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beta-lactamase inhibitor

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https://www.readbyqxmd.com/read/29038260/meropenem-vaborbactam-resistance-selection-prevention-and-molecular-mechanisms-in-mutants-of-kpc-producing-klebsiella-pneumoniae
#1
Dongxu Sun, Debora Rubio-Aparicio, Kirk Nelson, Michael N Dudley, Olga Lomovskaya
Vaborbactam (formerly RPX7009) is a new beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Klebsiella pneumoniaecarbapenemases (KPC). It has been developed in combination with meropenem. The objective of these studies was to identify concentrations of both agents associated with selecting or preventing single-step mutations leading to reduced sensitivity to the combination, and to characterize the selected mutations. Eighteen strains of KPC-producing Klebsiella pneumoniae with varying degrees of sensitivity to meropenem (MIC 8-512 μg/ml) and meropenem-vaborbactam (≤0...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29020364/antimicrobial-resistance-in-gram-negative-rods-causing-bacteremia-in-hematopoietic-stem-cell-transplant-patients-intercontinental-prospective-study-of-infectious-diseases-working-party-of-the-european-bone-marrow-transplantation-group
#2
Diana Averbuch, Gloria Tridello, Jennifer Hoek, Malgorzata Mikulska, Hamdi Akan, Lucrecia Yanez San Segundo, Thomas Pabst, Tülay Özçelik, Galina Klyasova, Irene Donnini, Depei Wu, Zafer Gülbas, Tsila Zuckerman, Aida Botelho de Sousa, Yves Beguin, Aliénor Xhaard, Emmanuel Bachy, Per Ljungman, Rafael de la Camara, Jelena Rascon, Isabel Ruiz Camps, Antonin Vitek, Francesca Patriarca, Laura Cudillo, Radovan Vrhovac, Peter J Shaw, Tom Wolfs, Tracey O'Brien, Batia Avni, Gerda Silling, Firas Al Sabty, Stelios Graphakos, Marja Sankelo, Henrik Sengeloev, Srinivas Pillai, Susanne Matthes, Frederiki Melanthiou, Simona Iacobelli, Jan Styczynski, Dan Engelhard, Simone Cesaro
Background: This intercontinental study aimed to study Gram-negative rods (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods: GNR bacteremias occurring during six months post-HSCT (February/2014-May/2015) were prospectively collected, and analysed for rates and risk factors for resistance to fluoroquinolones, non-carbapenem anti-Pseudomonas beta-lactams (non-carbapenems), carbapenems and multidrug-resistance (MDR). Results: Sixty-five HSCT centers from 25 countries (Europe, Australia, Asia) reported data on 655 GNR episodes/704 pathogens in 591 patients (Enterobacteriaceae, 73%; non-fermentatives, 24% and 3% others)...
July 26, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29017750/trends-and-relationship-between-antimicrobial-resistance-and-antibiotic-use-in-xinjiang-uyghur-autonomous-region-china-based-on-a-3-year-surveillance-data-2014-2016
#3
Haishaerjiang Wushouer, Zhao-Xia Zhang, Jian-Hua Wang, Ping Ji, Qing-Fang Zhu, Renagu Aishan, Lu-Wen Shi
PURPOSES: The objective of the study was to identify the trends and relations between antimicrobial resistance (AMR) and antibiotic use in the Xinjiang Uyghur Autonomous Region in Western China from 2014 to 2016. METHODS: A retrospective, descriptive analysis of AMR prevalence, and trends and relations between AMR and antibiotic use during the 3-year period was performed. RESULTS: Third-generation cephalosporin-resistant Escherichia coli was the most prevalent resistant pathogen in terms of both resistance density and resistance proportion...
