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Antibacterial resistance

Ling Gui Ning, En-Tang Kang, Yun Bing Wang, Xue Feng Hu, Li Qun Xu
Traditional use of antibiotics through injection or oral ingestion has many disadvantages, such as detrimental side effects in the host, less effectiveness, high and repeated doses, and development of drug resistance. For prevention and treatment of implant-associated infections, the continuous local delivery of antibiotics is required. Thus, there is a strong demand for the development of drug carrier systems to control the release of antibiotics in a moderate manner over an appropriate timescale. This review summarizes the carrier platforms used for the loading of antibiotics, and highlights their drug release behaviors as well as in vitro and in vivo antibacterial properties...
March 14, 2018: Current Pharmaceutical Design
Hui Ye
Antimicrobial peptides are derived from the viral fusion domain of influenza virus hemagglutinin based on rational analysis of the intermolecular interaction between peptides and bacterial outer membrane. It is revealed that the isolated viral fusion domain is a negatively charged peptide HAfp1-23 that cannot effectively interact with the anionic membrane. Conversion of the native HAfp1-23 to a positively charged peptide HAfp1-23 _KK by E11K/D19K mutation can promote the peptide-membrane interaction substantially; this confers to the peptide a moderate antibacterial potency against antibiotic-resistant bacterial strains...
March 2018: Journal of Peptide Science: An Official Publication of the European Peptide Society
Ronald Domalaon, Temilolu Idowu, George G Zhanel, Frank Schweizer
The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades...
April 2018: Clinical Microbiology Reviews
Hui Sun, Yuanxiu Hong, Yuejing Xi, Yijie Zou, Jingyi Gao, Jianzhong Du
Antimicrobial peptides (AMPs) have been attracting much attention due to their excellent antimicrobial efficiency and low rate in driving antimicrobial resistance (AMR) which has been increasing globally to alarming levels. Conjugation of AMPs into functional polymers not only preserves excellent antimicrobial activities but reduces the toxicity and offers more functionalities, which brings new insight towards developing multifunctional biomedical materials such as hydrogels, polymer vesicles, polymer micelles, etc...
March 14, 2018: Biomacromolecules
Thomas Germe, Judit Vörös, Frederic Jeannot, Thomas Taillier, Robert A Stavenger, Eric Bacqué, Anthony Maxwell, Benjamin D Bax
Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA ('poisoning') in an analogous fashion to fluoroquinolones, but without the requirement for the water-metal-ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase-DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate...
March 10, 2018: Nucleic Acids Research
James J Leyden, Vilma Sniukiene, David R Berk, Alexandre Kaoukhov
BACKGROUND: There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Khurram Muaz, Muhammad Riaz, Saeed Akhtar, Sungkwon Park, Amir Ismail
Poultry production is among the most rapidly growing industries around the globe, and poultry is one of the major sources of meat. Poultry farmers use disease preventive and growth promoter antibiotics for faster growth of chickens in the shortest possible time to increase the rate of feed assimilation and to lower the incidence of mortality caused by a pathogen attack. Antibiotics may result in dysfunctionality of beneficial gut microbiota and increase resistance among microbial pathogens in poultry. Residues of these antibiotics in poultry meat have been determined in many of the studies globally and are considered one of the possible causes of antibacterial resistance in human pathogens...
March 14, 2018: Journal of Food Protection
David F Driscoll
The incidence of antimicrobial resistance (AMR) worldwide is increasing as the pipeline for the development of new chemotherapeutic entities is decreasing. Clearly, overexposure to antibiotics, including excessive dosing, is a key factor that fuels AMR. In fact, most of the new antibacterial agents under development are derivatives of existing classes of antibiotics. Novel approaches involving unique antimicrobial combinations, targets, and/or delivery systems are under intense investigation. An innovative combination of active pharmaceutical ingredients (APIs) consisting of antimicrobial drug(s), krill-oil-based phospholipids, and omega-3 fatty acid triglycerides, that may extend the therapeutic viability of currently effective antibiotics, at least until new chemical entities are introduced, is described...
