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Gram-negative resistance

Troy A Skwor, Stephanie Klemm, Hanyu Zhang, Brianna Schardt, Stephanie Blaszczyk, Matthew A Bork
Increasing rates of antibiotic resistance coupled with the lack of novel antibiotics threatens proper clinical treatment and jeopardizes their use in prevention. A photodynamic approach appears to be an innovative treatment option, even for multi-drug resistant strains of bacteria. Three components are utilized in photodynamic inactivation: a photosensitizer, light source, and oxygen. Variations in photosensitizers strongly influence microbial binding and bactericidal activity. In this study, four different cationic metalloporphyrins (Cu(2+), Fe(2+), Pd(2+), Zn(2+)) were compared to the free-base ligand 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin regarding their electronic properties and generation of reactive oxygen species upon subsequent 405nm violet-blue irradiation...
October 15, 2016: Journal of Photochemistry and Photobiology. B, Biology
Narges Abdali, Jerry Matthew Parks, Keith Haynes, Julie L Chaney, Adam T Green, David Wolloscheck, John K Walker, Valentin V Rybenkov, Jerome Yves Baudry, Jeremy C Smith, Helen I Zgurskaya
Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for development of effective EPIs, especially in light of constantly emerging resistance. Here, we describe EPIs that interact with periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel...
October 21, 2016: ACS Infectious Diseases
Marta Gibert, Sonia Paytubi, Sergi Beltrán, Antonio Juárez, Carlos Balsalobre, Cristina Madrid
Plasmids of the incompatibility group HI1 (IncHI1) have been isolated from several Gram-negative pathogens and are associated with the spread of multidrug resistance. Their conjugation is tightly regulated and it is inhibited at temperatures higher than 30°C, indicating that conjugation occurs outside warm-blooded hosts. Using R27, the prototype of IncHI1 plasmids, we report that plasmid transfer efficiency in E. coli strongly depends on the physiological state of the donor cells. Conjugation frequency is high when cells are actively growing, dropping sharply when cells enter the stationary phase of growth...
October 21, 2016: Environmental Microbiology
Matteo Bassetti, Alessia Carnelutti, Maddalena Peghin
The isolation of multi-drug-resistant gram-negative (MDRGN) pathogens has progressively increased worldwide and has been associated with important delays in the prescription of an adequate antibiotic treatment, resulting in increased mortality rates. Patient's stratification for MDRGN infections to optimize the prescription of an adequate empiric antimicrobial regimen is crucial. Areas covered: This article covers MDRGN epidemiology, with a specific focus on risk factors for harbouring infections sustained by extended-spectrum-Beta-lactamase (ESBL), carbapenem resistant Enterobacteriacae (CRE), MDR Pseudomonas aeruginosa and MDR Acinetobacter baumanii...
October 21, 2016: Expert Review of Anti-infective Therapy
Lesley J Scott
Intravenous ceftaroline fosamil (Zinforo™), a prodrug that is rapidly converted to its active metabolite ceftaroline, is approved for use in adults and children (from 2 months of age) with complicated skin and soft tissue infections (cSSTIs) or community-acquired pneumonia (CAP). In several multinational trials, ceftaroline fosamil was an effective and generally well tolerated treatment in adult and paediatric patients with cSSTIs or CAP. In the phase 3 CANVAS trials, ceftaroline fosamil treatment was noninferior to vancomycin plus aztreonam in adults with cSSTIs...
October 20, 2016: Drugs
R Fussen, S Lemmen
Multidrug resistant (MDR) bacteria present an increasing threat for intensive care patients. Whereas colonization of intensive care patients with methicillin-resistant staphylococcus aureus (MRSA) in German ICUs has remained at a constant level in recent years and therapeutic options have improved, colonization and infections with MDR gram-negative bacteria and vancomycin-resistant enterococci are increasing year by year. Only a few or even no therapeutic options remain for the treatment of these bacteria...
October 20, 2016: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Barbara Maciejewska, Bartosz Roszniowski, Akbar Espaillat, Agata Kęsik-Szeloch, Grazyna Majkowska-Skrobek, Andrew M Kropinski, Yves Briers, Felipe Cava, Rob Lavigne, Zuzanna Drulis-Kawa
Lytic bacteriophages and phage-encoded endolysins (peptidoglycan hydrolases) provide a source for the development of novel antimicrobial strategies. In the present study, we focus on the closely related (96 % DNA sequence identity) environmental myoviruses vB_KpnM_KP15 (KP15) and vB_KpnM_KP27 (KP27) infecting multidrug-resistant Klebsiella pneumoniae and Klebsiella oxytoca strains. Their genome organisation and evolutionary relationship are compared to Enterobacter phage phiEap-3 and Klebsiella phages Matisse and Miro...
