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Aminoglycoside resistance

Yagya Prasad Subedi, Madher N AlFindee, Jon Y Takemoto, Cheng-Wei Tom Chang
Classical aminoglycoside antibiotics are obsolete or hampered by the emergence of drug resistant bacteria. Recent discoveries of antifungal amphiphilic kanamycins offer new strategies for reviving and repurposing these old drugs. A simple structural modification turns the clinically obsolete antibacterial kanamycin into an antifungal agent. Structure-activity relationship studies have led to the production of K20 , an antifungal kanamycin that can be mass-produced for uses in agriculture as well as in animals...
June 1, 2018: MedChemComm
Hassan A Hemeg
Multidrug-resistant Escherichia coli is one of the most important public health concern worldwide that can be transferred through the food of animal origin to human being causing serious infection. The genetic responsibility of such resistant genes (Plasmids, integrons, and transposons) can be easily transmitted from the resistant strain to another. Therefore, the main objectives of the study is the molecular characterization of the resistant Escherichia coli isolates recovered from food samples and human isolates collected from outpatient clinics, KSA especially the resistance strains against aminoglycoside resistance genes which are responsible for the resistance against gentamicin and the resistance caused β-lactamases genes...
July 2018: Saudi Journal of Biological Sciences
Rodrigo M Burgos, Mark J Biagi, Keith A Rodvold, Larry H Danziger
Meropenem/vaborbactam (M/V) represents the first carbapenem and β-lactamase inhibitor combination approved for treatment of cUTI, including pyelonephritis. Vaborbactam is a novel boronic acid, β-lactamase inhibitor with a high affinity for serine β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This combination, Vabomere™, was approved in August 2017 by the United States Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections (cUTI) in patients 18 years or older, including pyelonephritis, caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae species complex...
August 14, 2018: Expert Opinion on Drug Metabolism & Toxicology
Long Sun, Juan Xu, Fang He
OBJECTIVES: Escherichia coli is the leading cause of urinary tract infections worldwide. Carbapenemase producing clinical isolates leave few therapeutic options. Here we report the draft genome sequence of a NDM-5, CTX-M-15, and OXA-1 co-producing E. coli ST167: a multidrug-resistant strain isolated from urine sample of a male hospitalized patient diagnosed with intracranial injury from a traffic accident. METHODS: The genome of E. coli ECWJ1 was sequenced using the Illumina HiSeq™ 4000 platform...
August 10, 2018: Journal of Global Antimicrobial Resistance
Fernanda Almeida, Amanda Aparecida Seribelli, Marta Inês Cazentini Medeiros, Dália Dos Prazeres Rodrigues, Alessandro de MelloVarani, Yan Luo, Marc W Allard, Juliana Pfrimer Falcão
Whole genome sequencing (WGS) has been used as a powerful technology for molecular epidemiology, surveillance, identification of species and serotype, identification of the sources of outbreaks, among other purposes. In Brazil, there is relatively few epidemiological data on Salmonella. In this study, 90 Salmonella Typhimurium strains had their genome sequenced to uncover the diversity of Salmonella Typhimurium isolated from humans and food, between 1983 and 2013, from different geographic regions in Brazil based on single nucleotide polymorphism (SNP) analysis...
2018: PloS One
M Thwaites, D Hall, A Stoneburner, D Shinabarger, A W Serio, K M Krause, A Marra, C Pillar
Plazomicin is a next-generation aminoglycoside that was approved by the US FDA in June 2018 for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis due to Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Proteus mirabilis. Plazomicin is active against multi-drug resistant (MDR) Enterobacteriaceae, where combination therapy is often used to treat infections caused by these pathogens. To determine synergy with other antibiotics, plazomicin was combined with antibiotics in checkerboard assays against MDR Enterobacteriaceae, including isolates with resistance to aminoglycosides and β-lactams; 10 Escherichia coli isolates, 8 Klebsiella spp...
July 11, 2018: Diagnostic Microbiology and Infectious Disease
Akilah Murray, Mayank Aggarwal, Melissa Pinard, Daniela Vullo, Marianna Patrauchan, Claudiu T Supuran, Robert McKenna
Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative facultative anaerobe belonging to the Pseudomonadaceae family. It is a multi-drug resistant opportunistic human pathogen and a common cause of life-threatening nosocomial infections, and is a key bacterial agent in cystic fibrosis and endocarditis diseases. The bacterium exhibits intrinsic resistance to most antibacterial agents, including aminoglycosides and quinolones. Hence, the identification of new drug targets for P. aeruginosa are ongoing. PsCA3 is a β-class carbonic anhydrase (β-CA) catalyzing the reversible hydration of carbon dioxide to bicarbonate and represents a new class of antimicrobial target...
