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Multidrug resistant gram negative bacteria

A Gramegna, B C Millar, F Blasi, J S Elborn, D G Downey, J E Moore
INTRODUCTION: Pulmonary exacerbations in people with Cystic Fibrosis (CF), with chronic Gram-negative pathogens, are associated with reduced survival. These pathogens are usually treated with repeated courses of systemic antibiotics. However there is a linked emergence of multidrug resistant (MDR) pathogens. Ceftolozane/tazobactam is a new cephalosporin/beta-lactamase inhibitor combination that has been demonstrated to have good activity against MDR Pseudomonas aeruginosa. MATERIAL & METHODS: In this study ceftolozane/tazobactam was compared to other commonly used intravenous antibiotics against 193 non-fermenting Gram-negative bacteria isolated from CF sputum specimens, including P...
March 17, 2018: Journal of Global Antimicrobial Resistance
B Yun, T Zhang, M A K Azad, J Wang, C J Nowell, P Kalitsis, T Velkov, D F Hudson, J Li
Increasing incidence of multidrug-resistant bacteria presents an imminent risk to global health. Polymyxins are 'last-resort' antibiotics against Gram-negative 'superbugs'; however, nephrotoxicity remains a key impediment in their clinical use. Molecular mechanisms underlying this nephrotoxicity remain poorly defined. Here, we examined the pathways which led to polymyxin B induced cell death in vitro and in vivo. Human proximal tubular cells were treated with polymyxin B (12.5-100 μM) for up to 24 h and showed a significant increase in micronuclei frequency, as well as abnormal mitotic events (over 40% in treated cells, p < 0...
March 20, 2018: Archives of Toxicology
Vincent Lôme, Jean-Michel Brunel, Jean-Marie Pagès, Jean-Michel Bolla
Antibiotic resistance is now a worldwide therapeutic problem. Since the beginning of anti-infectious treatment bacteria have rapidly shown an incredible ability to develop and transfer resistance mechanisms. In the last decades, the design variation of pioneer bioactive molecules has strongly improved their activity and the pharmaceutical companies partly won the race against the clock. Since the 1980s, the new classes of antibiotics that emerged were mainly directed to Gram-positive bacteria. Thus, we are now facing to multidrug-resistant Gram-negative bacteria, with no therapeutic options to deal with them...
2018: Frontiers in Microbiology
Alessandro Russo, Simone Giuliano, Giancarlo Ceccarelli, Francesco Alessandri, Alessandra Giordano, Grazia Brunetti, Mario Venditti
Objectives: a significant cause of mortality in intensive care unit (ICU) is represented by multidrug-resistant (MDR) gram-negative bacteria, such as MDR Acinetobacter baumannii (MDR-AB) and Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). Aim of the present study was the comparison of clinical features, therapy and outcome of patients who developed septic shock due to either MDR-AB or KPC-Kp. Methods: were retrospectively analyzed patients admitted to the intensive care unit (ICU) of a teaching hospital, from November 2010 to December 2015, who developed septic shock due to MDR-AB or KPC-Kp infection...
March 19, 2018: Antimicrobial Agents and Chemotherapy
Bing Hu, Yang Shen, Jozef Adamcik, Peter Fischer, Mirjam Schneider, Martin J Loessner, Raffaele Mezzenga
Adaptable hydrogel networks with reversible connectivity have emerged as a promising platform for biomedical applications. Synthetic copolymers and Low-Molecular Weight Gelators (LMWG) have been shown to form reversible hydrogels through self-assembly of the molecules driven by self complementary hydrophobic interaction and hydrogen bonding. Here, inspired by the adhesive proteins secreted by mussels, we found that simply adding natural polyphenols, such as epigallocatechin gallate (EGCG) to amyloid fibrils present in the nematic phase, successfully drives the formation of hydrogels through self-assembly of the hybrid supramolecules...
March 19, 2018: ACS Nano
Bich-Tram Huynh, Elsa Kermorvant-Duchemin, Perlinot Herindrainy, Michael Padget, Feno Manitra Jacob Rakotoarimanana, Herisoa Feno, Elisoa Hariniaina-Ratsima, Tanjona Raheliarivao, Awa Ndir, Sophie Goyet, Patrice Piola, Frederique Randrianirina, Benoit Garin, Jean-Marc Collard, Didier Guillemot, Elisabeth Delarocque-Astagneau
Severe bacterial infections are a leading cause of death among neonates in low-income countries, which harbor several factors leading to emergence and spread of multidrug-resistant bacteria. Low-income countries should prioritize interventions to decrease neonatal infections; however, data are scarce, specifically from the community. To assess incidence, etiologies, and antimicrobial drug-resistance patterns of neonatal infections, during 2012-2014, we conducted a community-based prospective investigation of 981 newborns in rural and urban areas of Madagascar...
