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https://www.readbyqxmd.com/read/29444952/treatment-of-infections-caused-by-extended-spectrum-beta-lactamase-ampc-and-carbapenemase-producing-enterobacteriaceae
#1
REVIEW
Jesús Rodríguez-Baño, Belén Gutiérrez-Gutiérrez, Isabel Machuca, Alvaro Pascual
Therapy of invasive infections due to multidrug-resistant Enterobacteriaceae (MDR-E) is challenging, and some of the few active drugs are not available in many countries. For extended-spectrum β-lactamase and AmpC producers, carbapenems are the drugs of choice, but alternatives are needed because the rate of carbapenem resistance is rising. Potential active drugs include classic and newer β-lactam-β-lactamase inhibitor combinations, cephamycins, temocillin, aminoglycosides, tigecycline, fosfomycin, and, rarely, fluoroquinolones or trimethoprim-sulfamethoxazole...
April 2018: Clinical Microbiology Reviews
https://www.readbyqxmd.com/read/29442147/-urosepsis
#2
Mathias W Pletz, Sebastian Weis, Christina Forstner, Florian Wagenlehner
Urosepsis is defined as a severe disease due to organ failure caused by a urinary tract infection. An empirical antibiotic therapy should be instigated within the first hour after diagnosis. Urine cultures and blood cultures should be performed before antibiotic treatment. Further diagnostics should be carried out at an early stage to enable an interventional focus control in the case of urinary tract obstruction or abscess formation, if necessary. Gram-negative pathogens are most frequently isolated. Extended spectrum beta-lactamase (ESBL) forming bacteria as a cause of urosepsis are increasing...
February 7, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/29432937/detection-of-vim-2-imp-1-and-ndm-1-producing-multidrug-resistant-pseudomonas-aeruginosa-in-malaysia
#3
Siew Mun Liew, Ganeswrei Rajasekaram, Savithri D Puthucheary, Kek Heng Chua
OBJECTIVES: The increasing incidence of carbapenem-resistant Pseudomonas aeruginosa along with the discovery of novel metallo-β-lactamases (MBLs) is of concern. In this study, the isolation of Malaysian MBL-producing P. aeruginosa clinical strains was investigated. METHODS: Fifty-three P. aeruginosa clinical strains were isolated from different patients in Sultanah Aminah Hospital, Johor Bahru, Malaysia in 2015. Antimicrobial susceptibility test was conducted. Minimum inhibitory concentrations (MICs) of imipenem and meropenem were determined by Etest...
February 9, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29427523/meropenem-and-vaborbactam-stepping-up-the-battle-against-carbapenem-resistant-enterobacteriaceae
#4
Sarah Christina Jane Jorgensen, Michael Joseph Rybak
Vaborbactam (VAB; formerly RPX7009) is a novel beta-lactamase inhibitor based on a cyclic boronic acid pharmacophore with potent inhibitory activity against Ambler class A and C beta-lactamases. It has been co-formulated with meropenem to restore its activity against Klebsiella pneumoniae carbapenemases (KPC). VAB does not inhibit class B or D carbapenemases, nor does it improve the activity of meropenem against multidrug-resistant non-fermenting Gram-negative bacilli, notably Acinetobacter spp. and Pseudomonas aeruginosa...