October 7, 2017: Journal of Infection and Public Health
https://www.readbyqxmd.com/read/28942664/-clinical-aspects-of-severe-infections-caused-by-antibiotic-resistant-gram-negative-bacteria-the-empire-strikes-back
#4
János Sinkó
In our days, growing incidence of antibiotic resistant bacteria has become an eminent public health problem. For survival Gram-negative species possess several different tools to withstand antibiotics: they produce degrading and modifying enzymes, decrease their permeability or expel drug molecules. An increasing proportion of severe nosocomial infections are caused by strains resistant to several antimicrobials (multiresistant, extensively resistant or panresistant species). Development of new antibiotic compounds may serve as a possible solution to this problem...
October 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28929963/-comparison-of-phenotypic-methods-and-polymerase-chain-reaction-for-the-detection-of-carbapenemase-production-in-clinical-klebsiella-pneumoniae-isolates
#5
Yamaç Tekintaş, Feriha Çilli, Bayrı Eraç, Melike Yaşar, Sabire Şöhret Aydemir, Mine Hoşgör Limoncu
Being a member of the Enterobacteriaceae family, Klebsiella pneumoniae is an opportunistic pathogen that inhabits normal human microbiota and causes predominantly hospital-acquired infections. The emergence of K.pneumoniae isolates which are resistant particularly to the carbapenem group of antibiotics has led to an increase in hospitalization period, mortality and morbidity. Although different rates of resistance are observed between countries, regions and even healthcare facilities, there has been a rapid increase in the prevalence of carbapenem-resistant strains in the last 10 years...
July 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#6
REVIEW
H Wright, R A Bonomo, D L Paterson
BACKGROUND: Antibiotic resistance in Gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or have completed advanced clinical trials and that possess activity against resistant Gram-negative organisms...
October 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28859497/first-report-of-coexistence-of-ampc-beta-lactamase-genes-in-klebsiella-pneumoniae-strains-isolated-from-burn-patients
#7
Roya Ghanavati, Davood Darban-Sarokhalil, Fateme Navab-Moghadam, Hossein Kazemian, Gholamreza Irajian, Shabnam Razavi
Klebsiella spp. are among the most frequently isolated bacteria from burn wounds. These organisms are among the most important opportunistic pathogens, causing hospital-acquired and healthcare-associated infections worldwide. Limited information is available about prevalence of AmpC-producing Klebsiella pneumoniae from burn patients. Therefore, the aim of this study was to determine the characterization of AmpC beta-lactamase among K. pneumoniae isolated from burn patients. Samples were collected from wound specimens of patients with burn injury from a burn hospital in Tehran during 18 months (March 2015 to August 2016)...
September 1, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/28822333/virtual-screening-and-repositioning-of-inconclusive-molecules-of-beta-lactamase-bioassays-a-data-mining-approach
#8
Akshata Gad, Andrew Titus Manuel, Jinuraj K R, Lijo John, Sajeev R, Shanmuga Priya V G, Abdul Jaleel U C
This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules...
July 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28799307/guiding-principles-for-the-use-of-fluroquinolones-in-out-patient-community-settings-of-india-panel-consensus
#9
Agam Vora, K Krishnaprasad
INTRODUCTION: Respiratory tract infections have been an important cause of morbidity and mortality worldwide that is looming large especially in context of antibiotic resistance that is confronted both by a pulmonologist as well as a general practitioner. A reflection to this trend has been the rising phenomenon of MICs as shown the respiratory pathogens towards conventional antibiotics including macrolides or β lactam/β lactamase inhibitor combinations. Respiratory fluoroquinolones offer broad yet potent cover of respiratory pathogens leading to their obvious choice for empirical therapy for clinical persisters or high risk cases with prior history of antibiotics not-withstanding the clinical concerns in tropical countries...
August 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28697720/early-onset-pneumonia-after-liver-transplant-microbial-causes-risk-factors-and-outcomes-mansoura-university-egypt-experience
#10
Mohammad Khairy El-Badrawy, Raed El-Metwaly Ali, Amr Yassen, Mohammad Ahmad AbouElela, Rehab Ahmad Elmorsey
OBJECTIVES: Pneumonia has a negative effect on the outcome of liver transplant. Our aim was to analyze early-onset pneumonia that developed within the first month after transplant. MATERIALS AND METHODS: This prospective single-center study included 56 adult living-donor liver transplant recipients; those who developed early-onset pneumonia based on clinical and radiologic criteria were investigated as to causative pathogens and then followed up and compared with other recipients without pneumonia to illustrate risk factors, outcomes, and related mortality of posttransplant pneumonia...
