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Avibactam

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https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#1
Anna Both, Henning Büttner, Jiabin Huang, Markus Perbandt, Cristina Belmar Campos, Martin Christner, Florian P Maurer, Stefan Kluge, Christina König, Martin Aepfelbacher, Dominic Wichmann, Holger Rohde
Background: Avibactam is a novel broad-range β-lactamase inhibitor active against Ambler class A (including ESBL and KPC) and some Ambler class C and D (e.g. OXA-48) enzymes. We here report on the emergence of ceftazidime/avibactam resistance in clinical, multiresistant, OXA-48 and CTX-M-14-producing Klebsiella pneumoniae isolate DT12 during ceftazidime/avibactam treatment. Methods and results: Comparative whole-genome sequence analysis identified two SNPs in the CTX-M-14-encoding gene leading to two amino acid changes (P170S and T264I)...
June 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28630202/identifying-spectra-of-activity-and-therapeutic-niches-for-ceftazidime-avibactam-and-imipenem-relebactam-against-carbapenem-resistant-enterobacteriaceae
#2
Ghady Haidar, Cornelius J Clancy, Liang Chen, Palash Samanta, Ryan K Shields, Barry N Kreiswirth, M Hong Nguyen
We determined imipenem, imipenem-relebactam, ceftazidime and ceftazidime-avibactam minimum inhibitory concentrations (MICs) against 100 CRE isolates that underwent whole genome sequencing. KPCs were the most common carbapenemases. Forty-six isolates carried ESBLs. With the addition of relebactam, imipenem susceptibility increased from 8% to 88%. With the addition of avibactam, ceftazidime susceptibility increased from 0% to 85%. Neither imipenem-relebactam nor ceftazidime-avibactam was active against MBL-producers...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630192/in-vitro-activity-of-aztreonam-avibactam-against-enterobacteriaceae-and-pseudomonas-aeruginosa-isolated-by-clinical-laboratories-in-40-countries-from-2012-to-2015
#3
James A Karlowsky, Krystyna M Kazmierczak, Boudewijn L M de Jonge, Meredith A Hackel, Daniel F Sahm, Patricia A Bradford
The combination of the monobactam, aztreonam, and the non-β-lactam β-lactamase inhibitor, avibactam, is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing Enterobacteriaceae, a difficult to treat subtype of carbapenem-resistant Enterobacteriaceae for which therapeutic options are currently very limited. The present study tested clinically significant isolates of Enterobacteriaceae (n=51,352) and Pseudomonas aeruginosa (n=11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for in vitro susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using standard broth microdilution methodology...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28630191/ceftazidime-avibactam-and-aztreonam-an-interesting-strategy-to-overcome-%C3%AE-lactam-resistance-conferred-by-metallo-%C3%AE-lactamases-in-enterobacteriaceae-and-pseudomonas-aeruginosa
#4
Benjamin Davido, Lesly Fellous, Christine Lawrence, Virginie Maxime, Martin Rottman, Aurélien Dinh
We have read with great interest Marshal S. et al. regarding the efficacy of the ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) combination on metallo- β -lactamases producing Enterobacteriaceae (1).….
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28610832/comparison-of-antimicrobial-activity-between-ceftolozane-tazobactam-and-ceftazidime-avibactam-against-multidrug-resistant-isolates-of-escherichia-coli-klebsiella-pneumoniae-and-pseudomonas-aeruginosa
#5
Adnan Alatoom, Hashim Elsayed, Karen Lawlor, Laila AbdelWareth, Rania El-Lababidi, Lysettee Cardona, Mohammad Mooty, Maria-Fernanda Bonilla, Ahmad Nusair, Imran Mirza
OBJECTIVE: We compared the activity of ceftolozane-tazobactam and ceftazidime-avibactam against 120 strains including extended spectrum β-lactamase (ESBL) producers, carbapenem-resistant Enterobacteriaceae (CRE) and Pseudomonas aeruginosa isolated from patients admitted to Cleveland Clinic Abu Dhabi, United Arab Emirates. METHODS: The in-vitro susceptibility was tested using E-strip MIC method and PCR was used to characterize the carbapenemase enzymes produced by CRE strains...
June 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28602518/synergistic-activity-of-ceftazidime-avibactam-and-aztreonam-against-serine-and-metallo-%C3%AE-lactamase-producing-gram-negative-pathogens
#6
Eric Wenzler, Matthew F Deraedt, Amanda T Harrington, Larry H Danizger
This study assessed the in vitro synergy between ceftazidime, aztreonam, and ceftazidime-avibactam against serine and metallo-β-lactamase (MBL)-producing pathogens via the Etest MIC:MIC ratio and Agar-Etest synergy methods. The combination of aztreonam and ceftazidime-avibactam was synergistic against all Enterobacteriaceae. None of the tested combinations were consistently synergistic against IMP-producing P. aeruginosa.
