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https://www.readbyqxmd.com/read/30022668/synthesis-and-preclinical-evaluation-of-tpa-based-zinc-chelators-as-metallo-%C3%AE-lactamase-inhibitors
#1
Christian Schnaars, Geir Kildahl-Andersen, Anthony Prandina, Roya Popal, Sylvie Large Radix, Marc Le Borgne, Tor Gjoen, Adriana Magalhães Santos Andresen, Adam Heikal, Ole Andreas Økstad, Christopher Fröhlich, Ørjan Samuelsen, Silje Lauksund, Lars Petter Jordheim, Pål Rongved, Ove Alexander Høgmoen Åstrand
The rise of antimicrobial resistance (AMR) worldwide and the increasing spread of multidrug resistant organisms expressing metallo-β-lactamases (MBL) require the development of efficient and clinically available MBL inhibitors. At present, no such inhibitor is available, and research is urgently needed to advance this field. We report herein the development, synthesis and biological evaluation of chemical compounds based on the selective zinc chelator tris-picolylamine (TPA) that can restore the bactericidal activity of meropenem (MEM) against Pseudomonas aeruginosa and Klebsiella pneumoniae expressing the carbapenemases Verona integron-encoded metallo-β-lactamase (VIM-2) and New Delhi metallo-β-lactamase 1 (NDM-1), respectively...
July 19, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/30021742/two-for-the-price-of-one-emerging-carbapenemases-in-a-returning-traveller-to-new-york-city
#2
Jaimie Mittal, Wendy A Szymczak, Yi Guo, Michael H Levi, Liang Chen, Barry N Kreiswirth, Paul F Riska, Priya Nori
We report a case of a complex orthopaedic infection in a patient returning to New York City from Bangladesh where he was involved in a serious motor vehicle accident. He developed extensive osteomyelitis with a carbapenem-resistant Klebsiella pneumoniae The isolate was unique due to the coexistence of New Delhi metallo-β-lactamase-1 and Oxacillinase type-181 carbapenemases, which are relatively uncommon in North America and were presumably acquired in Bangladesh. Herein, we explore challenges associated with management of carbapenem-resistant Enterobacteriaceae infections, including limited available data on effective antimicrobial therapy...
July 18, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/30019584/correction-to-dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#3
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
No abstract text is available yet for this article.
July 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29997749/first-detection-of-new-delhi-metallo-%C3%AE-lactamases-variants-ndm-1-ndm-2-among-pseudomonas-aeruginosa-isolated-from-iraqi-hospitals
#4
Sarah Jehad Ismail, Suhad Saad Mahmoud
Background and Objectives: Multidrug resistance and in particular, carbapenem resistant Gram-negative bacteria is spreading worldwide at an alarming rate. Among the clinically significant carbapenemases, the New Delhi Metallo-β-lactamase (NDM) is one of the most formidable. NDM efficiently hydrolyses β-lactams and is the last-resort among carbapenems. Hence, therapeutic options for NDM producer bacteria become restricted to a handful of antibiotics. The present study was undertaken to detect the prevalence of the bla NDM -variants Metallo β-lactamases (MBLs) among isolates of Pseudomonas aeruginosa recovered from various clinical samples of hospitalized patients in Baghdad, Iraq...
April 2018: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/29991384/sharing-more-than-friendship-transmission-of-ndm-5-st167-and-ctx-m-9-st69-escherichia-coli-between-dogs-and-humans-in-a-family-finland-2015
#5
Thomas Grönthal, Monica Österblad, Marjut Eklund, Jari Jalava, Suvi Nykäsenoja, Katariina Pekkanen, Merja Rantala
IntroductionCarbapenemase-producing Enterobacteriaceae (CPE) have rarely been reported in dogs, and never in animals in Finland. However, in April 2015, two meropenem-resistant Escherichia coli were identified from two dogs in one family. Both dogs suffered from chronic otitis externa . Methods: Epidemiological and molecular investigations (pulsed-field gel electrophoresis (PFGE), multilocus sequence typing) were conducted to investigate the source of infection and transmission routes. Results: In both dogs and one family member New Delhi metallo-beta-lactamase (NDM-5)-producing multidrug-resistant ST167 E...