February 10, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29422890/embelin-restores-carbapenem-efficacy-against-ndm-1-positive-pathogens
#5
Nian-Zhi Ning, Xiong Liu, Fanghong Chen, Peng Zhou, Lihong Hu, Jian Huang, Zhan Li, Jie Huang, Tao Li, Hui Wang
The emergence and spread of carbapenemase in Gram-negative pathogens poses an enormous threat to global public health. New Delhi metallo-β-lactamase-1 (NDM-1) inactivates nearly every class of β-lactam antibiotics, including carbapenem; however, there is no clinically useful NDM-1 inhibitor. Embelin, an important ingredient in traditional herbal medicine, has anti-tumor effects. The current study is the first to discover and examine the inhibitory activity of embelin against β-lactamase NDM-1. The IC50 of embelin was 2...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29373087/an-outbreak-of-ndm-1-producing-klebsiella-pneumoniae-associated-with-ompk35-and-ompk36-porin-loss-in-tunisia
#6
Zaineb Hamzaoui, Alain Ocampo-Sosa, Elaa Maamar, Marta Fernandez Martinez, Sana Ferjani, Samia Hammami, Sarra Harbaoui, Nathalie Genel, Guillaume Arlet, Mabrouka Saidani, Amine Slim, Ilhem Boutiba-Ben Boubaker, Luis Martinez-Martinez
OBJECTIVES: To describe clinical and molecular characteristics of an outbreak due to metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae collected at Charles Nicolle Hospital of Tunis and to analyze the impact of outer membrane porin (OMP) loss on carbapenem resistance levels. METHODS: Between 2010 and 2015, 178 carbapenem-resistant Enterobacteriaceae were isolated. Screening for MBL production was performed using combined disk diffusion method, with imipenem and ethylene diamine tetraacetic acid (EDTA) as inhibitors...
January 26, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29358299/shaping-substrate-selectivity-in-a-broad-spectrum-metallo-%C3%AE-lactamase
#7
Lisandro J González, Cintia Stival V, Juan L Puzzolo, Diego M Moreno, Alejandro J Vila
Metallo-β-lactamases (MBLs) are the major group of carbapenemases produced by bacterial pathogens. The design of MBL inhibitors has been limited, among other issues, by the incomplete knowledge about how these enzymes modulate substrate recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive carbapenemases. This narrower substrate profile has been attributed to a sequence insertion present in B2 enzymes that limits the accessibility to the active site. In this work, we evaluate the role of sequence insertions naturally occurring in the B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1...
January 22, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29356380/phenyl-boronic-acids-development-led-to-validated-leads-active-in-clinical-strains-overexpressing-kpc-2-a-step-against-bacterial-resistance
#8
Giuseppe Celenza, Mattia Vicario, Pierangelo Bellio, Linciano Pasquale, Mariagrazia Perilli, Antonio Oliver, Jesus Blazquez, Laura Cendron, Donatella Tondi
The emergence and dissemination of multi drug resistant (MDR) pathogens resistant to near all available antibiotics poses a significant threat in clinical therapy. Among them, Klebsiella pneumoniae clinical isolates overexpressing KPC-2 carbapenemase are the most worrisome, extending bacterial resistance to last resort carbapenems. In this study we investigate the molecular recognition requirements in KPC-2 active site by small phenyl boronic acid derivatives. Four new phenyl boronic acid derivatives were designed and tested vs KPC-2...
January 22, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29322236/-urosepsis
#9
Mathias W Pletz, Sebastian Weis, Christina Forstner, Florian Wagenlehner
Urosepsis is defined as a severe disease due to organ failure caused by a urinary tract infection. An empirical antibiotic therapy should be instigated within the first hour after diagnosis. Urine cultures and blood cultures should be performed before antibiotic treatment. Further diagnostics should be carried out at an early stage to enable an interventional focus control in the case of urinary tract obstruction or abscess formation, if necessary. Gram-negative pathogens are most frequently isolated. Extended spectrum beta-lactamase (ESBL) forming bacteria as a cause of urosepsis are increasing...
January 10, 2018: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29311069/meropenem-vaborbactam-single-dose-pharmacokinetics-and-safety-in-subjects-with-chronic-renal-impairment
#10
Christopher M Rubino, Sujata M Bhavnani, Jeffery S Loutit, Brooke Lohse, Michael N Dudley, David C Griffith
Vaborbactam is a member of a new class of β-lactamase inhibitors with inhibitory activity against serine carbapenemases (e.g. Klebsiella pneumoniae carbapenemase) that has been developed in combination with meropenem. Pharmacokinetics of the combination were evaluated in 41 subjects with chronic renal impairment in a Phase 1, open-label, single-dose study. Subjects were assigned to one of five groups based on renal function: normal (creatinine clearance ≥90 mL/min), mild (estimated glomerular filtration rate [eGFR] 60-89 mL/min/1...
