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Multidrug resistant gram negative bacteria

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https://www.readbyqxmd.com/read/28306563/antimicrobial-resistant-gram-negative-infections-in-neonates-burden-of-disease-and-challenges-in-treatment
#1
Laura Folgori, Julia Bielicki, Paul T Heath, Mike Sharland
PURPOSE OF REVIEW: This review summarizes the main challenges of antimicrobial resistance (AMR) in the neonatal population with a special focus on multidrug-resistant (MDR) Gram-negative pathogens. RECENT FINDINGS: MDR-Gram-negative bacteria are a great concern in the neonatal population, with a worldwide rise in the reported incidence and with very limited therapeutic options. Extended-spectrum β-lactamase and carbapenem-resistant Enterobacteriaceae (CRE) have been reported as responsible for neonatal ICU outbreaks...
March 16, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28302397/structure-based-discovery-of-lpxc-inhibitors
#2
Jing Zhang, Audrey Chan, Blaise Lippa, Jason B Cross, Christopher Liu, Ning Yin, Jan Antoinette C Romero, Jonathan Lawrence, Ryan Heney, Prudencio Herradura, Jennifer Goss, Cynthia Clark, Cassandra Abel, Yanzhi Zhang, Katherine M Poutsiaka, Felix Epie, Mary Conrad, Azard Mahamoon, Kien Nguyen, Ajit Chavan, Edward Clark, Tong-Chuan Li, Robert K Cheng, Michael Wood, Ole A Andersen, Mark Brooks, Jason Kwong, John Barker, Ian Barrie Parr, Yugui Gu, M Dominic Ryan, Scott Coleman, Chester A Metcalf
The emergence and spread of multidrug-resistant (MDR) Gram negative bacteria presents a serious threat for public health. Novel antimicrobials that could overcome the resistance problems are urgently needed. UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase (LpxC) is a cytosolic zinc-based deacetylase that catalyzes the first committed step in the biosynthesis of lipid A, which is essential for the survival of Gram-negative bacteria. Our efforts toward the discovery of novel LpxC inhibitors are presented herein...
March 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28296174/vestibulotoxicity-with-systemic-gentamicin-in-different-dosing-regimens-our-experience-in-46-patients
#3
Mohammed Iqbal Syed, Jerome A Leis, Ophir Ilan, Wayne L Gold, David D Pothier, John A Rutka
Although the use of topical gentamicin has declined systemic gentamicin remains an important antimicrobial agent in the management of infections caused by multidrug-resistant gram-negative bacteria. Nephrotoxicity and Ototoxicity from systemic gentamicin is well documented despite normal gentamicin levels (peak and trough) and normal renal function tests Nephrotoxicity is a predisposing factor for vestibulotoxicity however vestibulotoxicity can still occur, in patients without nephrotoxicity [19 of 46 (43.1%) % in our series] much more significantly in single daily dosing (SDD) compared to multiple daily dosing (MDD) From our database of 46 patients we analyzed 19 patients with vestibulotoxicity without nephrotoxicity...
March 11, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28291943/a-new-combination-of-a-pleuromutilin-derivative-and-doxycycline-for-treatment-of-multidrug-resistant-acinetobacter-baumannii
#4
Shajila Siricilla, Katsuhiko Mitachi, Junshu Yang, Shakiba Eslamimehr, Maddie R Lemieux, Bernd Meibohm, Yinduo Ji, Michio Kurosu
Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most difficult Gram-negative bacteria to treat and eradicate. In a cell-based screening of pleuromutilin derivatives against a drug sensitive A. baumannii strain (ATCC 19606), new molecules (2-4) exhibit bacteriostatic activity with 3.13 μg/mL concentration and 1 shows bactericidal activity with an MBC of 6.25 μg/mL. The pleuromutilin derivative 1 displays strong synergistic effects with doxycycline in a wide range of concentrations. A 35/1 ratio of 1 and doxycycline (1-Dox35/1) kills drug susceptible A...
