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https://www.readbyqxmd.com/read/29348810/structure-based-virtual-screening-for-the-discovery-of-novel-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#1
Francesca Spyrakis, Giuseppe Celenza, Francesca Marcoccia, Matteo Santucci, Simon Cross, Pierangelo Bellio, Laura Cendron, Mariagrazia Perilli, Donatella Tondi
Bacterial resistance has become a worldwide concern after the emergence of metallo-β-lactamases (MBLs). They represent one of the major mechanisms of bacterial resistance against beta-lactam antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 NDM-1, the most prevalent type, is extremely efficient in inactivating nearly all-available antibiotics including last resort carbapenems. No inhibitors for NDM-1 are currently available in therapy, making the spread of NDM-1 producing bacterial strains a serious menace...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29339760/biochemical-and-genetic-characterization-of-a-novel-metallo-%C3%AE-lactamase-from-marine-bacterium-erythrobacter-litoralis-htcc-2594
#2
Xia-Wei Jiang, Hong Cheng, Ying-Yi Huo, Lin Xu, Yue-Hong Wu, Wen-Hong Liu, Fang-Fang Tao, Xin-Jie Cui, Bei-Wen Zheng
Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam-based antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29336873/optimization-of-novel-monobactams-with-activity-against-carbapenem-resistant-enterobacteriaceae-identification-of-lys228
#3
Folkert Reck, Alun Bermingham, Johanne Blais, Vladimir Capka, Taryn Cariaga, Anthony Casarez, Richard Colvin, Charles R Dean, Alex Fekete, Wanben Gong, Ellie Growcott, Hongqiu Guo, Adriana K Jones, Cindy Li, Fengxia Li, Xiaodong Lin, Mika Lindvall, Sara Lopez, David McKenney, Louis Metzger, Heinz E Moser, Ramadevi Prathapam, Dita Rasper, Patrick Rudewicz, Vijay Sethuraman, Xiaoyu Shen, Jacob Shaul, Robert L Simmons, Kyuto Tashiro, Dazhi Tang, Meiliana Tjandra, Nancy Turner, Tsuyoshi Uehara, Charles Vitt, Steven Whitebread, Aregahegn Yifru, Xu Zang, Qingming Zhu
Metallo-β-lactamases (MBLs), such as New Delhi metallo-β-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of β-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine β-lactamases (SBLs), which are often co-expressed in clinical isolates...
January 4, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29332105/the-emergence-of-carbapenem-resistant-klebsiella-pneumoniae-isolates-producing-oxa-48-and-ndm-in-the-southern-asir-province-saudi-arabia
#4
Ibrahim A Al-Zahrani, Bander A Alsiri
To identify the prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and the most common types of cabapenemases among CRKP in the Southern (Asir) province hospitals, Saudi Arabia. Methods: The cross-sectional study was conducted between late April and September in 2015. A total of 54 Klebsiella pneumoniae (K. pneumoniae) isolates with reduced sensitivity to carbapenems were obtained from various clinical specimens of the 2 largest hospitals in the Southern province. Minimum inhibitory concentrations (MICs) of carbapenems were confirmed using E-test...
January 2018: Saudi Medical Journal
https://www.readbyqxmd.com/read/29296273/new-delhi-metallo-%C3%AE-lactamase-1-producing-klebsiella-pneumoniae-isolates-in-hospitalized-patients-in-kashan-iran
#5
Farzaneh Firoozeh, Zeinab Mahluji, Ehsaneh Shams, Ahmad Khorshidi, Mohammad Zibaei
Background and Objectives: New Delhi metallo-ß-lactamase (NDM) is a newly emerging metallo-ß-lactamases, which can destroy all β-lactams including carbapenems. Therefore, this study aimed at evaluating New Delhi metallo-ß-lactamase-1-production in clinical isolates of Klebsiella pneumoniae in Kashan, Iran. Materials and Methods: In a cross-sectional study, 181 K. pneumoniae isolates were collected from clinical samples of patients, who referred to Shahid Beheshi hospital in Kashan during November 2013 and October 2014...