October 21, 2016: Applied Microbiology and Biotechnology
Katherine C Faulkner, Katherine A Hurley, Douglas B Weibel
Antibiotic adjuvant therapy represents an exciting opportunity to enhance the activity of clinical antibiotics by co-dosing with a secondary small molecule. Successful adjuvants decrease the concentration of antibiotics used to defeat bacteria, increase activity (in some cases introducing activity against organisms that are drug resistant), and reduce the frequency at which drug-resistant bacteria emerge. We report that 5-alkyloxytryptamines are a new class of broad-spectrum antibacterial agents with exciting activity as antibiotic adjuvants...
October 5, 2016: Bioorganic & Medicinal Chemistry Letters
Weiwei Wang, Ting Jiang, Weihong Zhang, Chunyu Li, Jun Chen, Dandan Xiang, Kejiang Cao, Lian-Wen Qi, Ping Li, Wei Zhu, Wensen Chen, Yan Chen
The study was undertaken to describe the profile of patients and the characteristics of all multidrug-resistant gram-negative bacteria (MDR-GNB) and to assess mortality. We examined 138 patients with bloodstream infections (BSIs) caused by MDR-GNB. Clinical characteristics, antibiotic therapy, and in-hospital mortality were analyzed. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. The in-hospital mortality rate was 25.4%. Univariate analysis revealed that comorbidities and inadequate initial antimicrobial treatment could increase risk of death...
October 17, 2016: American Journal of Infection Control
Brendan W Corey, Mitchell G Thompson, Lauren E Hittle, Anna C Jacobs, Edward A Asafo-Adjei, William Huggins, Roberta J Melander, Christian Melander, Robert K Ernst, Daniel V Zurawski
Acinetobacter baumannii are gram-negative bacilli that pose a constant threat to susceptible patients because of increased resistance to multiple antibiotics and persistence in the hospital environment. After genome analysis, we discovered that A. baumannii harbor genes that share homology to an enzymatic pathway that elongates long chain fatty acids (LCFA) in fungi. Previously, 1,2,4-Triazolidine-3-thiones (T-3-Ts) were shown to inhibit hyphae production in fungi, and this same LCFA elongation pathway was implicated as the possible target...
October 20, 2016: ACS Infectious Diseases
Sandrine Alibert, Joannah N'Gompazza Diarra, Jessica Hernandez, Aurélien Stutzmann, Marwa Fouad, Gérard Boyer, Jean-Marie Pagès
Worrying levels of bacterial resistance have been reported worldwide involving the failure of many available antibiotic treatments. Multidrug resistance (MDR) in Gram-negative bacteria is often ascribed to the presence of multiple and different resistance mechanisms in the same strain. RND efflux pumps play a major role and are an attractive target to discover new antibacterial drugs. Areas covered: This review discusses the prevalence of efflux pumps, their overexpression in clinical scenarios, their polyselectivity, their effect on the intracellular concentrations of various antibiotics associated with the alteration of the membrane permeability and their involvement in pathogenicity are discussed...
October 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
Li Fang, Qiong Chen, Keren Shi, Xi Li, Qiucheng Shi, Fang He, Jiancang Zhou, Yunsong Yu, Xiaoting Hua
Klebsiella pneumoniae is a gram-negative bacterium that causes numerous diseases, including pneumonia and urinary tract infections. An increase in multidrug resistance has complicated the treatment of these bacterial infections, and although tigecycline shows activity against a broad spectrum of bacteria, resistant strains have emerged. In this study, the whole genomes of two clinical and six laboratory-evolved strains were sequenced to identify putative mutations related to tigecycline resistance. Of seven tigecycline-resistant strains, seven (100%) had ramR mutations, five (71...
2016: PloS One
Ayse Ruveyda Ugur, Hatice Turk Dagi, Bahadir Ozturk, Gulsum Tekin, Duygu Findik
BACKGROUND: Methicillin resistance is a serious health concern since it has spread among Staphylococcus aureus and coagulase-negative Staphylococci (CoNS) that are frequent community and nosocomial pathogens worldwide. Methicillin-resistant strains are often resistant to other classes of antibiotics, making their treatment difficult. Nigella sativa oil is known to be active against Gram-positive cocci, yet its in vitro cytotoxicity is rarely investigated, is a proper and powerful candidate for treatment of methicillin-resistant isolates...