March 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28289407/a-novel-antimicrobial-endolysin-lyspa26-against-pseudomonas-aeruginosa
#5
Mingquan Guo, Chunyan Feng, Jie Ren, Xuran Zhuang, Yan Zhang, Yongzhang Zhu, Ke Dong, Ping He, Xiaokui Guo, Jinhong Qin
The global increase in multidrug resistant (MDR) bacteria has led to phage therapy being refocused upon. A novel endolysin, LysPA26, containing a lysozyme-like domain, was screened against Pseudomonas aeruginosa in this study. It had activity against MDR P. aeruginosa without pretreatment with an outer-membrane permeabilizer. LysPA26 could kill up to 4 log units P. aeruginosa in 30 min. In addition, temperature and pH effect assays revealed that LysPA26 had good stability over a broad range of pH and temperatures...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28288860/epidemiology-of-multidrug-resistant-gram-negative-pathogens-isolated-from-ventilator-associated-pneumonia-in-icu-patients
#6
Richa Gupta, Abida Malik, Meher Rizvi, Moied Ahmed, Anuradha Singh
OBJECTIVES: Antibiotic resistance among Gram-negative pathogens isolated from ventilator-associated pneumonia (VAP) poses a grave threat in intensive care unit (ICU) patients. The aim of this study was to assess the prevalence of pathogens in ICU patients and their drug resistance profile. The prevalence of extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases and metallo-β-lactamases (MBLs) was also assessed. METHODS: Tracheal aspirates were collected aseptically from 87 ICU patients between May 2012 and January 2014...
March 10, 2017: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/28280277/preparation-and-antimicrobial-evaluation-of-polyion-complex-pic-nanoparticles-loaded-with-polymyxin-b
#7
Ignacio Insua, Sieta Majok, Anna F A Peacock, Anne Marie Krachler, Francisco Fernandez-Trillo
Here, we describe novel polyion complex (PIC) particles for the delivery of Polymyxin B (Pol-B), an antimicrobial peptide currently used in the clinic as a last resort antibiotic against multidrug-resistant gram-negative bacteria. A range of conditions for the controlled assembly of Pol-B with poly(styrene sulphonate) (PSS) has been identified which let us prepare stable colloidal PIC particles. This way, PIC particles containing different Pol-B:PSS ratios have been prepared and their stability under simulated physiological conditions (i...
February 2017: European Polymer Journal
https://www.readbyqxmd.com/read/28275006/polymyxins-antibacterial-activity-susceptibility-testing-and-resistance-mechanisms-encoded-by-plasmids-or-chromosomes
#8
REVIEW
Laurent Poirel, Aurélie Jayol, Patrice Nordmann
SUMMARYPolymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria...
April 2017: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/28273820/in-vitro-activities-of-lcb-01-0648-a-novel-oxazolidinone-against-gram-positive-bacteria
#9
Sang-Hun Oh, Josep Kim, Sung-Yoon Baek, Sang-Eun Chae, Hee-Soo Park, Young-Lag Cho, Jin-Hwan Kwak
Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria...
March 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28270957/prevalence-of-uropathogen-and-their-antibiotic-resistance-pattern-among-diabetic-patients
#10
Demiss Nigussie, Anteneh Amsalu
OBJECTIVE: Diabetes mellitus (DM) and antibiotic resistance is an emerging public health problem in Ethiopia. Urinary tract infections (UTIs) are common and occasionally life-threatening condition among diabetic patients. Despite, all these problems, antibiotics are prescribed empirically which may adversely affect antibiotic resistance so far. Therefore the aim of this study was to identify the etiologic agents of UTI and their antibiotic resistance pattern among diabetic patients attending diabetic clinic of Hawassa University Referral Hospital...
March 2017: Turkish Journal of Urology
https://www.readbyqxmd.com/read/28264618/assessment-of-early-combination-effects-of-colistin-and-meropenem-against-pseudomonas-aeruginosa-and-acinetobacter-baumannii-in-dynamic-time-kill-experiments
#11
Thomas Tängdén, Matti Karvanen, Lena E Friberg, Inga Odenholt, Otto Cars
BACKGROUND: In view of the paucity of clinical evidence, in vitro studies are needed to find antibiotic combinations effective against multidrug-resistant Gram-negative bacteria. Interpretation of in vitro effects is usually based on bacterial growth after 24 h in time-kill and checkerboard experiments. However, the clinical relevance of the effects observed in vitro is not established. In this study we explored alternative output parameters to assess the activities of colistin and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii...