October 2017: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/29279590/distribution-of-adeb-and-ndm-1-genes-in-multidrug-resistant-acinetobacter-baumannii-isolated-from-infected-wound-of-patients-admitted-in-a-tertiary-care-hospital-in-bangladesh
#6
M J Hasan, S M Shamsuzzaman
BACKGROUND: The adeB gene in Acinetobacter baumannii regulates the bacterial internal drug efflux pump that plays a significant role in drug resistance. The aim of our study was to determine the occurrence of adeB gene in multidrug resistant and New Delhi metallo-beta-lactamase-1 (NDM- 1) gene in imipenem resistant Acinetobacter baumannii isolated from wound swab samples in a tertiary care hospital of Bangladesh. METHODS: A total of 345 wound swab samples were tested for bacterial pathogens...
December 2017: Malaysian Journal of Pathology
https://www.readbyqxmd.com/read/29269938/the-mechanism-of-ndm-1-catalyzed-carbapenem-hydrolysis-is-distinct-from-that-of-penicillin-or-cephalosporin-hydrolysis
#7
Han Feng, Xuehui Liu, Sheng Wang, Joy Fleming, Da-Cheng Wang, Wei Liu
New Delhi metallo-β-lactamases (NDMs), the recent additions to metallo-β-lactamases (MBLs), pose a serious public health threat due to its highly efficient hydrolysis of β-lactam antibiotics and rapid worldwide dissemination. The MBL-hydrolyzing mechanism for carbapenems is less studied than that of penicillins and cephalosporins. Here, we report crystal structures of NDM-1 in complex with hydrolyzed imipenem and meropenem, at resolutions of 1.80-2.32 Å, together with NMR spectra monitoring meropenem hydrolysis...
December 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29263683/contribution-of-horizontal-gene-transfer-to-the-emergence-of-vim-4-carbapenemase-producer-enterobacteriaceae-in-kuwait
#8
Ágnes Sonnevend, Nour Yahfoufi, Akela Ghazawi, Wafaa Jamal, Vincent Rotimi, Tibor Pál
Carbapenem-resistant Enterobacteriaceae encountered in countries of the Arabian Peninsula usually produce OXA-48-like and New Delhi metallo-beta-lactamases (NDM) carbapenemases. However, a temporary increase in VIM-4-producing, clonally unrelated Enterobacteriaceae strains was described earlier in a Kuwaiti hospital. We investigated the genetic support of blaVIM-4 in six Klebsiella pneumoniae strains, one Escherichia coli, and one Enterobacter cloacae strain and compared it to that of VIM-4-producing isolates from other countries of the region...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/29229643/cystatin-9-and-c-a-novel-immunotherapy-that-protects-against-multi-drug-resistant-new-delhi-metallo-beta-lactamase-1-producing-klebsiella-pneumoniae
#9
Alex J Holloway, JiehJuen Yu, Bernard P Arulanandam, Sarah M Hoskinson, Tonyia Eaves-Pyles
Multidrug-resistant (MDR) bacterial pneumonia can induce dysregulated pulmonary and systemic inflammation leading to morbidity and mortality. Antibiotics to treat MDR pathogens do not function to modulate the extent and intensity of inflammation and can have serious side effects. Herein, we evaluate the efficacy of two human cysteine proteinase inhibitors, cystatin 9 and cystatin C, as a novel immunotherapeutic treatment to combat MDR New Delhi metallo-beta-lactamase-1 (NDM-1) producing Klebsiella pneumoniae (Kp)...
December 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29226698/in-vitro-and-in-vivo-activity-of-manuka-honey-against-ndm-1-producing-klebsiella-pneumoniae-st11
#10
Muhammad Usman Qamar, Sidrah Saleem, Mark Alexander Toleman, Muhammad Saqalein, Muhammad Waseem, Muhammad Atif Nisar, Mohsin Khurshid, Zeeshan Taj, Shah Jahan
AIM: To determine the therapeutic potential of Manuka honey against New Delhi metallo-β-lactamase-1-producing Klebsiella pneumoniae ST11 in vitro and in vivo. MATERIALS & METHODS: Carbapenamases and metallo-β-lactamases-producing K. pneumoniae ST11 isolated from blood culture was confirmed by VITEK-2® system, matrix-assisted laser desorption ionization-time of flight and multilocus sequence typing, followed by determination of minimum inhibitory concentration (μg/ml) using VITEK-2 system...
