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Polymyxin resistant

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https://www.readbyqxmd.com/read/28533232/potentiation-of-antibiotic-activity-by-a-novel-cationic-peptide-potency-and-spectrum-of-activity-of-spr741
#1
David Corbett, Andrew Wise, Tara Langley, Kirsty Skinner, Emily Trimby, Stephen Birchall, Alain Dorali, Stephanie Sandiford, Jennifer Williams, Peter Warn, Martti Vaara, Troy Lister
Novel approaches to the treatment of multi-drug resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacy of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii Of 35 antibiotics tested, the MICs of eight were reduced 32- to 8,000-fold against E...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28505268/pharmacodynamics-of-dose-escalated-front-loading-polymyxin-b-regimens-against-polymyxin-resistant-mcr-1-harbouring-escherichia-coli
#2
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/28497462/skin-hyperpigmentation-following-intravenous-polymyxin-b-treatment-associated-with-melanocyte-activation-and-inflammatory-process
#3
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/28487432/deciphering-mcr-2-colistin-resistance
#4
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
#5
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/28463513/characterization-of-the-polymyxin-d-synthetase-biosynthetic-cluster-and-product-profile-of-paenibacillus-polymyxa-atcc-10401
#6
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/28458051/emergence-and-nosocomial-spread-of-carbapenem-resistant-oxa-232-producing-klebsiella-pneumoniae-in-brunei-darussalam
#7
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
#8
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...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28457352/carbapenem-resistant-enterobacteriaceae
#9
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
#10
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/28454673/synthesis-of-octapeptin-c4-and-biological-profiling-against-ndm-1-and-polymyxin-resistant-bacteria
#11
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.
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28443813/vacuolar-h-atpase-subunit-vma1p-functions-as-the-molecular-ligand-in-the-vacuole-targeting-fungicidal-activity-of-polymyxin-b
#12
Maki Iida, Keiichi Yamada, Yoshiya Nango, Yoshihiro Yamaguchi, Akira Ogita, Ken-Ichi Fujita, Toshio Tanaka
Polymyxin B (PMB) is a cationic cyclic peptide that can selectively inhibit the growth of Gram-negative bacteria by disrupting the outer membrane permeability barrier through binding to lipopolysaccharide (LPS). Here, a fluorescent PMB derivative (PMB-Ds) was applied to visually confirm the vacuole as a direct lethal target of PMB against fungal cells, which lack LPS. PMB-Ds could be visualized in the normal rounded vacuolar membrane of Saccharomyces cerevisiae cells, suggesting the presence of a molecular ligand assisting the vacuole-targeting mobilization of the peptide in the organism...
April 2017: Microbiology
https://www.readbyqxmd.com/read/28441858/-development-of-an-eosinophilic-bronchitis-mouse-model-and-the-effects-of-eosinophil-activation-on-airway-hyperresponsiveness-in-eosinophilic-bronchitis-mice
#13
L Li, J T Lin
Objective: To develop a mouse model of eosinophilic bronchitis, and explore the effects of eosinophil activation on airway hyperresponsiveness. Methods: A total of 60 female specific pathogen free BALB/c female mice were divided randomly into four groups: polymyxin B group, normal saline group, polymyxin B+ N-methionine leucine phenylalanine (fMLP) group, normal saline+ fMLP group. All the groups were given corresponding nasal drops for 21 days. The former two groups were given 12 μl 0.5% polymyxin B or normal saline once a day by transnasal administration respectively...
April 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28438930/in-vitro-assessment-of-combined-polymyxin-b-and-minocycline-therapy-against-klebsiella-pneumoniae-carbapenemase-kpc-producing-k-pneumoniae
#14
Dennis Huang, Brenda Yu, John K Diep, Rajnikant Sharma, Michael Dudley, Keith S Kaye, Jason M Pogue, Cely Abboud Saad, Gauri Rao
The multi-drug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes have been reported with intravenous minocycline-based combination treatments for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416554/in-vitro-study-of-isapl1-mediated-mobilization-of-the-colistin-resistance-gene-mcr-1
#15
Laurent Poirel, Nicolas Kieffer, Patrice Nordmann
The plasmid-mediated mcr-1 gene encodes a phosphoethanolamine transferase conferring resistance to polymyxins. The mcr-1 gene is associated with insertion sequence ISApl1 (IS30 family). In-vitro mobilization assays demonstrated the functionality of the composite transposon structure ISApl1-mcr-1-ISApl1 Transposition generated a 2-bp duplication and occurred in AT-rich DNA regions. This is the first report demonstrating the mobility of the mcr-1 gene by transposition.
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416543/potential-toxicity-of-polymyxins-in-human-lung-epithelial-cells
#16
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
#17
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
#18
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
#19
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/28384882/polymyxin-b-induced-diffuse-cutaneous-hyperpigmentation
#20
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
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