March 6, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28263303/pentamidine-sensitizes-gram-negative-pathogens-to-antibiotics-and-overcomes-acquired-colistin-resistance
#12
Jonathan M Stokes, Craig R MacNair, Bushra Ilyas, Shawn French, Jean-Philippe Côté, Catrien Bouwman, Maya A Farha, Arthur O Sieron, Chris Whitfield, Brian K Coombes, Eric D Brown
The increasing use of polymyxins(1) in addition to the dissemination of plasmid-borne colistin resistance threatens to cause a serious breach in our last line of defence against multidrug-resistant Gram-negative pathogens, and heralds the emergence of truly pan-resistant infections. Colistin resistance often arises through covalent modification of lipid A with cationic residues such as phosphoethanolamine-as is mediated by Mcr-1 (ref. 2)-which reduce the affinity of polymyxins for lipopolysaccharide(3). Thus, new strategies are needed to address the rapidly diminishing number of treatment options for Gram-negative infections(4)...
March 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28258237/computational-modelling-of-efflux-pumps-and-their-inhibitors
#13
REVIEW
Venkata Krishnan Ramaswamy, Pierpaolo Cacciotto, Giuliano Malloci, Attilio V Vargiu, Paolo Ruggerone
Antimicrobial resistance is based on the multifarious strategies that bacteria adopt to face antibiotic therapies, making it a key public health concern of our era. Among these strategies, efflux pumps (EPs) contribute significantly to increase the levels and profiles of resistance by expelling a broad range of unrelated compounds - buying time for the organisms to develop specific resistance. In Gram-negative bacteria, many of these chromosomally encoded transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component...
February 28, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28257182/poly-carboxylic-acid-cyclodextrin-anionic-porphyrin-finished-fabrics-as-photosensitizer-releasers-for-antimicrobial-photodynamic-therapy
#14
Maria Angela Castriciano, Roberto Zagami, Maria Pia Casaletto, Bernard Martel, Mariachiara Trapani, Andrea Romeo, Valentina Villari, Maria Teresa Sciortino, Laura Grasso, Salvatore Guglielmino, Luigi Monsù Scolaro, Antonino Mazzaglia
In the development of new antibacterial therapeutic approaches to fight multidrug-resistant bacteria, antimicrobial photodynamic therapy (aPDT) represents a well-known alternative to treat local infections caused by different microorganisms. Here we present a polypropylene (PP) fabric finished with citrate-hydroxypropyl-βCD polymer (PP-CD) entrapping the tetra-anionic 5,10,15,20-tetrakis(4-sulfonatophenyl)-21H,23H-porphine (TPPS) as photosensitizer-eluting scaffold (PP-CD/TPPS) for aPDT. The concept is based on host-guest complexation of porphyrin in the cavities of CDs immobilized on the PP fibers, followed by its sustained and controlled delivery in release medium and simultaneous photoinactivation of microorganisms...
March 20, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28254253/surveillance-culture-for-multidrug-resistant-gram-negative-bacteria-performance-in-liver-transplant-recipients
#15
Maristela Pinheiro Freire, Isabel Cristina Villela Soares Oshiro, Patrícia Rodrigues Bonazzi, Ligia Câmera Pierrotti, Larissa Marques de Oliveira, Anna Silva Machado, Inneke Marie Van Der Heijdenn, Flavia Rossi, Silvia Figueiredo Costa, Luiz Augusto Carneiro D'Albuquerque, Edson Abdala
BACKGROUND: The prevalence of infection with multidrug-resistant gram-negative bacteria (MDR-GNB) after solid-organ transplantation is increasing. Surveillance culture (SC) seems to be an important tool for MDR-GNB control. The goal of this study was to analyze the performance of SC for MDR-GNB among liver transplant (LT) recipients. METHODS: This was a prospective cohort study involving patients who underwent LT between November 2009 and November 2011. We screened patients for extended spectrum β-lactamase-producing Escherichia coli, extended spectrum β-lactamase-producing Klebsiella pneumoniae, and carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB)...