July 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29972555/prevalence-of-metallo-%C3%AE-lactamase-encoding-genes-among-carbapenem-resistant-pseudomonas-aeruginosa-strains-isolated-from-burn-patients-in-iran
#6
Fereshteh Jabalameli, Elahe Taki, Mohammad Emaneini, Reza Beigverdi
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been considered a major cause of infection and mortality in burn patients, especially in developing countries such as Iran. One of the most common mechanisms of carbapenem resistance is production of metallo-β-lactamases [(MBLs), including Verona Integron-encoded Metallo-beta-lactamase (VIM), imipenemase (IMP), São Paulo metalo-beta-lactamase (SPM), German imipenemase (GIM), New Delhi metallo-beta-lactamase (NDM), Dutch imipenemase (DIM), Adelaide imipenemase (AIM), Seoul imipenemase (SIM), KHM, Serratia metallo-β-lactamase (SMB), Tripoli metallo-β-lactamase (TMB), and Florence imipenemase (FIM)]...
May 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29966917/synthesis-and-antibacterial-bioactivities-of-cationic-deacetyl-linezolid-amphiphiles
#7
Peng-Yan Bai, Shang-Shang Qin, Wen-Chao Chu, Yi Yang, De-Yun Cui, Yong-Gang Hua, Qian-Qian Yang, En Zhang
Bacterial infections cause various life-threatening diseases and have become a serious public health problem due to the emergence of drug-resistant strains. Thus, novel antibiotics with excellent antibacterial activity and low cytotoxicity are urgently needed. Here, three series of novel cationic deacetyl linezolid amphiphiles bearing one lipophilic alkyl chain and one non-peptidic amide bond were synthesized and tested for antimicrobial activities. Several compounds showed excellent antibacterial activity toward drug-sensitive bacteria such as gram-negative bacteria Escherichia coli (E...
June 23, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29958975/first-report-of-extremely-drug-resistant-proteus-mirabilis-isolate-carrying-plasmid-mediated-bla-ndm-1-in-a-tunisian-intensive-care-unit
#8
Kanzari Lamia, Ferjani Sana, Saidani Mabrouka, Hamzaoui Zeineb, Jendoubi Ali, Harbaoui Sarra, Ferjani Asma, Rehaiem Amel, Boutiba Ben Boubaker Ilhem, Slim Amine
Emergence of the New Delhi metallo-β-lactamase (NDM-1), an Ambler class B metallo-β-lactamase (MBL) able to hydrolyze all β-lactams, except monobactams constitutes a critical and growingly important medical issue. The acquisition of blaNDM-1 is of a special concern with P. mirabilis that is intrinsically resistant to tetracycline, tigecycline and colistin, which will make clinical treatment extremely difficult. Here we described, for the first time, blaNDM-1 gene in an extensively drug resistant (XDR) P...
June 26, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29909397/evolution-of-new-delhi-metallo-%C3%AE-lactamase-ndm-in-the-clinic-effects-of-ndm-mutations-on-stability-zinc-affinity-mono-zinc-activity
#9
Zishuo Cheng, Pei W Thomas, Lincheng Ju, Alexander Bergstrom, Kelly Mason, Delaney Clayton, Callie Miller, Christopher R Bethel, Jamie VanPelt, David L Tierney, Richard C Page, Robert A Bonomo, Walter Fast, Michael W Crowder
Infections by carbapenem-resistant Enterobacteriaceae (CRE) are difficult to manage owing to broad antibiotic resistance profiles and because of the inability of clinically-used β-lactamase inhibitors to counter the activity of metallo-β-lactamases often harbored by these pathogens. Of particular importance is New Delhi metallo-β-lactamase (NDM), which requires a dinuclear zinc ion cluster for catalytic activity. Here, we compare the structures and functions of clinical NDM variants 1-17. The impact of NDM variants on structure is probed by comparing comparing melting temperature and refolding efficiency and also by spectroscopy (UV-Vis, 1 H-NMR, and EPR) of di-cobalt metalloforms...
June 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29787365/kpc-2-producing-st101-klebsiella-pneumoniae-from-bloodstream-infection-in-india
#10
Chaitra Shankar, Baby Abirami Shankar, Abi Manesh, Balaji Veeraraghavan
This study characterizes KPC-2 producing Klebsiella pneumoniae belonging to ST101. Whole genome sequencing using the Ion Torrent PGM platform with 400 bp chemistry was performed. blaKPC-2 was found on an IncFIIK plasmid associated with ISKpn6 and ISKpn7 without Tn4401. This is the first report of KPC-2 K. pneumoniae from bacteremia in India. The isolate also coded for other resistance genes such as aadA1, aadA2, armA, aac(3)-Ild, aac(6')-Ild for aminoglycoside; blaSHV-11, blaTEM-1B, blaOXA-9, for β-lactams and aac(6')-Ild, oqxA, oqxB, qnrB1 for fluoroquinolones...