January 2018: Future Microbiology
https://www.readbyqxmd.com/read/29202600/structural-and-functional-insight-of-new-delhi-metallo-%C3%AE-lactamase-1-variants
#11
Sidra Khan, Abid Ali, Asad U Khan
New Delhi Metallo β-lactamase-1 (NDM-1) is a member of the Metallo-β-lactamase family, capable of catalyzing the hydrolysis of all β-lactam antibiotics. The rapid dissemination of NDM producers, 'superbugs', has become a worldwide concern to health workers. Seventeen different variants of NDM have been reported so far, across the world. These variants varied in their sequences either by single or multiple amino acid substitutions. This review summarizes the crystal structure of NDM and provides a comparative analysis of all variants...
December 5, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29168466/new-delhi-metallo-%C3%AE-lactamase-type-carbapenemases-producing-escherichia-coli-isolates-from-hospitalized-patients-a-pilot-study
#12
Shyam Sunder Grover, Ananya Doda, Nupur Gupta, Inderjeet Gandhoke, Jyoti Batra, Charoo Hans, Shashi Khare
BACKGROUND & OBJECTIVES: Resistances to carbapenem group of antimicrobials among Escherichia coli due to production of carbapenemases, especially the New Delhi metallo-β-lactamase (NDM) types, pose serious challenges in the treatment of infections in healthcare settings. This study was undertaken to detect NDM producing E. coli isolates from hospitalized patients with urinary tract infection (UTI). METHODS: A total of 30 non-repetitive isolates of E. coli from hospitalized patients with clinical suspicion of UTI were subjected to antimicrobial susceptibility testing...
July 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29144958/isolation-of-blandm-producing-enterobacteriaceae-in-a-public-hospital-in-salvador-bahia-brazil
#13
Maria Goreth Barberino, Silvia de Araujo Cruvinel, Célio Faria, Marco Aurélio Salvino, Márcio Oliveira
Carbapenemases have great importance in the global epidemiological scenario since infections with carbapenemase-producing bacteria are associated with high mortality, especially in hospitalized patients in intensive care units. This study describes two microorganisms producers of the New Delhi Metallo-b-lactamase (NDM), Klebsiella pneumoniae and Citrobacter freundii, from two patients admitted to a public hospital in Salvador, Bahia. These are the first clinical cases of NDM described in microorganisms in the north and northeast Brazil...
November 13, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29138303/cxc-chemokines-exhibit-bactericidal-activity-against-multidrug-resistant-gram-negative-pathogens
#14
Matthew A Crawford, Debra J Fisher, Lisa M Leung, Sara Lomonaco, Christine Lascols, Antonio Cannatelli, Tommaso Giani, Gian Maria Rossolini, Yohei Doi, David R Goodlett, Marc W Allard, Shashi K Sharma, Erum Khan, Robert K Ernst, Molly A Hughes
The continued rise and spread of antimicrobial resistance among bacterial pathogens pose a serious challenge to global health. Countering antimicrobial-resistant pathogens requires a multifaceted effort that includes the discovery of novel therapeutic approaches. Here, we establish the capacity of the human CXC chemokines CXCL9 and CXCL10 to kill multidrug-resistant Gram-negative bacteria, including New Delhi metallo-beta-lactamase-1-producing Klebsiella pneumoniae and colistin-resistant members of the family Enterobacteriaceae that harbor the mobile colistin resistance protein MCR-1 and thus possess phosphoethanolamine-modified lipid A...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29081367/first-case-of-new-delhi-metallo-%C3%AE-lactamase-in-klebsiella-pneumoniae-from-ecuador-an-update-for-south-america
#15
Daniel Romero-Alvarez, Jorge Reyes, Viviana Quezada, Carolina Satán, Nelson Cevallos, Sofía Barrera, Gabriel Trueba, Luis E Escobar, José E Villacís
OBJECTIVES: To describe a clinical case of Klebsiella pneumoniae harboring a New Delhi metallo-β-lactamase (NDM) plasmid in Ecuador and to present a map of reports of NDM isolates in South America. METHODS: The modified Hodge test, carbapenem inactivation method, imipenem-EDTA disk method (synergy), and Rapidec Carba NP test were used to identify antibiotic resistance mechanisms. The presence of resistance genes was explored with a conjugation assay, and molecular confirmation of NDM was performed by PCR and DNA sequencing...
