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https://www.readbyqxmd.com/read/29784845/interaction-of-bacterial-phenazines-with-colistimethate-in-bronchial-epithelial-cells
#1
Valeri V Mossine, Deborah L Chance, James K Waters, Thomas P Mawhinney
Multidrug-resistant bacterial infections are being increasingly treated in clinics with polymyxins, a class of antibiotics associated with adverse effects in the kidney, nervous system, or airways of a significant proportion of human and animal patients. Although many of the resistant pathogens display enhanced virulence, a hazard of cytotoxic interactions between polymyxin antibiotics and bacterial virulence factors (VFs) has not been assessed, to date. We report here on testing paired combinations of four Pseudomonas aeruginosa VF phenazine toxins, pyocyanin (PYO), 1-hydroxyphenazine (1-HP), phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), and two commonly prescribed polymyxin drugs, colistimethate (CMS)/colistin and polymyxin B, in three human airway cell lines, BEAS-2B, HBE-1, and CFT-1...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29782237/effect-of-porins-and-bla-kpc-expression-on-activity-of-imipenem-with-relebactam-in-klebsiella-pneumoniae-can-antibiotic-combinations-overcome-resistance
#2
Gregory Balabanian, Michael Rose, Nyla Manning, David Landman, John Quale
Imipenem with relebactam is a novel β-lactam-β-lactamase inhibitor that has activity against most KPC-producing Enterobacteriaceae. Using 10 isolates of KPC-possessing Klebsiella pneumoniae, we assessed the relationship between imipenem-relebactam minimum inhibitory concentrations (MICs) and mechanisms known to contribute to antimicrobial resistance. The effect of adding a second agent was assessed by time-kill experiments. Mutations affecting the genes encoding porins ompK35 and ompK36 and identification of β-lactamases were assessed by PCR...
May 21, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29774093/distribution-of-virulence-associated-genes-and-antimicrobial-susceptibility-in-clinical-acinetobacter-baumannii-isolates
#3
Chao Liu, Yaowen Chang, Ying Xu, Yun Luo, Linrong Wu, Zhanjun Mei, Shigang Li, Rui Wang, Xu Jia
Acinetobacter baumannii is undoubtedly one of the most clinically significant pathogens. The multidrug resistance and virulence potential of A. baumannii are responsible for hospital-acquired nosocomial infections. Unlike numerous investigations on the drug-resistant epidemiology of A. baumanni , virulence molecular epidemiology is less studied. Here, we collected 88 A. baumannii clinical isolates, tested their antimicrobial susceptibility to 10 commonly used antibiotics and analyzed the distribution of 9 selected virulence-associated genes, aims to investigate the primary characteristics of the virulence-associated genes that exist in clinically multidrug resistant (MDR) and non-MDR isolates of A...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29760690/two-new-lytic-bacteriophages-of-the-myoviridae-family-against-carbapenem-resistant-acinetobacter-baumannii
#4
Weilong Zhou, Yu Feng, Zhiyong Zong
Two lytic bacteriophages, WCHABP1 and WCHABP12, were recovered from hospital sewage and were able to infect 9 and 12 out of 18 carbapenem-resistant Acinetobacter baumannii clinical strains, which belonged to different clones. Electron microscopy scan showed that both bacteriophages had the similar morphology as those of the Myoviridae family. Whole genomic sequencing revealed 45.4- or 45.8-kb genome with a 37.6% GC content for WCHABP1 and WCHABP12, both of which showed significant DNA sequence similarity with bacteriophages of the Ap22virus genus within the Myoviridae family...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29760144/personalizing-polymyxin-b-dosing-using-an-adaptive-feedback-control-algorithm
#5
Elizabeth A Lakota, Cornelia B Landersdorfer, Roger L Nation, Jian Li, Keith S Kaye, Gauri G Rao, Alan Forrest