March 1, 2017: American Journal of Infection Control
https://www.readbyqxmd.com/read/28251730/epidemiological-surveillance-of-multidrug-resistant-gram-negative-bacteria-in-a-solid-organ-transplantation-department
#16
Anastasia Geladari, Theodoros Karampatakis, Charalampos Antachopoulos, Elias Iosifidis, Olga Tsiatsiou, Lida Politi, Aggeliki Karyoti, Vasilios Papanikolaou, Athanassios Tsakris, Emmanuel Roilides
BACKGROUND: We assessed the impact of intensified infection control measures (ICM) on colonization and infection caused by carbapenem-resistant (CR) Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii in a Solid Organ Transplantation (SOT) Department. METHODS: A quasi-experimental methodology was followed. The study was divided in 3 periods: pre-intervention, intervention with implementation of an ICM bundle including active surveillance program (ASP) and gradually enhanced measures, and post-ASP without ASP...
March 2, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28249575/first-report-on-bla-ndm-1-producing-acinetobacter-baumannii-in-three-clinical-isolates-from-ethiopia
#17
Michael Pritsch, Ahmed Zeynudin, Maxim Messerer, Simon Baumer, Gabriele Liegl, Soeren Schubert, Thomas Löscher, Michael Hoelscher, Tefara Belachew, Andrea Rachow, Andreas Wieser
BACKGROUND: Multidrug-resistant Gram-negative bacterial infections are recognized as one of the major threats to global health. In this study, we describe for the first time bla NDM-1 gene carrying organisms from Ethiopia consisting of three Acinetobacter baumannii isolates from patients in Jimma. METHODS: Besides phenotypic antimicrobial susceptibility testing, molecular strain typing and sequencing was performed to describe the phylogenetic relation of the Ethiopian isolates in detail in relation to published isolates from all over the globe...
March 1, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28248002/amino-acid-block-copolymers-with-broad-antimicrobial-activity-and-barrier-properties
#18
Michael P Bevilacqua, Daniel J Huang, Brian D Wall, Shalyn J Lane, Carl K Edwards, Jarrod A Hanson, Diego Benitez, Joseph S Solomkin, Timothy J Deming
Antimicrobial properties of a long-chain, synthetic, cationic, and hydrophobic amino acid block copolymer are reported. In 5 and 60 min time-kill assays, solutions of K100 L40 block copolymers (poly(l-lysine·hydrochloride)100 -b-poly(l-leucine)40 ) at concentrations of 10-100 µg mL(-1) show multi-log reductions in colony forming units of Gram-positive and Gram-negative bacteria, as well as yeast, including multidrug-resistant strains. Driven by association of hydrophobic segments, K100 L40 copolymers form viscous solutions and self-supporting hydrogels in water at concentrations of 1 and 2 wt%, respectively...
March 1, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28246361/new-mouse-model-for-chronic-infections-by-gram-negative-bacteria-enabling-the-study-of-anti-infective-efficacy-and-host-microbe-interactions
#19
Daniel Pletzer, Sarah C Mansour, Kelli Wuerth, Negin Rahanjam, Robert E W Hancock
Only a few, relatively cumbersome animal models enable long-term Gram-negative bacterial infections that mimic human situations, where untreated infections can last for weeks. Here, we describe a simple murine cutaneous abscess model that enables chronic or progressive infections, depending on the subcutaneously injected bacterial strain. In this model, Pseudomonas aeruginosa cystic fibrosis epidemic isolate LESB58 caused localized high-density skin and soft tissue infections and necrotic skin lesions for up to 10 days but did not disseminate in either CD-1 or C57BL/6 mice...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28242660/wck-5222-cefepime-zidebactam-antimicrobial-activity-tested-against-clinical-isolates-of-gram-negative-bacteria-collected-worldwide-2015
#20
Helio S Sader, Mariana Castanheira, Michael Huband, Ronald N Jones, Robert K Flamm
WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of Enterobacteriaceae (5, 946), Pseudomonas aeruginosa (1, 291) and Acinetobacter spp. (639) from the United States (2, 919), Europe (3, 004), Asia-Pacific (1, 370) and Latin America (583). The isolates were susceptibility tested by reference broth microdilution method against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents...
February 27, 2017: Antimicrobial Agents and Chemotherapy
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