November 15, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29064133/-double-carbapenem-and-oral-fosfomycin-for-the-treatment-of-complicated-urinary-tract-infections-caused-by-blandm-harboring-enterobacteriaceae-in-kidney-transplantation
#16
Rossana Rosa, Susan D Rudin, Laura J Rojas, Andrea M Hujer, Armando Perez-Cardona, Federico Perez, Robert A Bonomo, Octavio Martinez, Lilian M Abbo, Jose F Camargo
Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae represent an emergent problem worldwide. Treatment of infections caused by New Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly challenging as it frequently involves the use of nephrotoxic agents, which is problematic in kidney transplant recipients and non-renal transplants with marginal kidney function. We present two cases of urinary tract infections caused by NDM-harboring Enterobacteriaceae successfully treated with a combination of "double carbapenem" and oral fosfomycin...
October 24, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/29063891/identification-of-carbapenemase-mediated-resistance-among-enterobacteriaceae-bloodstream-isolates-a-molecular-study-from-india
#17
Srujana Mohanty, Mittal Gajanand, Rajni Gaind
Acquired resistance in carbapenem-resistant Enterobacteriaceae (CRE) conferred by carbapenemases is a major concern worldwide. Consecutive, non-duplicate isolates of Escherichia coli (EC) and Klebsiella pneumoniae from clinically diagnosed bloodstream infections were screened for the presence of carbapenem resistance by standard disk-diffusion method and minimum inhibitory concentration breakpoints using the Clinical and Laboratory Standards Institute guidelines. Carbapenemase-encoding genes were amplified by polymerase chain reaction...
July 2017: Indian Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29058515/prevalence-and-molecular-characterization-of-new-delhi-metallo-beta-lactamases-in-multidrug-resistant-pseudomonas-aeruginosa-and-acinetobacter-baumannii-from-india
#18
Mohibur Rahman, Kashi Nath Prasad, Shefali Gupta, Sanjay Singh, Avinash Singh, Ashutosh Pathak, Kamlesh Kumar Gupta, Saheem Ahmad, Bruno Gonzalez Zorn
New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii is a major concern. We investigated the presence of NDM and its variants in P. aeruginosa and A. baumannii at a tertiary hospital in North India. A total of 236 isolates (130 P. aeruginosa and 106 A. baumannii) were included; 38 (29.23%) P. aeruginosa and 20 A. baumannii isolates (18.8%) were resistant to carbapenems and all of them were blaNDM positive. All 38 carbapenem-resistant P. aeruginosa harbored blaNDM-1, while 12 (60%) of 20 A...
October 23, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29038264/clinical-evolution-of-new-delhi-metallo-%C3%AE-lactamase-ndm-optimizes-resistance-under-zn-ii-deprivation
#19
Guillermo Bahr, Luisina Vitor-Horen, Christopher R Bethel, Robert A Bonomo, Lisandro J González, Alejandro J Vila
Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading and taking a staggering toll on all healthcare systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family of carbapenemases are the Zn(II)-dependent β-lactamases, known as Metallo-β-lactamases (MBLs). Among them, the New-Delhi Metallo-β-lactamase (NDM) has experienced the fastest and widest geographical spread. While other clinically important MBLs are soluble periplasmic enzymes, NDM β-lactamases are lipoproteins anchored to the outer membrane in Gram-negative bacteria...
October 16, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29036990/-drug-resistance-and-dissemination-of-new-delhi-metallo-%C3%AE-lactamase-1-positive-bacteria-in-a-patient
#20
X F Zhao, M Yuan, X Chen, X F Liu, D S Yu, J Li
Objective: The aim of this work was to report the surveillance and dissemination of NDM-1 positive bacteria in a patient and ward environment. Methods: In 2010, during the therapy for a 51 years old patient, clinical and environmental samples were collected for carbapenem resistant bacterial culture, according to the clinical microbiological examination. Strains identification and antibiotic susceptibility were tested by VITEK Compact 2 system and E-test. The bla(NDM-1) was detected by PCR and analyzed by sequencing...
October 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
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