, Shashi K Sharma, Erum Khan, Robert K Ernst, Molly A Hughes
The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29137129/design-and-evaluation-of-novel-polymyxin-fluorescent-probes
#8
Bo Yun, Kade D Roberts, Philip E Thompson, Roger L Nation, Tony Velkov, Jian Li
Polymyxins (polymyxin B and colistin) are cyclic lipopeptide antibiotics that serve as a last-line defence against Gram-negative "superbugs". In the present study, two novel fluorescent polymyxin probes were designed through regio-selective modifications of the polymyxin B core structure at the N-terminus and the hydrophobic motif at positions 6 and 7. The resulting probes, FADDI-285 and FADDI-286 demonstrated comparable antibacterial activity (MICs 2-8 mg/L) to polymyxin B and colistin (MICs 0.5-8 mg/L) against a panel of gram-negative clinical isolates of Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa...
November 11, 2017: Sensors
https://www.readbyqxmd.com/read/29136469/novel-linear-lipopeptide-paenipeptins-with-potential-for-eradicating-biofilms-and-sensitizing-gram-negative-bacteria-to-rifampicin-and-clarithromycin
#9
Sun Hee Moon, Xuan Zhang, Guangrong Zheng, Daniel G Meeker, Mark S Smeltzer, En Huang
We report the structure-activity relationship (SAR) analyses of 17 linear lipopeptide paenipeptin analogues. Analogues 7, 12 and 17 were more potent than the lead compound. Analogue 17 was active against carbapenem-resistant and polymyxin-resistant pathogens. This compound at 40 μg/mL resulted in 3 log and 2.6 log reductions of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in catheter-associated biofilms in vitro. Analogue 17 showed little hemolysis at 32 µg/ml and lysed 11% of red blood cells at 64 µg/ml...
November 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29123880/efficacy-of-direct-hemoperfusion-with-a-polymyxin-b-immobilized-fiber-column-in-miliary-tuberculosis
#10
Yasumasa Kawano, Ryotaro Nagashima, Shinichi Morimoto, Yoshito Izutani, Reiko Yamasaki, Takeshi Nishida, Mitsutoshi Iwaasa, Hiroyasu Ishikura
Case: A 75-year-old woman presented with a 10-day history of intermittent fever, general fatigue, and progressive dyspnea. Although she had a low PaO2/FIO2 ratio, the cause of acute respiratory distress syndrome was not clear until day 9 in hospital. Outcome: We treated the patient with direct hemoperfusion with a polymyxin B-immobilized fiber column incidentally; the PaO2/FIO2 ratio improved following this therapy. Acid-fast bacilli, which were not seen in the sputum on admission, were detected in cultures from sputum, urine, bone marrow, liver biopsy, and blood samples, with a real-time polymerase chain reaction assay confirming tuberculosis...
July 2017: Acute Medicine & Surgery
https://www.readbyqxmd.com/read/29120716/cost-comparison-of-commonly-used%C3%A2-postoperative-topical-ophthalmic%C3%A2-antibiotics
#11
Eric L Crowell, Vivek A Koduri, R Scott Groat, David A Lee
PURPOSE: To provide information on the actual fill level and cost of currently available antibiotic drops used perioperatively. DESIGN: Prospective laboratory investigation. SETTING: Robert Cizik Eye Clinic, Houston, Texas USA. METHODS: The following 9 medications were tested: moxifloxacin, gatifloxacin (branded and generic), besifloxacin, levofloxacin, ciprofloxacin, ofloxacin, trimethoprim/polymyxin B, tobramycin, and gentamicin...
October 2017: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/29117525/membrane-cholesterol-reduces-polymyxin-b-nephrotoxicity-in-renal-membrane-analogs
#12
Adree Khondker, Richard J Alsop, Alexander Dhaliwal, Sokunthearath Saem, Jose M Moran-Mirabal, Maikel C Rheinstädter
Polymyxin B (PmB) is a "last-line" antibiotic scarcely used due to its nephrotoxicity. However, the molecular basis for antibiotic nephrotoxicity is not clearly understood. We prepared kidney membrane analogs of detergent-susceptible membranes, depleted of cholesterol, and cholesterol enriched, resistant membranes. In both analogs, PmB led to membrane damage. By combining x-ray diffraction, molecular dynamics simulations, and electrochemistry, we present evidence for two populations of PmB molecules: peptides that lie flat on the membranes, and an inserted state...