October 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28634829/potential-inhibitory-effect-of-indolizine-derivatives-on-the-two-enzymes-nicotinamide-phosphoribosyltransferase-and-beta-lactamase-a-molecular-dynamics-study
#11
Beata Szefler, Przemysław Czeleń
Nicotinamide phosphoribosyl-transferases (NAMPT) are enzymes that play a role in targeting cancer metabolism, while beta lactamases are involved in bacterial resistance to beta-lactam antibiotics. Many protein inhibitors exhibit such property which is often correlated with their cellular potency. In order to understand such a phenomenon, the present article conducts an analysis of the dynamic behavior of complexes formed by the inhibitors, that is indolizine derivatives, with the studied enzymes. Both docking and molecular dynamics led to identification of their interactions and showed the mechanism of inhibition of the two studied enzymes...
July 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28631121/-prudent-use-of-antimicrobial-prophylaxis-prevention-of-increasing-antibiotic-resistance
#12
REVIEW
C Hein, A Pilatz, F M E Wagenlehner
BACKGROUND: The use of peri-operative antimicrobial prophylaxis during urological procedures to prevent postoperative complications is very common. OBJECTIVES: What kind of recommendations for reasonable use of peri-operative antimicrobial prophylaxis during urological procedures to prevent increasing antibiotic resistance and postoperative complications exist? METHODS: Review of evidence-based recommendations from literature and current Guidelines of the EAU...
June 19, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28574718/calibration-of-1-2-4-triazole-3-thione-an-original-zn-binding-group-of-metallo-%C3%AE-lactamase-inhibitors-validation-of-a-polarizable-mm-md-potential-by-quantum-chemistry
#13
Karolina Kwapien, Mirna Damergi, Serge Nader, Léa El Khoury, Zeina Hobaika, Richard G Maroun, Jean-Philip Piquemal, Laurent Gavara, Dorothée Berthomieu, Jean-François Hernandez, Nohad Gresh
In the context of the SIBFA polarizable molecular mechanics/dynamics (PMM/PMD) procedure, we report the calibration and a series of validation tests for the 1,2,4-triazole-3-thione (TZT) heterocycle. TZT acts as the chelating group of inhibitors of dizinc metallo-β-lactamases (MBL), an emerging class of Zn-dependent bacterial enzymes, which by cleaving the β-lactam bond of most β-lactam antibiotics are responsible for the acquired resistance of bacteria to these drugs. Such a study is indispensable prior to performing PMD simulations of complexes of TZT-based inhibitors with MBL's, on account of the anchoring role of TZT in the dizinc MBL recognition site...
June 22, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28483952/multicenter-study-of-outcomes-with-ceftazidime-avibactam-in-patients-with-carbapenem-resistant-enterobacteriaceae-infections
#14
Madeline King, Emily Heil, Safia Kuriakose, Tiffany Bias, Vanthida Huang, Claudine El-Beyrouty, Dorothy McCoy, Jon Hiles, Lynette Richards, Julianne Gardner, Nicole Harrington, Kenneth Biason, Jason C Gallagher
Ceftazidime-avibactam is a novel cephalosporin-beta-lactamase inhibitor combination that is active against many carbapenem-resistant Enterobacteriaceae (CRE). We describe a retrospective chart review for 60 patients who received ceftazidime-avibactam for a CRE infection. In-hospital mortality was 32%, 53% of patients had microbiological cure, and 65% had clinical success. In this severely ill population with CRE infections, ceftazidime-avibactam was an appropriate option.