Polymyxin B is used as an antibiotic of last resort for patients with multidrug-resistant Gram-negative bacterial infections; however, it carries a significant risk of nephrotoxicity. Herein we present a polymyxin B therapeutic window based on target area under the concentration-time curve (AUC) values and an adaptive feedback control algorithm (algorithm) which allows for the personalization of polymyxin B dosing. The upper bound of this therapeutic window was determined through a pharmacometric meta-analysis of polymyxin B nephrotoxicity data, and the lower bound was derived from murine thigh-infection pharmacokinetic/pharmacodynamic studies...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29760138/co-location-of-the-polymyxin-resistance-gene-mcr-1-and-variant-of-mcr-3-on-a-plasmid-in-escherichia-coli-from-chicken-farm
#6
Rong Xiang, Bi-Hui Liu, An-Yun Zhang, Chang-Wei Lei, Xiao-Lan Ye, Yan-Xian Yang, Yan-Peng Chen, Hong-Ning Wang
A colistin-resistant Escherichia coli from commercial poultry farm in China carried two colistin-resistance genes mcr-1 and variant of mcr-3 in an IncP plasmid. The variant of mcr-3 gene, named mcr-3.11 , encoded two amino acid substitutions compared with the mcr-3 A novel genetic structure, IS Kpn40-mcr-3-dgkA - IS Kpn40 , might be the key element mediating translocation of mcr-3 through the formation of circular form. The mcr-1 and mcr-3 genes co-located on a plasmid might pose huge threat to public health...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29758020/defining-icr-mo-an-intrinsic-colistin-resistance-determinant-from-moraxella-osloensis
#7
Wenhui Wei, Swaminath Srinivas, Jingxia Lin, Zichen Tang, Shihua Wang, Saif Ullah, Vishnu Goutham Kota, Youjun Feng
Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family...
May 14, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29755727/antimicrobial-resistance-profile-of-e-coli-isolated-from-raw-cow-milk-and-fresh-fruit-juice-in-mekelle-tigray-ethiopia
#8
Haftay Abraha Tadesse, Netsenet Berhe Gidey, Kidane Workelule, Hagos Hailu, Seyfe Gidey, Abrha Bsrat, Habtamu Taddele
Aim: Foodborne illnesses represent a public health problem in developed and developing countries. They cause great suffering and are transmitted directly or indirectly between animals and humans and circulate in the global environment . E. coli are among them, causing a major public health problem. The aim of this study was therefore to study the antimicrobial resistance profile of E. coli from raw cow milk and fruit juice. Materials and Methods: A cross-sectional study was conducted from October 2016 to June 2017 on 258 samples collected from milk shops ( n = 86), dairy farms ( n = 86), and fruit juice ( n = 86) in different subcities of Mekelle...
2018: Veterinary Medicine International
https://www.readbyqxmd.com/read/29739882/gene-expression-kinetics-governs-stimulus-specific-decoration-of-the-salmonella-outer-membrane
#9
Xinyu Hong, H Deborah Chen, Eduardo A Groisman
Lipid A is the innermost component of the lipopolysaccharide (LPS) molecules that occupy the outer leaflet of the outer membrane in Gram-negative bacteria. Lipid A is recognized by the host immune system and targeted by cationic antimicrobial compounds. In Salmonella enterica serovar Typhimurium, the phosphates of lipid A are chemically modified by enzymes encoded by targets of the transcriptional regulator PmrA. These modifications increase resistance to the cationic peptide antibiotic polymyxin B by reducing the negative charge of the LPS...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29730830/the-epidemiology-evolution-and-treatment-of-kpc-producing-organisms
#10
REVIEW
Ann Marie Porreca, Kaede V Sullivan, Jason C Gallagher
PURPOSE OF REVIEW: The purpose of this review is to investigate the evolution and epidemiology of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms and the current and future treatment options for infections caused by KPC-producing isolates. RECENT FINDINGS: The emergence of resistance in Enterobacteriaceae producing carbapenemases globally has increased the challenges in treating infections caused by these organisms. One of the prominent mechanisms of resistance is the production of KPC enzymes...