November 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29117270/screening-for-the-presence-of-mcr-1-mcr-2-genes-in-shiga-toxin-producing-escherichia-coli-recovered-from-a-major-produce-production-region-in-california
#13
Daniela Mavrici, Jaszemyn C Yambao, Bertram G Lee, Beatriz Quiñones, Xiaohua He
The rapid spreading of polymyxin E (colistin) resistance among bacterial strains through the horizontally transmissible mcr-1 and mcr-2 plasmids has become a serious concern. The emergence of these genes in Shiga toxin-producing Escherichia coli (STEC), a group of human pathogenic bacteria was even more worrisome, urging us to investigate the prevalence of mcr genes among STEC isolates. A total of 1000 STEC isolates, recovered from livestock, wildlife, produce and other environmental sources in a major production region for leafy vegetables in California during 2006-2014, were screened by PCR for the presence of plasmid-borne mcr-1 and mcr-2...
2017: PloS One
https://www.readbyqxmd.com/read/29114023/mcr-1-inhibition-with-peptide-conjugated-phosphorodiamidate-morpholino-oligomers-restores-sensitivity-to-polymyxin-in-escherichia-coli
#14
Seth M Daly, Carolyn R Sturge, Christina F Felder-Scott, Bruce L Geller, David E Greenberg
In late 2015, the first example of a transferrable polymyxin resistance mechanism in Gram-negative pathogens, MCR-1, was reported. Since that report, MCR-1 has been described to occur in many Gram-negative pathogens, and the mechanism of MCR-1-mediated resistance was rapidly determined: an ethanolamine is attached to lipid A phosphate groups, rendering the membrane more electropositive and repelling positively charged polymyxins. Acquisition of MCR-1 is clinically significant because polymyxins are frequently last-line antibiotics used to treat extensively resistant organisms, so acquisition of this mechanism might lead to pan-resistant strains...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29107079/clonal-spread-of-carbapenem-resistant-acinetobacter-baumannii-in-neonatal-intensive-care-unit
#15
Wirlaine Glauce Maciel, Kesia Esther da Silva, Julio Croda, Rodrigo Cayô, Ana Carolina Ramos, Romário Oliveira de Sales, Gleyce Hellen de Almeida de Souza, José Victor Bortolotto Bampi, Leticia Cristina Limiere, Junior César Casagrande, Ana Cristina Gales, Simone Simionatto
Acinetobacter baumannii has been frequently associated with colonization and/or infection in neonatal intensive care units (NICU). In this study, we describe a clonal spread of carbapenem-resistant A. baumannii (CRAB) isolates in a NICU. A total of 21 CRAB isolates were collected from premature newborns. Only polymyxin B was active against such isolates. Nineteen CRAB isolates were clonally related (cluster C that belonged to worldwide-disseminated ST1). All newborns had peripheral access and previously received β-lactams therapy...
October 26, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/29105371/mast-cells-partially-contribute-to-mucosal-adjuvanticity-of-surfactin-in-mice
#16
Naoto Yoshino, Ryosuke Takeshita, Hanae Kawamura, Yutaka Sasaki, Masahiro Kagabu, Toru Sugiyama, Yasushi Muraki, Shigehiro Sato
INTRODUCTION: Surfactin (SF) is a cyclic lipopeptide that has potent mucosal adjuvant properties. However, immunological mechanisms of SF adjuvant action have not yet been elucidated. As some cyclic lipopeptides, such as polymyxin, can stimulate histamine release from mast cells, we hypothesized that mast cell activation is critical for SF adjuvanticity. METHODS/RESULTS: We observed that following intranasal immunization with ovalbumin (OVA) plus SF, the titers of the OVA-specific antibody (Ab) in the mucosal secretions and plasma of mast cell-deficient mice were significantly lower than those in congenic normal mice, although OVA-specific Ab did not entirely disappear from mast cell-deficient mice...