March 10, 2018: Antibiotics
P K Christova, N K Christov, P V Mladenov, R Imai
Expression of the TaMDC1 in transgenic tomato plants confer resistance to bacterial and fungal pathogens, as well as an insect pest and thus prove in planta function of the wheat cystatin. Cystatins are the polypeptides with cysteine proteinase inhibitory activities. Plant cystatins or phytocystatins are known to contribute to plant resistance against insect pests. Recently, increasing data proved that some of the phytocystatins also have antifungal activities in vitro. Here, we functionally characterized a wheat multidomain cystatin, TaMDC1, using in planta assays...
March 12, 2018: Plant Cell Reports
Shui Liu, Yonglin Zhou, Xiaodi Niu, Tingting Wang, Jiyun Li, Zhongjie Liu, Jianfeng Wang, Shusheng Tang, Yang Wang, Xuming Deng
The emergence of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1) in carbapenem-resistant Gram-negative pathogens is an increasing clinical threat. Here we report the discovery of an NDM-1 inhibitor, magnolol, through enzyme inhibition screening. We showed that magnolol significantly inhibited NDM enzyme activity (IC50  = 6.47 µg/mL), and it restored the activity of meropenem against Escherichia coli ZC-YN3, an NDM-1-producing E. coli isolate, in in vitro antibacterial activity assays. Magnolol lacked direct antibacterial activity, but compared with meropenem alone, it reduced the MICs of meropenem against E...
December 2018: Cell Death Discovery
Jordan R Smith, Juwon Yim, Seth Rice, Kyle Stamper, Razie Kebriaei, Michael J Rybak
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for healthcare-associated infections, and treatment options are limited. Tedizolid (TZD), is a novel, oxazolidinone antibiotic with activity against MRSA. Previously, daptomycin (DAP), has demonstrated synergy with other antibiotics against MRSA. We sought to determine the efficacy of the combination of TZD + DAP against MRSA in an in vitro model of simulated endocardial vegetations (SEVs). Methods: TZD simulations of 200 mg once daily and DAP simulations of 6-mg/kg and 10-mg/kg once daily were tested alone and in the combinations of TZD + DAP 6-mg/kg or DAP 10-mg/kg against two clinical strains of MRSA, 494 and 67...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Lin Lin, Xuefang Mao, Yanhui Sun, Haiying Cui
A new inhibitor to overcome the multi-drug resistance of MRSA was developed in this study. Artemisinin (ART) was encapsulated in beta-cyclodextrin (β-CD) in order to enhance the solubility of ART. The molecular encapsulation of ART was confirmed by using Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-Ray Diffraction (XRD), and nuclear magnetic resonance (1 H NMR) methods. The phase solubility study showed the relationship between ART solubility and β-CD concentration. The antibacterial activity of ART/β-CDs inclusion complexes (ART/β-CDs-IC) (20 mg/mL) against MRSA was distinguished, with the inhibition rate of 99...
March 9, 2018: Microbial Pathogenesis
Md Shahadat Hossan, Hassan Jindal, Sarah Maisha, Chandramathi Samudi Raju, Shamala Devi Sekaran, Veeranoot Nissapatorn, Fatima Kaharudin, Lim Su Yi, Teng Jin Khoo, Mohammed Rahmatullah, Christophe Wiart
CONTEXT: The resistance of bacteria to antibiotics is raising serious concern globally. Asian medicinal plants could improve the current treatment strategies for bacterial infections. The antibacterial properties of medicinal plants used by the Khyang tribe in Bangladesh have not been investigated. OBJECTIVE: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria...