May 18, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28594170/pharmaceutical-approaches-to-target-antibiotic-resistance-mechanisms
#7
Domenico Schillaci, Virginia Spanò, Barbara Parrino, Anna Carbone, Alessandra Montalbano, Paola Barraja, Patrizia Diana, Girolamo Cirrincione, Stella Cascioferro
There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activation of efflux pumps. Here we assess the current landscape and challenges in the treatment of antibiotic resistance mechanisms at both bacterial cell and community levels. We also discuss the potential clinical application of chemical inhibitors of antibiotic resistance mechanisms as add-on treatments for serious drug-resistant infections...
June 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28590820/activity-of-ceftazidime-avibactam-against-clinical-isolates-of-klebsiella-pneumoniae-including-kpc-carrying-isolates-endemic-to-new-york-city
#8
Nyla Manning, Gregory Balabanian, Michael Rose, David Landman, John Quale
In this report, we examined the (1) activity of ceftazidime-avibactam against clinical isolates Klebsiella pneumoniae, including those harboring blaKPC, (2) potential mechanisms leading to reduced susceptibility, and (3) activity of ceftazidime-avibactam when combined with other agents. Of 802 carbapenem-resistant isolates of K. pneumoniae gathered from New York City from 1999 to 2014, all were susceptible to ceftazidime-avibactam. Minimum inhibitory concentrations (MICs) were higher in isolates with K. pneumoniae, with the carbapenemase (KPC)-3 (compared to KPC-2), and those with a frameshift mutation in ompK35...
June 7, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28559260/an-unusual-e-coli-pbp3-insertion-sequence-identified-from-a-collection-of-carbapenem-resistant-enterobacteriaceae-cre-tested-in-vitro-with-ceftazidime-ceftaroline-or-aztreonam-avibactam-combinations
#9
Yunliang Zhang, Ankita Kashikar, C Adam Brown, Gerald Denys, Karen Bush
Carbapenemase-producing Enterobacteriaceae isolates (n=110) from healthcare centers in central Indiana (2010-2013) were tested for susceptibility to combinations of avibactam (4 μg/ml) with ceftazidime, ceftaroline or aztreonam. MIC50/MIC90 values were 1/2 μg/ml (ceftazidime-avibactam), 0.5/2 μg/ml (ceftaroline-avibactam) and 0.25/0.5 μg/ml (aztreonam-avibactam.) A β-lactam MIC of 8 μg/ml was reported for the three combinations against one Escherichia coli isolate with an unusual TIPY insertion following Tyr344 in penicillin-binding protein 3 (PBP3) as the result of gene duplication...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28559250/ceftazidime-avibactam-is-superior-to-other-treatment-regimens-against-carbapenem-resistant-klebsiella-pneumoniae-bacteremia
#10
Ryan K Shields, M Hong Nguyen, Liang Chen, Ellen G Press, Brian A Potoski, Rachel V Marini, Yohei Doi, Barry N Kreiswirth, Cornelius J Clancy
There are no data comparing outcomes of patients treated with ceftazidime-avibactam vs. comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P=0.006) and survival (P=0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% were KPC-producing)...
May 30, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28505331/antimicrobial-susceptibility-of-clinical-isolates-of-neisseria-gonorrhoeae-to-alternative-antimicrobials-with-therapeutic-potential
#11
P R S Lagacé-Wiens, H J Adam, N M Laing, M R Baxter, I Martin, M R Mulvey, J A Karlowsky, D J Hoban, G G Zhanel
Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N...
May 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28483952/outcomes-with-ceftazidime-avibactam-in-patients-with-carbapenem-resistant-enterobacteriaceae-cre-infections-a-multi-center-study
#12
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 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 whereby 60 patients 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.
May 8, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28461318/impaired-inhibition-by-avibactam-and-resistance-to-the-ceftazidime-avibactam-combination-due-to-the-d-179-y-substitution-in-the-%C3%AE-lactamase-kpc-2
#13
Fabrice Compain, Michel Arthur
The ceftazidime-avibactam combination was recently shown to be at risk of emergence of resistance under treatment. To gain insight into the underlying mechanism, we have analyzed the catalytic properties of a KPC-2 β-lactamase harboring the D(179)Y substitution. We show that impaired inhibition by avibactam combined with significant residual activity for ceftazidime hydrolysis accounts for resistance. In contrast, the D(179)Y substitution abolished hydrolysis of aztreonam and imipenem indicating these drugs might provide therapeutic alternatives...