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28465626/synthesis-and-biological-evaluation-of-indole-core-based-derivatives-with-potent-antibacterial-activity-against-resistant-bacterial-pathogens
#15
Wei Hong, Jingyang Li, Zhe Chang, Xiaoli Tan, Hao Yang, Yifan Ouyang, Yanhui Yang, Sargit Kaur, Ian C Paterson, Yun Fong Ngeow, Hao Wang
The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus...
July 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28377310/risk-factors-for-extended-spectrum-%C3%AE-lactamase-producing-escherichia-coli-urinary-tract-infection-in-the-community-in-denmark-a-case-control-study
#16
M Søgaard, U Heide-Jørgensen, J P Vandenbroucke, H C Schønheyder, C M J E Vandenbroucke-Grauls
OBJECTIVE: To verify the role of proton pump inhibitors (PPI) and nitrofurantoin, which have appeared as novel risk factors for carriage of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli, as risk factors for ESBL E. coli urinary tract infection (UTI). We included known risk factors to ascertain whether our findings are comparable with those of previous studies. METHODS: Population-based case-control study including 339 cases with community-onset ESBL E...
April 1, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28367020/comparison-of-four-phenotypic-methods-for-detection-of-metallo-%C3%AE-lactamase-producing-gram-negative-bacteria-in-rural-teaching-hospital
#17
Chinjal A Panchal, Sweta Sunil Oza, Sanjay J Mehta
CONTEXT: Metallo-β-lactamase (MBL)-producing bacteria lead to resistance to carbapenem an antibiotic that used as the last resort for treatment of multidrug-resistant bacteria, extended spectrum beta-lactamases, and AmpC β-lactamase-producing Gram-negative bacteria (GNB). The emergence of MBL-producing GNB is challenge to microbiology laboratories because there are no standardized guidelines available to detect them. The aim of this study was to compare four phenotypic methods to detect MBL production in GNB and to determine antibiotic sensitivity of MBL-producing isolates...
April 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28343258/variation-of-antibiotic-consumption-and-its-correlated-factors-in-turkey
#18
Ayfer Sahin, Ahmet Akici, Volkan Aydin, Bahar Melik, Mesil Aksoy, Ali Alkan
BACKGROUND: Presentation of antibiotic utilization data by reliable and comparable analyses constitutes an important way of ensuring rational use of antibiotics. This study aimed to evaluate antibiotic consumption (AC) of Turkey by each city/region and to investigate any association of such consumption with socio-economic factors. METHOD: For 81 provinces and 12 regions in Turkey, AC data from IMS (Intercontinental Medical Statistics) in 2011 was analyzed in accordance with "ATC/DDD, DID" (Anatomical Therapeutic Chemical/Defined Daily Doses, DID = DDD/1000 inhabitants/day) methodology supported by World Health Organization...
July 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28338347/ceftazidime-avibactam-novel-antimicrobial-combination-for-the-treatment-of-complicated-urinary-tract-infections
#19
Jakhongir F Alidjanov, Moritz Fritzenwanker, Ivan Hoffman, Florian M Wagenlehner
Ceftazidime-avibactam is a combination of a third-generation cephalosporin and a novel non-beta-lactam beta-lactamase inhibitor. This combination was recently recommended for the treatment of complicated urinary tract infections, including acute pyelonephritis, in adults with limited or no alternative treatment options. The current review is aimed to determine activity, efficacy and safety of ceftazidime-avibactam in the treatment of patients with complicated urinary tract infections.
March 24, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28303449/novel-beta-lactamase-inhibitors-unlocking-their-potential-in-therapy
#20
REVIEW
Darren Wong, David van Duin
Carbapenem-resistant Enterobacteriaceae are amongst the most feared pathogens due to severely limited treatment options. In response to this threat, three novel β-lactamase inhibitors have been developed in an attempt to reinvigorate and sustain our current antimicrobial therapies. Avibactam, vaborbactam, and relebactam are inhibitor agents with high affinity to Ambler class A and C β-lactamases and favorable outcomes in current clinical trials. However, although they do possess key similarities, these agents have unique differences which may have important clinical implications...
April 2017: Drugs
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