January 8, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29276104/determination-of-mic-and-disk-diffusion-quality-control-guidelines-for-meropenem-vaborbactam-a-novel-carbapenem-boronic-acid-%C3%AE-lactamase-inhibitor-combination
#11
Erik Munson, Michael D Huband, Mariana Castanheira, Kelley A Fedler, Robert K Flamm
Meropenem-vaborbactam is a carbapenem/cyclic boronic acid β-lactamase inhibitor combination primarily active against Gram-negative bacilli, including those harboring class A serine carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC). A Clinical and Laboratory Standards Institute M23-A4 (Tier 2) quality control study established broth microdilution and disk diffusion ranges for reference strains. Two KPC-producing K. pneumoniae ATCC strains are recommended for quality control testing.
December 5, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29274802/susceptibility-testing-and-detection-of-%C3%AE-lactam-resistance-mechanisms-in-enterobacteriaceae-a-multicentre-national-proficiency-study
#12
María Díez-Aguilar, María-Carmen Conejo, María-Isabel Morosini, Núria Tormo Palop, Concepción Gimeno, Rafael Cantón, Álvaro Pascual
A nationwide study was developed to evaluate the ability of 60 Spanish clinical microbiology laboratories to predict the underlying β-lactam resistance mechanisms of 12 Enterobacteriaceae strains (CCS01-CCS12). Results obtained by two reference laboratories were compared with those reported by the participants that used their own routine susceptibility testing methodology. CLSI interpretive criteria were used in 53.3% of the centres, while 46.7% used EUCAST. The overall categorical agreement (CA) was 85.5%...
December 21, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29232103/game-changers-new-%C3%AE-lactamase-inhibitor-combinations-targeting-antibiotic-resistance-in-gram-negative-bacteria
#13
Karen Bush
Recent regulatory approvals for the β-lactam inhibitor combinations of ceftazidime-avibactam and meropenem-vaborbactam have provided two novel therapeutic options for the treatment of multidrug-resistant infections caused by Gram-negative bacteria. Most importantly, these combination agents have satisfied an important medical need related to antibiotic-resistant Klebsiella pneumoniae that produce serine carbapenemases, especially the Klebsiella pneumoniae carbapenemase (KPC) enzymes. Both combinations contain non-β-lactam β-lactamase inhibitors of novel chemical classes not previously developed as antibacterial agents, the diazabicyclooctanes and cyclic boronic acid derivatives...
December 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29230684/imipenem-relebactam-and-meropenem-vaborbactam-two-novel-carbapenem-%C3%AE-lactamase-inhibitor-combinations
#14
REVIEW
George G Zhanel, Courtney K Lawrence, Heather Adam, Frank Schweizer, Sheryl Zelenitsky, Michael Zhanel, Philippe R S Lagacé-Wiens, Andrew Walkty, Andrew Denisuik, Alyssa Golden, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Relebactam (formerly known as MK-7655) is a non-β-lactam, bicyclic diazabicyclooctane, β-lactamase inhibitor that is structurally related to avibactam, differing by the addition of a piperidine ring to the 2-position carbonyl group. Vaborbactam (formerly known as RPX7009) is a non-β-lactam, cyclic, boronic acid-based, β-lactamase inhibitor. The structure of vaborbactam is unlike any other currently marketed β-lactamase inhibitor. Both inhibitors display activity against Ambler class A [including extended-spectrum β-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs)] and class C β-lactamases (AmpC)...
December 12, 2017: Drugs
https://www.readbyqxmd.com/read/29228202/activity-of-ceftazidime-avibactam-against-problem-enterobacteriaceae-and-pseudomonas-aeruginosa-in-the-uk-2015-16
#15
David M Livermore, Danièle Meunier, Katie L Hopkins, Michel Doumith, Robert Hill, Rachel Pike, Peter Staves, Neil Woodford
Background: Ceftazidime/avibactam combines an established oxyimino-cephalosporin with the first diazabicyclooctane β-lactamase inhibitor to enter clinical use. We reviewed its activity against Gram-negative isolates, predominantly from the UK, referred for resistance investigation in the first year of routine testing, beginning in July 2015. Methods: Isolates were as received from referring laboratories; there is a bias to submit those with suspected carbapenem resistance...