April 2018: Emerging Infectious Diseases
Sandra C Vega, Diana A Martínez, María Del S Chalá, Hernán A Vargas, Jaiver E Rosas
Multidrug resistance of pathogenic bacteria has become a public health crisis that requires the urgent design of new antibacterial drugs such as antimicrobial peptides (AMPs). Seeking to obtain new, lactoferricin B (LfcinB)-based synthetic peptides as viable early-stage candidates for future development as AMPs against clinically relevant bacteria, we designed, synthesized and screened three new cationic peptides derived from bovine LfcinB. These peptides contain at least one RRWQWR motif and differ by the copy number (monomeric, dimeric or tetrameric) and structure (linear or branched) of this motif...
2018: Frontiers in Microbiology
Norelle Sherry, Benjamin Howden
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the "re-discovery" of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas Covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam...
March 15, 2018: Expert Review of Anti-infective Therapy
Dehbia Benkerrou, Matteo Ceccarelli
One of the greatest health threats facing modern medicine is the emergence of new bacterial strains which are increasingly resistant to almost all currently available antibiotics. According to a CDC (Center for Disease Control and Prevention) report published in 2013, 63% of Acinetobacter species have been identified as Multidrug resistant strains. As for other Gram-negative bacteria, the presence of an outer membrane increases the intrinsic resistance of A. baumannii to most antibiotics. The outer membrane of A...
March 15, 2018: Physical Chemistry Chemical Physics: PCCP
Nicholas Agyepong, Usha Govinden, Alex Owusu-Ofori, Sabiha Yusuf Essack
Background: Multidrug-resistant Gram-negative bacteria have emerged as major clinical and therapeutic dilemma in hospitals in Ghana.To describe the prevalence and profile of infections attributable to multidrug-resistant Gram-negative bacteria among patients at the Komfo Anokye Teaching Hospital in the Ashanti region of Ghana. Methods: Bacterial cultures were randomly selected from the microbiology laboratory from February to August, 2015. Bacterial identification and minimum inhibitory concentrations were conducted using standard microbiological techniques and the Vitek-2 automated system...
2018: Antimicrobial Resistance and Infection Control
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
Hannah Y P Phoon, Hazilawati Hussin, Baizurah Mohd Hussain, Shu Yong Lim, Jia Jie Woon, Yi Xian Er, Kwai Lin Thong
OBJECTIVES: Hospital environments are potential reservoirs of bacteria associated with nosocomial infections. Here, we determined the distribution of cultivable environmental bacteria of clinical importance from a Malaysian tertiary hospital and to investigate their resistotypes and genotypes. METHODS: Swab and fluid samples (n=358) from healthcare workers' hands, frequently touched surfaces, medical equipment, patients' immediate surroundings, ward sinks and toilets and solutions or fluids of 12 selected wards were collected...
March 11, 2018: Journal of Global Antimicrobial Resistance
Brice Felden, Vincent Cattoir
The extensive use of antibiotics has resulted in a situation where multidrug-resistant pathogens have become a severe menace to human health worldwide. A deeper understanding of the principles used by pathogens to adapt, respond and resist against antibiotics will pave the road to drugs with novel mechanisms. For bacteria, antibiotics are clinically-relevant stresses that induce protective responses. The recent implication of regulatory RNAs (sRNAs) into antibiotic response and resistance in many bacterial pathogens suggests that they should be considered as innovative drug targets...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Silvano Esposito, Silvana Noviello, Francesco De Caro, Giovanni Boccia
Skin and soft tissue infections (SSTIs) involve a heterogeneous group of entities with different clinical presentations classified according to several specific criteria. Because of their great variability, their incidence and prevalence is difficult to accurately determine. Yet it is generally thought that the rate of SSTIs is globally increasing due to an aging population, strictly associated with the increase in the number of critical and immunocompromised patients. The aetiology of SSTIs is also extremely variable, reflecting the noteworthy heterogeneity of their clinical presentations and their epidemiology...