August 7, 2018: ChemMedChem
Zorica Nanovic, Biserka Kaeva-Jovkovska, Gorica Breskovska, Milena Petrovska
BACKGROUND: Global tuberculosis (TB) epidemic is being driven to an increasing extent by the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis complex (MTBC). We present a case of primary multidrug-resistant tuberculosis (MDR-TB), highlighting Macedonian MDR-TB management issues. CASE REPORT: A 39-year old previously healthy Caucasian male, with no previous history of TB or close contact to TB, was admitted in referral TB-hospital due to respiratory bleeding...
July 20, 2018: Open Access Macedonian Journal of Medical Sciences
Swapan K Banerjee, Jeffrey M Farber
Emergence of antimicrobial resistance (AMR) in foodborne bacteria is a growing concern worldwide. AMR surveillance is a key element in understanding the implications resulting from the use of antibiotics for therapeutic as well as prophylactic needs. The emergence and spread of AMR in foodborne human pathogens is an indirect health hazard. This surveillance study reports the trend and pattern of AMR detected in Vibrio species isolated from molluscs harvested in Canada, between 2006 and 2012, against 19 commonly used antibiotics...
August 6, 2018: Antimicrobial Agents and Chemotherapy
Jin Zou, Wenwen Zhang, Hongjie Zhang, Xiaohua Douglas Zhang, Bo Peng, Jun Zheng
Antibiotic resistance has become a global crisis. Studies on the mechanism of bacterial tolerance to antibiotics will not only increase our conceptual understanding of bacterial death but also provide potential targets for novel inhibitors. We screened a mutant library containing a full set of in-frame deletion mutants of Escherichia coli K-12 and identified 140 genes that possibly contribute to gentamicin tolerance. Deletion of ksgA increased the inhibition and killing potency against mid-log phase bacteria by aminoglycosides...
August 6, 2018: Antimicrobial Agents and Chemotherapy
Fernando Sanz-García, Sara Hernando-Amado, José Luis Martínez
Ceftazidime/avibactam is a combination of beta-lactam/beta-lactamases inhibitor, which use is restricted to some clinical cases including cystic fibrosis patients infected with multidrug resistant Pseudomonas aeruginosa, in which mutation is the main driver of resistance. This study aims to predict the mechanisms of mutation-driven resistance that are selected for when P. aeruginosa is challenged with either ceftazidime or ceftazidime/avibactam. For this purpose, P. aeruginosa PA14 was submitted to experimental evolution in the absence of antibiotics and in the presence of increasing concentrations of ceftazidime or ceftazidime/avibactam for 30 consecutive days...
August 6, 2018: Antimicrobial Agents and Chemotherapy
Jaime I Castillo, Marcin Równicki, Monika Wojciechowska, Joanna Trylska
A combination of antibacterial agents should make the emergence of resistance in bacteria less probable. Thus we have analyzed the synergistic effects between antibacterial antisense peptide nucleic acids (PNA) and conventional antibiotics against Escherichia coli AS19 (lipopolysaccharide defective) strain and a derivative of a pathogenic strain E. coli O157:H7. PNAs were designed to target mRNA transcripts encoding the essential acyl carrier protein (gene acpP) and conjugated to the cell-penetrating peptide (KFF)3 K for cellular uptake...
July 27, 2018: Bioorganic & Medicinal Chemistry Letters
Andrea Novelli
Antibiotic resistance and new drugs in urologic setting: what we need to know? Urinary tract infections (UTIs) are among the most frequent infectious diseases, and represent an important public health problem with a substantial economic burden. In recent years the chemoresistance of the main uropathogens has significantly increased worldwide. Extended spectrum beta-lactamase (ESBL) production and multi-drug resistant (MDR) clones of Escherichia coli and Klebsiella pneumoniae are limiting available treatment options...