December 2018: Pharmaceutical Biology
Sinosh Skariyachan, Meghna Manjunath, Nikhil Bachappanavar
Acinetobacter baumannii, an opportunistic pathogen, has become multi-drug resistant (MDR) to major classes of antibacterial and poses grave threat to public health. The current study focused to screen novel phytotherapeutics against prioritized targets of Acinetobacter baumannii by computational investigation. Fourteen potential drug targets were screened based on their functional role in various biosynthetic pathways and the three dimensional structures of nine targets were retrieved from Protein Data Bank and others were computationally predicted...
March 12, 2018: Journal of Biomolecular Structure & Dynamics
Isabel Lane, Ashley Bryce, Suzanne M Ingle, Alastair D Hay
Purpose: Antimicrobial resistance is a significant threat to public health. Diagnostic uncertainty is a key driver of antimicrobial prescribing. We sought to determine whether locally relevant, real-time syndromic or microbiological infection epidemiology can improve prescribing by reducing diagnostic uncertainty. Methods: Eligible studies investigated effects on primary care prescribing for common infections in Organisation For Economic Co-Operation And Development countries...
February 26, 2018: Family Practice
Ikram Daou, Najia Moukrad, Omar Zegaoui, Fouzia Rhazi Filali
In this study, ZnO-TiO2 nanoparticles were synthesized from three different precursors for ZnO (zinc acetate di-hydrate, zinc nitrate hexahydrate and zinc sulfate heptahydrate) and titanium (IV) isopropoxide for TiO2 . The prepared nanomaterials were calcined at 500 °C for 3 h and characterized by various physicochemical techniques such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and transmission electron microscopy, combined with energy dispersive X-ray spectroscopy (TEM-EDS)...
March 2018: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Kanika Thakur, Gajanand Sharma, Bhupinder Singh, Ashay Jain, Rajeev Tyagi, Sanjay Chhibber, Om P Katare
AIM: The aim of the current study was to investigate the therapeutic efficacy of cationic-charged bilayered nanoemulsion for topical delivery of fusidic acid in eradicating methicillin-resistant Staphylococcus aureus (MRSA) bacterial burn wound infection. MATERIALS & METHODS: The developed carriers were characterized for particle size, antibacterial activity, cell viability assay in HaCat cell lines, rheological profile, ex vivo and in vivo studies, namely, full thickness MRSA 33591 murine burn wound infection via topical route...
March 12, 2018: Nanomedicine
Roberta J Melander, Daniel V Zurawski, Christian Melander
While broad spectrum antibiotics play an invaluable role in the treatment of bacterial infections, there are some drawbacks to their use, namely selection for and spread of resistance across multiple bacterial species, and the detrimental effect they can have upon the host microbiome. If the causitive agent of the infection is known, the use of narrow-spectrum antibacterial agents has the potential to mitigate some of these issues. This review outlines the advantages and challenges of narrow-spectrum antibacterial agents, discusses the progress that has been made toward developing diagnostics to enable their use, and describes some of the narrow-spectrum antibacterial agents currently being investigated against some of the most clinically important bacteria including Clostridium difficile, Mycobacterium tuberculosis and several ESKAPE pathogens...
2018: MedChemComm
Faiza H Waghu, Shaini Joseph, Sanket Ghawali, Elvis A Martis, Taruna Madan, Kareenhalli V Venkatesh, Susan Idicula-Thomas
Antimicrobial peptides (AMPs) are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP) family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family...
2018: Frontiers in Microbiology
Alexander Q Cusumano, Joshua G Pierce
Herein, we report the synthesis and evaluation of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones as antibacterial agents against methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). Lead compound 38 showed minimum inhibitory concentrations (MICs) of 8 and 4 μg/mL against MRSA and MRSE, respectively. Furthermore, compound 38 displayed a MIC of 8-16 μg/mL against linezolid-resistant MRSA. These molecules, previously underexplored as antibacterial agents, serve as a new scaffold for antimicrobial development...
February 27, 2018: Bioorganic & Medicinal Chemistry Letters
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