May 5, 2018: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/29720352/bacteremia-and-meningitis-caused-by-oxa-23-producing-acinetobacter-baumannii-molecular-characterization-and-susceptibility-testing-for-alternative-antibiotics
#11
Kamile Francine Schuertz, Felipe Francisco Tuon, Jussara Kasuko Palmeiro, Danieli Conte, João Paulo Marochi Telles, Lucas Eduardo Trevisoli, Libera Maria Dalla-Costa
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii infection is a concern in developing countries due to high incidence, few therapeutic options, and increasing costs. OBJECTIVE: Characterize and analyze the antibiotic susceptibility patterns of carbapenem-resistant A. baumannii isolates and evaluate clinical data of meningitis and bacteremia caused by this microorganism. METHODS: Twenty-six A. baumannii isolates from 23 patients were identified by MALDI-TOF and automated methods and genotyped using pulsed field genotyping electrophoresis...
April 24, 2018: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/29720043/antimicrobial-stewardship-through-telemedicine-and-its-impact-on-multi-drug-resistance
#12
Rodrigo P Dos Santos, Camila H Dalmora, Stephani A Lukasewicz, Otávio Carvalho, Caroline Deutschendorf, Raquel Lima, Tiago Leitzke, Nilson C Correa, Marcelo V Gambetta
Introduction Telemedicine technologies are increasingly being incorporated into infectious disease practice. We aimed to demonstrate the impact of antimicrobial stewardship through telemedicine on bacterial resistance rates. Methods We conducted a quasi-experimental study in a 220-bed hospital in southern Brazil. An antimicrobial stewardship program incorporating the use of telemedicine was implemented. Resistance and antimicrobial consumption rates were determined and analysed using a segmented regression model...
January 1, 2018: Journal of Telemedicine and Telecare
https://www.readbyqxmd.com/read/29713282/synergistic-killing-of-polymyxin-b-in-combination-with-the-antineoplastic-drug-mitotane-against-polymyxin-susceptible-and-resistant-acinetobacter-baumannii-a-metabolomic-study
#13
Thien B Tran, Phillip J Bergen, Darren J Creek, Tony Velkov, Jian Li
Polymyxins are currently used as the last-resort antibiotics against multidrug-resistant Acinetobacter baumannii . As resistance to polymyxins emerges in A. baumannii with monotherapy, combination therapy is often the only remaining treatment option. A novel approach is to employ the combination of polymyxin B with non-antibiotic drugs. In the present study, we employed metabolomics to investigate the synergistic mechanism of polymyxin B in combination with the antineoplastic drug mitotane against polymyxin-susceptible and -resistant A...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29706941/novel-polymyxin-combination-with-antineoplastic-mitotane-improved-the-bacterial-killing-against-polymyxin-resistant-multidrug-resistant-gram-negative-pathogens
#14
Thien B Tran, Jiping Wang, Yohei Doi, Tony Velkov, Phillip J Bergen, Jian Li
Due to limited new antibiotics, polymyxins are increasingly used to treat multidrug-resistant (MDR) Gram-negative bacteria, in particular carbapenem-resistant Acinetobacter baumannii , Pseudomonas aeruginosa , and Klebsiella pneumoniae . Unfortunately, polymyxin monotherapy has led to the emergence of resistance. Polymyxin combination therapy has been demonstrated to improve bacterial killing and prevent the emergence of resistance. From a preliminary screening of an FDA drug library, we identified antineoplastic mitotane as a potential candidate for combination therapy with polymyxin B against polymyxin-resistant Gram-negative bacteria...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29701307/exogenous-fatty-acids-alter-phospholipid-composition-membrane-permeability-capacity-for-biofilm-formation-and-antimicrobial-peptide-susceptibility-in-klebsiella-pneumoniae
#15
Chelsea R Hobby, Joshua L Herndon, Colton A Morrow, Rachel E Peters, Steven J K Symes, David K Giles
Klebsiella pneumoniae represents a major threat to human health due to a combination of its nosocomial emergence and a propensity for acquiring antibiotic resistance. Dissemination of the bacteria from its native intestinal location creates severe, complicated infections that are particularly problematic in healthcare settings. Thus, there is an urgency for identifying novel treatment regimens as the incidence of highly antibiotic-resistant bacteria rises. Recent findings have highlighted the ability of some Gram-negative bacteria to utilize exogenous fatty acids in ways that modify membrane phospholipids and influence virulence phenotypes, such as biofilm formation and antibiotic resistance...