May 1, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28439137/compatibility-of-ceftazidime-avibactam-ceftolozane-tazobactam-and-piperacillin-tazobactam-with-vancomycin-in-dextrose-5-in-water
#14
Kevin Meyer, Maressa Santarossa, Larry H Danziger, Eric Wenzler
Objectives: The compatibility of vancomycin with existing and novel β-lactam/β-lactamase inhibitors at clinically relevant concentrations in 5% dextrose in water has not been fully explored to date. Methods: Vancomycin concentrations tested ranged from 5 to 20 mg/mL. Ceftazidime-avibactam was tested at 8, 20, and 40 mg/mL, ceftolozane-tazobactam at 15 mg/mL, and piperacillin-tazobactam at 28 mg/mL. Compatibility of drug admixtures were tested via both simulated and actual y-site infusion. For the simulated y-site compatibility assessment, 1:1 mixtures of each respective drug were analyzed over 24 hours...
March 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28416558/in-vitro-discordance-with-in-vivo-activity-humanized-exposures-of-ceftazidime-avibactam-aztreonam-and-tigecycline-alone-and-in-combination-against-new-delhi-metallo-%C3%AE-lactamase-producing-klebsiella-pneumoniae-in-a-murine-lung-infection-model
#15
M L Monogue, L M Abbo, R Rosa, J F Camargo, O Martinez, R A Bonomo, D P Nicolau
The management of infections with New Delhi Metallo-beta-lactamase-1 (NDM) producing bacteria remains clinically challenging given the multi-drug resistant (MDR) phenotype associated with these bacteria. Despite resistance in vitro, ceftazidime-avibactam previously demonstrated in vivo activity against NDM+ Enterobacteriaceae. Herein, we observed in vitro synergy with ceftazidime-avibactam and aztreonam against a MDR K. pneumoniae harboring NDM. In vivo, humanized doses of ceftazidime-avibactam monotherapy resulted in > 2 log10CFU bacterial reduction, therefore, no in vivo synergy was observed...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416553/pharmacokinetics-and-dialytic-clearance-of-ceftazidime-avibactam-in-a-critically-ill-patient-on-continuous-venovenous-hemofiltration
#16
Eric Wenzler, Kristen L Bunnell, Susan C Bleasdale, Scott Benken, Larry H Danziger, Keith A Rodvold
Ceftazidime-avibactam 1.25 g every 8 hours was used to treat multi-drug resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Pre-filter plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 hours along with post-filter and ultrafiltrate concentrations at hours 2 and 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were Cmax 61.10 and 14.54 mg/L, Cmin 31.96 and 8.45 mg/L, t1/2 6...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28396547/resistance-to-ceftazidime-avibactam-in-klebsiella-pneumoniae-due-to-porin-mutations-and-the-increased-expression-of-kpc-3
#17
Romney M Humphries, Peera Hemarajata
We reported the first clinical case of a ceftazidime-avibactam resistant KPC-3-producing Klebsiella pneumoniae (1), from a patient with no prior history of ceftazidime-avibactam therapy.….
April 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28392315/clinical-efficacy-of-ceftazidime-avibactam-versus-other-active-agents-for-the-treatment-of-bacteremia-due-to-carbapenemase-producing-enterobacteriaceae-in-hematologic-patients
#18
Juan J Castón, Isabel Lacort-Peralta, Pilar Martín-Dávila, Belén Loeches, Salvador Tabares, Liz Temkin, Julián Torre-Cisneros, José R Paño-Pardo
OBJECTIVES: The primary objective was to describe clinical features, treatment and outcomes in patients with carbapenemase-producing Enterobacteriaceae (CPE) bacteremia. Additionally, patients treated with ceftazidime/avibactam (study group) were compared to the rest of the patients (comparator group) to determine the influence of the treatment in both crude mortality and clinical cure. METHODS: Multicenter and retrospective study that included patients with hematologic malignancies who had CPE bacteremia...
April 6, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28389354/treating-complicated-carbapenem-resistant-enterobacteriaceae-infections-with-ceftazidime-avibactam-a-retrospective-study-with-molecular-strain-characterisation
#19
Fiorella Krapp, Jennifer L Grant, Sarah H Sutton, Egon A Ozer, Viktorija O Barr
Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI...
June 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28374117/virtual-screening-for-potential-inhibitors-of-ctx-m-15-protein-of-klebsiella-pneumoniae
#20
Tayebeh Farhadi, Atefeh Fakharian, Roman S Ovchinnikov
The Gram-negative bacterium Klebsiella pneumoniae, responsible for a wide variety of nosocomial infections in immuno-deficient patients, involves the respiratory, urinary and gastrointestinal tract infections and septicemia. Extended spectrum β-lactamases (ESBL) belong to β-lactamases capable of conferring antibiotic resistance in Gram-negative bacteria. CTX-M-15, a prevalent ESBL reported from Enterobacteriaceae including K. pneumoniae, was selected as a potent anti-bacterial target. To identify the novel drug-like compounds, structure-based screening procedure was employed against downloaded drug-like compounds from ZINC database...
April 3, 2017: Interdisciplinary Sciences, Computational Life Sciences
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