March 1, 2018: Le Infezioni in Medicina
Ardeshir Rineh, John B Bremner, Michael R Hamblin, Anthony R Ball, George P Tegos, Michael J Kelso
Resistance of bacteria to antibiotics is a public health concern worldwide due to the increasing failure of standard antibiotic therapies. Antimicrobial photodynamic inactivation (aPDI) is a promising non-antibiotic alternative for treating localized bacterial infections that uses non-toxic photosensitizers and harmless visible light to produce reactive oxygen species and kill microbes. Phenothiazinium photosensitizers like methylene blue (MB) and toluidine blue O are hydrophobic cations that are naturally expelled from bacterial cells by multidrug efflux pumps, which reduces their effectiveness...
February 24, 2018: Bioorganic & Medicinal Chemistry Letters
Konrad Gwozdzinski, Saina Azarderakhsh, Can Imirzalioglu, Linda Falgenhauer, Trinad Chakraborty
The plasmid-located colistin resistance gene ( mcr - 1 ) confers low-level resistance to colistin, a last-line antibiotic against multidrug-resistant Gram-negative bacteria. Current EUCAST/CLSI recommendations require the use of a broth microdilution (BMD) method in cation-adjusted Mueller-Hinton (CA-MH) for colistin susceptibility testing, but approximately 15% of all MCR-1-producers classify as sensitive in this medium. Here we report on an improved calcium-enhanced Mueller-Hinton (CE-MH) medium that permits simple and reliable determination of mcr-1 -producing Enterobacteriaceae Colistin susceptibility for 50 mcr-1 -encoding isolates of E...
March 7, 2018: Journal of Clinical Microbiology
Peter M Hawkey, Roderic E Warren, David M Livermore, Cliodna A M McNulty, David A Enoch, Jonathan A Otter, A Peter R Wilson
The Working Party makes more than 100 tabulated recommendations in antimicrobial prescribing for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB) and suggest further research, and algorithms for hospital and community antimicrobial usage in urinary infection. The international definition of MDR is complex, unsatisfactory and hinders the setting and monitoring of improvement programmes. We give a new definition of multiresistance. The background information on the mechanisms, global spread and UK prevalence of antibiotic prescribing and resistance has been systematically reviewed...
March 1, 2018: Journal of Antimicrobial Chemotherapy
Yong Zhang, Eva Zborníková, Dominik Rejman, Kenn Gerdes
The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identified in Escherichia coli We applied DRaCALA (<u>d</u>ifferential<u>ra</u>dial<u>c</u>apillary<u>a</u>ction of<u>l</u>igand<u>a</u>ssay) to identify (p)ppGpp-protein interactions...
March 6, 2018: MBio
Yue Li, Liqiang Liu, Shanshan Song, Hua Kuang, Chuanlai Xu
Increasing attention is now being directed to the utilization of polymyxin B (PMB) as a last-line treatment for life-threatening infections caused by multidrug resistant Gram-negative bacteria. Unfortunately, polymyxins resistance is also increasingly reported, leaving a serious threat to human health. Therefore, the establishment of rapid detection methods for PMB residues is highly essential to ensure public health. In this study, two monoclonal antibodies (mAb; 2A2 and 3C6) were obtained using PMB-bovine serum albumin as the immunogen and PMB-ovalbumin as the coating antigen, which were prepared with N -(γ-maleimidobutyryloxy) succinimide ester and glutaraldehyde as cross-linking agents, respectively...
March 5, 2018: Nanomaterials
Jin Wu, Fred Racine, Michael K Wismer, Katherine Young, Donna M Carr, Jing C Xiao, Ravi Katwaru, Qian Si, Paul Harradine, Mary Motyl, Pratik R Bhagunde, Matthew L Rizk
Resistance to antibiotics among bacterial pathogens is rapidly spreading and therapeutic options against multidrug-resistant bacteria are limited. There is an urgent need for new drugs, especially those that can circumvent the broad array of resistance pathways that bacteria have evolved. In this study, we assessed the pharmacokinetic/pharmacodynamic relationship of the novel β-lactamase inhibitor relebactam (MK-7655; REL) in a hollow fiber infection model. REL is intended for use with the carbapenem β-lactam antibiotic imipenem for the treatment of Gram-negative bacterial infections...
March 5, 2018: Antimicrobial Agents and Chemotherapy
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