April 27, 2018: MicrobiologyOpen
https://www.readbyqxmd.com/read/29688451/genome-scale-metabolic-modeling-of-responses-to-polymyxins-in-pseudomonas-aeruginosa
#16
Yan Zhu, Tobias Czauderna, Jinxin Zhao, Matthias Klapperstueck, Mohd Hafidz Mahamad Maifiah, Mei-Ling Han, Jing Lu, Björn Sommer, Tony Velkov, Trevor Lithgow, Jiangning Song, Falk Schreiber, Jian Li
Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients, and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was used to analyze bacterial metabolic changes at the systems level...
April 1, 2018: GigaScience
https://www.readbyqxmd.com/read/29686149/retained-activity-of-an-o25b-specific-monoclonal-antibody-against-mcr-1-producing-escherichia-coli-st131
#17
Luis M Guachalla, Katharina Ramoni, Cecilia Varga, Michele Mutti, Akela Ghazawi, Tibor Pál, Eszter Nagy, Ágnes Sonnevend, Gábor Nagy, Valéria Szijártó
Plasmid-encoded colistin resistance is emerging among extra-intestinal pathogenic Escherichia coli including the epidemic clone ST131-H30. Mcr-1 transfers a phosphoethanolamine to the lipid A portion of LPS conferring resistance to polymyxins. We investigated whether this modification changed the activity of the monoclonal antibody, ASN-4 specific to the O25b side-chain of ST131 LPS. We confirmed that, unlike colistin, ASN-4 retained its bactericidal and endotoxin neutralizing activity and therefore offer a treatment option against extremely drug-resistant ST131 isolates...
April 23, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29677485/octapeptins-lipopeptide-antibiotics-against-multidrug-resistant-superbugs
#18
Antoine Abou Fayad, Jennifer Herrmann, Rolf Müller
Antimicrobial resistance is increasing at an alarming rate. Polymyxin, one of the few antibiotics of last resort, is heavily affected. In this issue of Cell Chemical Biology, Velkov et al. (2018) present a promising alternative: octapeptin lipopeptide antibiotics active against multidrug- and extensively drug-resistant Gram-negative bacteria, which might help overcoming resistance toward polymyxins.
April 19, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29674129/polymyxin-b-etest%C3%A2-compared-to-gold-standard-broth-microdilution-in-carbapenem-resistant-enterobacteriaceae-exhibiting-a-wide-range-of-polymyxin-b-mics
#19
Brandon Kulengowski, Julie A Ribes, David S Burgess
OBJECTIVES: Polymyxins have been revitalized to combat carbapenem-resistant Enterobacteriaceae (CRE). However, evaluating the activity of these agents by traditional broth dilution methods is not practical for busy clinical laboratories. We compared polymyxin B (PMB) activity utilizing two quantitative susceptibility testing methods, Etest® and broth microdilution (BMD), against CRE isolates from patients at an academic medical center. METHODS: PMB activity against 70 CRE clinical isolates was determined by EtestP® P according to manufacturer and by BMD according to CLSI guidelines...
April 16, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29673980/photoactivated-2-3-distyrylindoles-kill-multi-drug-resistant-bacteria
#20
Leslie Edwards, Danielle Turner, Cody Champion, Megha Khandelwal, Kailee Zingler, Cassidy Stone, Ruwini D Rajapaksha, Jing Yang, Mahinda I Ranasinghe, Alexander Kornienko, Liliya V Frolova, Snezna Rogelj
Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1 μM, the lead compound 1 completely (ca. 109  CFU/mL) eradicated such Gram-positive organisms as S. aureus (MRSA, MSSA), E. faecalis (VRE), S. pyogenes and S. mutans when irradiated with white light for 2 min. At the concentration of 5 μM and in the presence of polymyxin E at non-bactericidal 1.25 μg/mL concentration, 1 also showed a 7-log to 9-log reductions in bacterial counts of such Gram-negative organisms as multi-drug resistant (MDR) A...
April 3, 2018: Bioorganic & Medicinal Chemistry Letters
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