May 22, 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29774858/genomic-epidemiology-of-global-carbapenemase-producing-enterobacter-spp-2008-2014
#11
Gisele Peirano, Yasufumi Matsumura, Mark D Adams, Patricia Bradford, Mary Motyl, Liang Chen, Barry N Kreiswirth, Johann D D Pitout
We performed whole-genome sequencing on 170 clinical carbapenemase-producing Enterobacter spp. isolates collected globally during 2008-2014. The most common carbapenemase was VIM, followed by New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae carbapenemase, oxacillin 48, and IMP. The isolates were of predominantly 2 species (E. xiangfangensis and E. hormaechei subsp. steigerwaltii) and 4 global clones (sequence type [ST] 114, ST93, ST90, and ST78) with different clades within ST114 and ST90. Particular genetic structures surrounding carbapenemase genes were circulating locally in various institutions within the same or between different STs in Greece, Guatemala, Italy, Spain, Serbia, and Vietnam...
June 2018: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29760136/aztreonam-avibactam-combination-restores-susceptibility-of-aztreonam-in-dual-carbapenemase-producing-enterobacteriaceae
#12
Ka Lip Chew, Michelle K L Tay, Bernadette Cheng, Raymond T P Lin, Sophie Octavia, Jeanette W P Teo
Newly approved Food and Drug Administration (FDA) β-lactam-β-lactamase inhibitor (βL-βLI) inhibitor combinations such as ceftazidime-avibactam and meropenem-vaborbactam are potent inhibitors of class A carbapenemase (typified by KPC [ Klebsiella pneumoniae carbapenemase]-like) (1, 2) but are ineffective against carbapenemase-producing Enterobacteriaceae (CPE) producing class B metallo-β-lactamases (MβLs) such as New Delhi metallo-β-lactamase (NDM) (1-4).….
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29749367/use-of-succinic-oxalic-acid-in-reducing-the-dosage-of-colistin-against-new-delhi-metallo-%C3%AE-lactamase-1-bacteria
#13
Ravichandiran Kumar, Brinda Chandar, Madasamy Parani
Background & objectives: New Delhi metallo-β-lactamase 1 (NDM-1) cleaves the beta-lactam ring, and confers bacterial resistance against most of the beta-lactam antibiotics, except tigecycline and colistin. Among these two antibiotics, colistin is considered toxic, and therefore, its clinical use and dosage need cautious approach. In the present study, six organic acids were screened individually and in combination of two acids for their effectiveness against NDM-1 Escherichia coli and a combination of colistin and oxalic or succinic acid was tested to find out the potential of combination therapy for reducing the dose of toxic colistin...
January 2018: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/29749296/molecular-and-computational-approaches-to-understand-resistance-of-new-delhi-metallo-%C3%AE-lactamase-variants-ndm-1-ndm-4-ndm-5-ndm-6-ndm-7-producing-strains-against-carbapenems
#14
Abid Ali, Divya Gupta, Gaurava Srivastava, Ashok Sharma, Asad U Khan
The discovery of NDM-1 and its variants has caused the emergence of antibiotic resistance in the community and hospital setting, causing major concern for health care across the globe. New Delhi Metallo-β-lactamase is known to hydrolyze almost all β-lactam antibiotics. Studies have shown the hydrolytic activates of NDM-1 and some of its variants, however a comparative study of these NDM variants has not been explored in detail. Hence, we proposed to check their catalytic activity by performing a comparative study between NDM-1 and its variants...
May 11, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29726673/vancomycin-analogue-restores-meropenem-activity-against-ndm-1-gram-negative-pathogens
#15
Venkateswarlu Yarlagadda, Paramita Sarkar, Sandip Samaddar, Goutham Belagula Manjunath, Susweta Das Mitra, Krishnamoorthy Paramanandham, Bibek Ranjan Shome, Jayanta Haldar
New Delhi metallo-β-lactamase-1 (NDM-1) is the major contributor to the emergence of carbapenem resistance in Gram-negative pathogens (GNPs) and has caused many clinically available β-lactam antibiotics to become obsolete. A clinically approved inhibitor of metallo-β-lactamase (MBL) that could restore the activity of carbapenems against resistant GNPs has not yet been found, making NDM-1 a serious threat to human health. Here, we have rationally developed an inhibitor for the NDM-1 enzyme, which has the ability to penetrate the outer membrane of GNPs and inactivate the enzyme by depleting the metal ion (Zn2+ ) from the active site...