November 3, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29101229/-almg-responsible-for-polymyxin-resistance-in-pandemic-v-cholerae-is-a-glycyl-transferase-distantly-related-to-lipid-a-late-acyltransferases
#17
Jeremy C Henderson, Carmen M Herrera, M Stephen Trent
Cationic antimicrobial peptides (CAMPs), such as polymyxins are used as a last-line defense in treatment of many bacterial infections. However, some bacteria have developed resistance mechanisms to survive these compounds. Current pandemic O1 Vibrio cholerae biotype El Tor is resistant to polymyxins, whereas previous pandemic strain of the classical biotype is polymyxin sensitive. The almEFG operon found in El Tor V. cholerae confers >100-fold resistance to antimicrobial peptides through aminoacylation of lipopolysaccharide (LPS), expected to decrease the negatively charged surface of the V...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29094001/in-vitro-synergy-of-antibiotic-combinations-against-planktonic-and-biofilm-pseudomonas-aeruginosa
#18
Hossein Ghorbani, Mohammad Yousef Memar, Fatemeh Yeganeh Sefidan, Mina Yekani, Reza Ghotaslou
Aim: The combination of different antimicrobial agents and subsequent synergetic effects may be beneficial in treatment of P. aeruginosa infections. The aim of the present study was to determine antibiotic susceptibility patterns of clinical isolates of P. aeruginosa and the effect of different antibiotic combinations against the multidrug-resistant (MDR), biofilm-producing bacterium P. aeruginosa. Methods: Thirty-six P. aeruginosa clinical isolates were evaluated. The disk diffusion method was performed to determine antibiotic susceptibility patterns according to the Clinical and Laboratory Standards Institute (CLSI) guidelines...
2017: GMS Hygiene and Infection Control
https://www.readbyqxmd.com/read/29093381/the-serum-ferritin-level-is-associated-with-the-treatment-responsivity-for-rapidly-progressive-interstitial-lung-disease-with-amyopathic-dermatomyositis-irrespective-of-the-anti-mda5-antibody-level-a-case-report
#19
Takeshi Osawa, Kozo Morimoto, Yuka Sasaki, Shuichi Matsuda, Kazunari Yamana, Ryozo Yano, Takashi Uchiyama, Hajime Goto
We herein report he case of a 61-year-old woman with rapidly progressive interstitial lung disease caused by clinically amyopathic dermatomyositis. Both the serum ferritin and anti-MDA5 antibody levels were elevated at the time of admission. Despite intensive treatment with corticosteroids, immunosuppressants, immunoglobulins and polymyxin B direct hemoperfusion, the patient died 75 days after symptom onset. Over the course of treatment, the anti-MDA5 antibody level continually decreased, while the serum ferritin level increased, suggesting that sequential measurements of the serum ferritin level might be useful for evaluating the treatment responsivity, irrespective of the anti-MDA5 antibody level...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29092042/expanding-the-potential-of-nai-107-for-treating-serious-eskape-pathogens-synergistic-combinations-against-gram-negatives-and-bactericidal-activity-against-non-dividing-cells
#20
Cristina Brunati, Thomas T Thomsen, Eleonora Gaspari, Sonia Maffioli, Margherita Sosio, Daniela Jabes, Anders Løbner-Olesen, Stefano Donadio
Objectives: To characterize NAI-107 and related lantibiotics for their in vitro activity against Gram-negative pathogens, alone or in combination with polymyxin, and against non-dividing cells or biofilms of Staphylococcus aureus. NAI-107 was also evaluated for its propensity to select or induce self-resistance in Gram-positive bacteria. Methods: We used MIC determinations and chequerboard experiments to establish the antibacterial activity of the examined compounds against target microorganisms...
October 30, 2017: Journal of Antimicrobial Chemotherapy
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