July 2016: Pharmacognosy Magazine
Athanasios Tselebonis, Evangelia Nena, Christos Nikolaidis, Theocharis Konstantinidis, Christos Kontogiorgis, Maria Panopoulou, Theodore C Constantinidis
OBJECTIVE: To monitor microbes, focusing on drug resistance, on the hands of the personnel of four departments of a tertiary hospital (ICU, neonatal unit, internal medicine ward and surgical ward) and explore differences between departments, professions and genders. MATERIALS AND METHODS: Hand sampling from 125 healthcare employees was conducted followed by isolation, identification and antibiotic resistance profiling of different microbial species. RESULTS: Staphylococcus spp was the most prevalent microbe (76/125, 60...
September 1, 2016: Folia Medica
Peng Sang, Yan Shi, Peng Teng, Annie Cao, Hai Xu, Qi Li, Jianfeng Cai
Antibiotic resistance is one of the biggest public concerns in the 21st century. Host-defense peptides (HDPs) can potentially mitigate the problem through the disruption of bacterial membranes; however, they suffer from moderate activity and low stability. We recently developed a new class of peptidomimetics termed "AApeptides". This class of peptidomimetics can mimic the mechanism of action of HDPs, and effectively arrest the growth of multidrug resistant Gram-positive and Gram-negative bacteria. As they are built on unnatural backbone, they are highly resistant to proteolytic degradation...
October 18, 2016: Current Topics in Medicinal Chemistry
Sara A Buckman, Tamara Krekel, Anouk E Muller, John E Mazuski
The treatment of complicated intra-abdominal infections (cIAI) is increasingly challenging due to increased resistance of Gram-negative organisms. These multidrug resistant organisms lead to an increase in morbidity and mortality. This has led to renewed interest in use of older β-lactam antibiotics in combination with newer β-lactamase inhibitors. Ceftazidime-avibactam is one of the newest such combination antibiotics, which has been released for treatment of complicated intra-abdominal infections in combination with metronidazole...
October 19, 2016: Expert Opinion on Pharmacotherapy
Ia Kusradze, Natia Karumidze, Sophio Rigvava, Teona Dvalidze, Malkhaz Katsitadze, Irakli Amiranashvili, Marina Goderdzishvili
Acinetobacter baumannii is a gram-negative, non-motile bacterium that, due to its multidrug resistance, has become a major nosocomial pathogen. The increasing number of multidrug resistant (MDR) strains has renewed interest in phage therapy. The aim of our study was to assess the effectiveness of phage administration in Acinetobacter baumannii wound infections in an animal model to demonstrate phage therapy as non-toxic, safe and alternative antibacterial remedy. Using classical methods for the study of bacteriophage properties, we characterized phage vB-GEC_Ab-M-G7 as a dsDNA myovirus with a 90 kb genome size...
2016: Frontiers in Microbiology
Ai-Jun Pan, Qing Mei, Ying Ye, Hong-Ru Li, Bao Liu, Jia-Bin Li
The purpose of this study was to validate the mutant selection window (MSW) hypothesis in vitro and in vivo with Escherichia coli and Pseudomonas aeruginosa exposed to fosfomycin. Two standard strains of Gram-negative bacteria, those are E. coli ATCC 25922 and P. aeruginosa ATCC 27853, were exposed to fosfomycin at concentrations below MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC in Luria-Bertani broth and in a tissue-cage infection model, respectively. With the in vitro time-kill studies, there were bacterial re-growth and emergence of resistance thereafter for both strains at antibiotic concentrations of × 4, × 8 and × 16 MIC...
October 19, 2016: Journal of Antibiotics
Darja Kušar, Karin Šrimpf, Petra Isaković, Lina Kalšek, Javid Hosseini, Irena Zdovc, Tina Kotnik, Modest Vengušt, Gabrijela Tavčar-Kalcher
BACKGROUND: Bacterial intercellular communication, called quorum sensing, takes place via the production and collective response to signal molecules. In Gram-negative bacteria, like Pseudomonas aeruginosa, these signaling molecules are N-acylhomoserine lactones (AHLs). P. aeruginosa is a common cause of inflammation of the ear canal (otitis externa) in dogs. It employs quorum sensing to coordinate the expression of host tissue-damaging factors, which are largely responsible for its virulence...
October 18, 2016: BMC Veterinary Research
Dar-Chone Chow, Kacie Rice, Wanzhi Huang, Robert L Atmar, Timothy G Palzkill
The β-lactamase inhibitory protein (BLIP) binds and inhibits a wide range of class A β-lactamases including the TEM-1 β-lactamase (Ki= 0.5 nM), which is widely present in Gram-negative bacteria, and the KPC-2 β-lactamase (Ki= 1.2 nM), which hydrolyzes virtually all clinically useful β-lactam antibiotics. The extent to which the specificity of a protein that binds a broad range of targets can be modified to display narrow specificity was explored in this study by engineering BLIP to bind selectively to KPC-2 β-lactamase...
October 18, 2016: ACS Infectious Diseases
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