July 2018: Urologia
Tanawan Soimala, Antina Lübke-Becker, Stefan Schwarz, Andrea T Feßler, Charlotte Huber, Torsten Semmler, Roswitha Merle, Heidrun Gehlen, Johanna C Eule, Birgit Walther
Severe infections due to methicillin-resistant Staphylococcus aureus (MRSA) have been increasingly recognized in virtually all fields of veterinary medicine. Our objective was to study the occurrence, phylogenetic relationships and antimicrobial resistance properties of MRSA isolated from ocular surfaces of horses prior to invasive procedures. Within a 49-week sampling period, ocular swabs obtained from 46 eyes of 44 horses, including eyes with clinical signs of conjunctivitis/blepharitis, keratitis or uveitis were screened for the presence of S...
August 2018: Veterinary Microbiology
Ying Han, Jing Wang, Zelong Zhao, Jingwen Chen, Hong Lu, Guangfei Liu
Mariculture sediment has been recognized as a major contributor of environmental antibiotic resistance genes (ARGs), which are challenging the treatment of infections worldwide. Both antibiotics and fishmeal are used in aquaculture, and each has the potential to facilitate ARG dissemination, however their combined impact on the sediment resistome and their relative contribution remain unclear. In this study, microcosms were exposed to varying concentrations of tetracycline with or without fishmeal (0.1% wt/wt) for 14 days...
July 30, 2018: Environmental Pollution
Rishikesh Satish Parulekar, Kailas Dashrath Sonawane
Because of the lack of structural studies on aminoglycoside phosphotransferase (APH) from prevalent volatile human pathogen Bacillus cereus, aminoglycoside resistance therapeutics research remains elusive. Hence, in this computational study, we have performed homology modeling, molecular docking, molecular dynamics (MD), and principal component analysis studies on APH from B. cereus. The structure of APH was predicted by homology modeling using MODELLER 9v12 and validated for its stereochemical qualities. Sequence analysis study of the template (Protein Data Bank ID: 3TDW) and APH from B...
August 3, 2018: Journal of Cellular Biochemistry
Kelly M Craft, Jennifer A Gaddy, Steven D Townsend
Human milk oligosaccharides (HMOs) possess antimicrobial and antibiofilm activity against Group B Streptococcus (GBS). HMOs were screened for their ability to potentiate antibiotic activity. We observed that HMOs potentiate the function of aminoglycosides, lincosamides, macrolides, and tetracyclines on a strain specific basis but not β-lactams or glycopeptides that inhibit cell wall synthesis. These findings are notable as GBS has evolved high levels of resistance toward aminoglycosides, macrolides, and tetracyclines...
August 6, 2018: ACS Chemical Biology
Julia G Conner, Jackie Smith, Erdal Erol, Stephan Locke, Erica Phillips, Craig N Carter, Agricola Odoi
BACKGROUND: Resistance to commonly used antimicrobials is a growing concern in both human and veterinary medicine. Understanding the temporal changes in the burden of the problem and identifying its determinants is important for guiding control efforts. Therefore, the objective of this study was to investigate temporal patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) between 1993 and 2009...
2018: PloS One
H Chen, K M Au, K E Hsu, C K Lai, J Myint, Y F Mak, S Y Lee, T Y Wong, N C Tsang
INTRODUCTION: A point prevalence survey was conducted to study the epidemiology of and risk factors associated with multidrug-resistant organism carriage among residents in residential care homes for the elderly (RCHEs). METHODS: A total of 20 RCHEs in Hong Kong were selected by stratified single-stage cluster sampling. All consenting residents aged ≥65 years from the selected RCHEs were surveyed by collection of nasal swab, axillary swab, rectal swab or stool on one single day for each home...
July 30, 2018: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
Julia Ernst, Mareike Klinger-Strobel, Kathrin Arnold, Jana Thamm, Anita Hartung, Mathias W Pletz, Oliwia Makarewicz, Dagmar Fischer
Pulmonary infections with Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) are difficult to treat and related with high mortality in some diseases like cystic fibrosis due to the recurrent formation of biofilms. The biofilm formation hinders efficient treatment with inhaled antibiotics due to a low penetration of the antibiotics through the polyanionic biofilm matrix and increased antimicrobial resistance of the biofilm-embedded bacteria. In this study, tobramycin (Tb) was encapsulated in particles based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-co-poly(D,L-lactide-co-glycolide) diblock (PEG-PLGA) to overcome the biofilm barrier with particle sizes of 225-231 nm (nanoparticles) and 896-902 nm (microparticles), spherical shape and negative zeta potentials...
July 28, 2018: European Journal of Pharmaceutics and Biopharmaceutics
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