July 13, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29713466/dissemination-of-bla-ndm-5-gene-via-an-incx3-type-plasmid-among-non-clonal-escherichia-coli-in-china
#16
Xi Li, Ying Fu, Mengyuan Shen, Danyan Huang, Xiaoxing Du, Qingfeng Hu, Yonglie Zhou, Dairong Wang, Yunsong Yu
Background: The emergence and spread of New Delhi metallo-β-lactamase-producing Enterobacteriaceae has been a serious challenge to manage in the clinic due to its rapid dissemination of multi-drug resistance worldwide. As one main type of carbapenemases, New Delhi metallo-β-lactamase (NDM)is able to confer resistance to almost all β-lactams, including carbapenems, in Enterobacteriaceae . Recently, New Delhi metallo-β-lactamase-5 attracted extensive attention because of increased resistance to carbapenems and widespread dissemination...
2018: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/29708847/preliminary-study-on-the-antibacterial-activity-of-essential-oils-alone-and-in-combination-with-gentamicin-against-extended-spectrum-%C3%AE-lactamase-producing-and-new-delhi-metallo-%C3%AE-lactamase-1-producing-klebsiella-pneumoniae-isolates
#17
Paweł Kwiatkowski, Agata Pruss, Bartłomiej Grygorcewicz, Bartosz Wojciuk, Barbara Dołęgowska, Stefania Giedrys-Kalemba, Ewa Kochan, Monika Sienkiewicz
AIM: The aim of the study was to investigate possible synergistic effects between several selected, commercially available essential oils and gentamicin against extended-spectrum β-lactamase (ESBL)-producing and New Delhi metallo-β-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae isolates. MATERIALS AND METHODS: ESBLs production was confirmed by double-disk synergy test. Isolates positive for blaNDM-1 gene were found among the tested strains. K. pneumoniae ATCC® BAA-1705™ strain was used as a control...
April 30, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29692579/molecular-characterization-and-antimicrobial-susceptibility-profile-of-new-delhi-metallo-beta-lactamase-1-producing-escherichia-coli-among-hospitalized-patients
#18
Anjali Agarwal, Jyoti Srivastava, Ujjwal Maheshwari, Mohd Iftikhar
BACKGROUND: Carbapenemase-producing microorganisms are becoming a major concern among hospital-acquired infections. There is also increased multidrug resistance seen among these isolates. AIMS: We have conducted this study to determine the prevalence of New Delhi metallo-beta-lactamase-1 (NDM-1) gene-producing Escherichia coli among hospitalized patients in a tertiary care hospital in Northern India. SETTINGS AND DESIGN: The study was conducted in the Department of Microbiology with the tertiary care hospital settings...
April 2018: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/29666548/inhibitory-effect-of-soy-saponins-on-the-activity-of-%C3%AE-lactamases-including-new-delhi-metallo-%C3%AE-lactamase-1
#19
Hitoshi Horie, Asuka Chiba, Shigeo Wada
β-Lactamase-producing bacteria encode enzymes that inactivate β-lactam antibiotics by catalyzing the hydrolysis of the β-lactam ring. Crude soy saponins were observed to have synergistic effects on the antimicrobial activity of β-lactam antibiotics against β-lactamase-producing Staphylococcus aureus strains. Furthermore, the activities of β-lactamases derived from Enterobacter cloacae , Escherichia coli , and S. aureus were decreased significantly in the presence of crude soy saponins. This inhibitory effect was also observed against the New Delhi metallo-β-lactamase 1 (NDM-1), an enzyme whose activity is not inhibited by the current β-lactamase inhibitors...
May 2018: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/29656053/novel-variant-ndm-11-and-other-ndm-1-variants-in-multidrug-resistant-escherichia-coli-from-south-india
#20
Mohibur Rahman, Chiranjay Mukhopadhyay, Ravi Prakash Rai, Sanjay Singh, Shefali Gupta, Avinash Singh, Ashutosh Pathak, Kashi Nath Prasad
OBJECTIVE: New Delhi metallo-β-lactamase (NDM-1) and its variants mediated carbapenem resistance has raised a major public health concern worldwide. In the present study, we report Escherichia coli positive novel variant i.e. NDM-11 for the first time METHODS: blaNDM were investigated in E. coli by PCR and sequencing. The blaNDM variants were further characterized. The susceptibility patterns of novel blaNDM-11 towards different antibiotics were compared with blaNDM-1 by cloning expressing in E...
April 12, 2018: Journal of Global Antimicrobial Resistance
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