December 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29216350/italian-nationwide-survey-on-pseudomonas-aeruginosa-from-invasive-infections-activity-of-ceftolozane-tazobactam-and-comparators-and-molecular-epidemiology-of-carbapenemase-producers
#16
Tommaso Giani, Fabio Arena, Simona Pollini, Vincenzo Di Pilato, Marco Maria D'Andrea, Lucia Henrici De Angelis, Matteo Bassetti, Gian Maria Rossolini
Objectives: Pseudomonas aeruginosa is a major cause of severe healthcare-associated infections and often shows MDR phenotypes. Ceftolozane/tazobactam is a new cephalosporin/β-lactamase inhibitor combination with potent activity against P. aeruginosa. This survey was carried out to evaluate the susceptibility of P. aeruginosa, circulating in Italy, to ceftolozane/tazobactam and comparators and to investigate the molecular epidemiology of carbapenemase-producing strains. Methods: Consecutive non-replicate P...
December 5, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29186432/bacterial-zincophore-s-s-ethylenediamine-n-n-disuccinic-acid-is-an-effective-inhibitor-of-mbls
#17
Anna Proschak, Jan Kramer, Ewgenij Proschak, Thomas A Wichelhaus
Objectives: Carbapenemases such as MBLs are spreading among Gram-negative bacterial pathogens. Infections due to these MDR bacteria constitute a major global health challenge. Therapeutic strategies against carbapenemase-producing bacteria include β-lactamase inhibitor combinations. [S,S]-ethylenediamine-N,N'-disuccinic acid (EDDS) is a chelator and potential inhibitor of MBLs. We investigated the activity of EDDS in combination with imipenem against MBL-producing bacteria in vitro as well as in vivo...
November 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29144958/isolation-of-blandm-producing-enterobacteriaceae-in-a-public-hospital-in-salvador-bahia-brazil
#18
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/29133551/copper-ions-and-coordination-complexes-as-novel-carbapenem-adjuvants
#19
Karrera Y Djoko, Maud E S Achard, Minh-Duy Phan, Alvin W Lo, Manfredi Miraula, Sasiprapa Prombhul, Steven J Hancock, Kate M Peters, Hanna Sidjabat, Patrick N Harris, Nataša Mitić, Timothy R Walsh, Gregory J Anderson, William M Shafer, David L Paterson, Gerhard Schenk, Alastair G McEwan, Mark A Schembri
Carbapenem-resistant Enterobacteriaceae are an urgent threat to global human health. These organisms produce β-lactamases with carbapenemase activity, such as the metallo-β-lactamase NDM-1, which is notable due to its association with mobile genetic elements and the lack of a clinically useful inhibitor. Here we examined the ability of copper to inhibit the activity of NDM-1 and explored the potential of a copper coordination complex as a mechanism to efficiently deliver copper as an adjuvant in clinical therapeutics...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29115680/mastdiscs-combi-carba-plus-a-simple-discrimination-method-for-carbapenemase-producing-enterobacteriaceae-including-oxa-48-type-producers
#20
Yusuke Ohsaki, Ryoichi Kubo, Jonathan Hobson, Mya Davies, Shunsuke Osaka, Wataru Hayashi, Yui Taniguchi, Shota Koide, Yukiko Nagano, Noriyuki Nagano
Not only detection of carbapenemases but also identification of their types accurately and rapidly in Enterobacteriaceae is still a major challenge for clinical laboratories in order to prevent the intrusion and the transmission of carbapenemase-producing Enterobacteriaceae. This study aimed to evaluate the performance of the MASTDISCS® combi Carba plus disc system in the identification of different carbapenemase types, including OXA-48-type carbapenemase for which no specific enzyme inhibitors have so far been available...
November 8, 2017: Microbiology and Immunology
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