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Gram negative resistance

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
P Ioannou, M Stavroulaki, V Mavrikaki, I Papakitsou, S Panagiotakis
WHAT IS KNOWN AND OBJECTIVE: Hyponatremia is the most common electrolyte disorder. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the main cause of euvolemic hyponatremia and is often associated with medications or underlying diseases. Linezolid is a potent antibiotic against resistant Gram-positive microorganisms that has been associated with mild hyponatremia, yet with a mechanism different from SIADH. CASE SUMMARY: We present the case of a patient who developed severe hyponatremia during treatment with linezolid for an ampicillin-resistant E...
March 14, 2018: Journal of Clinical Pharmacy and Therapeutics
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
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
I-Ling Chen, Chen-Hsiang Lee, Shih-Wen Ting, Lily Yu-Chin Wang
Objectives: The increasing number of reports on infections due to carbapenem-resistant Gram-negative bacilli (GNB) has raised concerns, because they have complicated empiric or guided antibiotic therapy for critically ill patients. We aimed to develop a scoring system to predict nosocomial imipenem-resistant GNB (IR-GNB) septicemia among the critically ill patients. Materials and methods: The study included critically ill adult patients with nosocomial GNB septicemia at Kaohsiung Chang Gung Memorial Hospital (CGMH) in 2013-2015, and the scoring system for predicting IR-GNB septicemia was developed, followed by prospective validation conducted among patients at Linkou CGMH and Kaohsiung CGMH between January and June, 2016...
2018: Infection and Drug Resistance
Alasdair T M Hubbard, Sian Davies, Laura Baxter, Sarah Thompson, Mark Collery, Daniel Hand, Daniel John Thomas, Colin Fink
Comparison of the genome of the Gram negative human pathogen Haemophilus quentini MP1 with other Haemophilus species revealed that, although it is more closely related to Haemophilus haemolyticus than Haemophilus influenzae, the pathogen is in fact genetically distinct, a finding confirmed by phylogenetic analysis using the H. influenzae multilocus sequence typing genes. Further comparison with two other H. quentini strains recently identified in Canada revealed that these three genomes are more closely related than any other Haemophilus species, however there is still some sequence variation...
March 13, 2018: Genome Génome / Conseil National de Recherches Canada
R Cantón, E Loza, J Aznar, R Barrón-Adúriz, J Calvo, F J Castillo, E Cercenado, R Cisterna, F González-Romo, J L López-Hontangas, A I Suárez-Barrenechea, F Tubau, B Molloy, D López-Mendoza
OBJECTIVE: The SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study monitors antimicrobial susceptibility and extended spectrum β-lactamases (ESBLs) in Gram-negative bacilli recovered from intra-abdominal infections (IAI). METHODS: Antimicrobial susceptibility of 5,343 isolates from IAI recovered in 11 centres during the 2011-2015 SMART-Spain program was analysed by standard microdilution (EUCAST criteria) and compared with that from 2002-2010...
March 12, 2018: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
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
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
Melissa D Barnes, Christopher R Bethel, Jim Alsop, Scott A Becka, Joseph D Rutter, Krisztina M Papp-Wallace, Robert A Bonomo
Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen acquired predominantly by immunosuppressed patients during hospitalization. Relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates the Pseudomona s-Derived Cephalosporinase (PDC-3) with a k 2 / K of 41,400 M-1 s-1 and a k off of 0.00095 s-1 Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant (MDR) P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Aliana Meneses Ferreira, Frederico Moreira, Thais Guimaraes, Fernanda Spadão, Jessica Fernandes Ramos, Marjorie Vieira Batista, Jayr Schmidt Filho, Silvia Figueiredo Costa, Vanderson Rocha
BACKGROUND: Bloodstream infections (BSI) are a major complication in the early phase of a hematopoietic stem cell transplant (HSCT). AIM: To describe the incidence and risk factors for BSI occurring in the pre-engraftment phase of HSCT and its impact on mortality. METHODS: We retrospectively analysed clinical variables of 232 HSCT patients between 2014 and 2015. Univariate Cox regression analyses were performed to test the association between each covariate and the outcome...
March 9, 2018: Journal of Hospital Infection
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
Timothy Palzkill
The most common mechanism of resistance to β-lactam antibiotics in Gram-negative bacteria is the production of β-lactamases that hydrolyze the drugs. Class A β-lactamases are serine active-site hydrolases that include the common TEM, CTX-M, and KPC enzymes. The TEM enzymes readily hydrolyze penicillins and older cephalosporins. Oxyimino-cephalosporins, such as cefotaxime and ceftazidime, however, are poor substrates for TEM-1 and were introduced, in part, to circumvent β-lactamase-mediated resistance. Nevertheless, the use of these antibiotics has lead to evolution of numerous variants of TEM with mutations that significantly increase the hydrolysis of the newer cephalosporins...
2018: Frontiers in Molecular Biosciences
Annie W T Lee, Johnson K S Lam, Ricky K W Lam, Wan H Ng, Ella N L Lee, Vicky T Y Lee, Po P Sze, Rahim Rajwani, Kitty S C Fung, Wing K To, Rodney A Lee, Dominic N C Tsang, Gilman K H Siu
Objective: This study evaluated the capability of a MALDI Biotyper system equipped with the newly introduced MBT STAR-BL module to simultaneously perform species identification and β-lactamase-mediated resistance detection in bacteremia -causing bacteria isolated from cultured isolates and patient-derived blood cultures (BCs). Methods: Two hundred retrospective cultured isolates and 153 prospective BCs containing Gram-negative rods (GNR) were collected and subjected to direct bacterial identification, followed by the measurement of β-lactamase activities against ampicillin, piperacillin, cefotaxime, ceftazidime, and meropenem using the MBT STAR-BL module...
2018: Frontiers in Microbiology
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
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
Jian Sun, Huimin Zhang, Ya-Hong Liu, Youjun Feng
Antibiotic resistance has become a global public health priority. Polymyxins, a family of cationic polypeptide antibiotics, act as a final line of refuge against severe infections by Gram-negative pathogens with pan-drug resistance. Unfortunately, this last-resort antibiotic has been challenged by the emergence and global spread of mobilized colistin resistance determinants (mcr). Given the fact that it has triggered extensive concerns worldwide, we present here an updated view of MCR-like colistin resistance...
March 7, 2018: Trends in Microbiology
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