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ceftazidime-avibactam

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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
#1
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
#2
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
#3
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
#4
Juan J Castón, Isabel Lacort, Pilar Martín-Dávila, Belén Loeches, Salvador Tabares, Liz Temkin, Julián Torre-Cisneros, José R Paño
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
#5
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...
April 4, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28369471/activity-of-cefiderocol-s-649266-against-carbapenem-resistant-gram-negative-bacteria-collected-from-inpatients-in-greek-hospitals
#6
Matthew E Falagas, Tilemachos Skalidis, Konstantinos Z Vardakas, Nicholas J Legakis
Background: Cefiderocol (S-649266), a siderophore cephalosporin, utilizes a novel mechanism of entry into the periplasmic space of Gram-negative bacteria and is broadly stable to ESBLs and carbapenemases. Methods: A collection of carbapenem-resistant Gram-negative bacteria isolated from clinical specimens in 18 Greek hospitals was tested for susceptibility to cefiderocol, meropenem, ceftazidime, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam, aztreonam, amikacin, ciprofloxacin, colistin and tigecycline...
March 22, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28363526/a-randomised-double-blind-phase-3-study-comparing-the-efficacy-and-safety-of-ceftazidime-avibactam-plus-metronidazole-versus-meropenem-for-complicated-intra-abdominal-infections-in-hospitalised-adults-in-asia
#7
Xinyu Qin, Binh Giang Tran, Min Ja Kim, Lie Wang, Dung Anh Nguyen, Qian Chen, Jie Song, Peter J Laud, Gregory G Stone, Joseph W Chow
Ceftazidime/avibactam comprises the broad-spectrum cephalosporin ceftazidime and the non-β-lactam β-lactamase inhibitor avibactam. This phase 3, randomised, double-blind study (NCT01726023) assessed the efficacy and safety of ceftazidime/avibactam plus metronidazole compared with meropenem in patients with complicated intra-abdominal infection (cIAI) in Asian countries. Subjects aged 18-90 years and hospitalised with cIAI requiring surgical intervention were randomised 1:1 to receive every 8 h either: ceftazidime/avibactam (2000/500 mg, 2-h infusion) followed by metronidazole (500 mg, 60-min infusion); or meropenem (1000 mg, 30-min infusion)...
March 29, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28362938/the-use-of-noncarbapenem-%C3%AE-lactams-for-the-treatment-of-extended-spectrum-%C3%AE-lactamase-infections
#8
Pranita D Tamma, Jesus Rodriguez-Bano
The continued rise in infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is recognized globally as one of the most pressing concerns facing the healthcare community. Carbapenems are widely regarded as the antibiotics of choice for the treatment of ESBL-producing infections, even when in vitro activity to other β-lactams has been demonstrated. However, indiscriminant carbapenem use is not without consequence, and carbapenem overuse has contributed to the emergence of carbapenem-resistant Enterobacteriaceae...
April 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28348155/molecular-%C3%AE-lactamase-characterization-of-aerobic-gram-negative-pathogens-recovered-from-patients-enrolled-in-the-ceftazidime-avibactam-phase-3-trials-for-complicated-intra-abdominal-infections-efficacies-analyzed-against-susceptible-and-resistant-subsets
#9
Rodrigo E Mendes, Mariana Castanheira, Leah N Woosley, Gregory G Stone, Patricia A Bradford, Robert K Flamm
The correlation of clinical efficacy of ceftazidime-avibactam (plus metronidazole) and meropenem was evaluated in subjects infected with Gram-negative isolates having characterized β-lactam resistance mechanisms from the complicated intra-abdominal infection (cIAI) phase 3 clinical trials. Enterobacteriaceae displaying ceftriaxone and/or ceftazidime MIC values of ≥2 μg/ml and Pseudomonas aeruginosa with ceftazidime MIC values of ≥16 μg/ml were characterized for extended-spectrum β-lactamase (ESBL) content...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28338347/ceftazidime-avibactam-novel-antimicrobial-combination-for-the-treatment-of-complicated-urinary-tract-infections
#10
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/28333323/high-ceftazidime-hydrolysis-activity-and-porin-ompk35-deficiency-contribute-to-the-decreased-susceptibility-to-ceftazidime-avibactam-in-kpc-producing-klebsiella-pneumoniae
#11
Zhen Shen, Baixing Ding, Meiping Ye, Peng Wang, Yingmin Bi, Shi Wu, Xiaogang Xu, Qinglan Guo, Minggui Wang
Objectives: To investigate mechanisms for the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae (KPC-KP). Methods: A total of 24 isolates, 8 each with ceftazidime/avibactam MICs of 4-8, 1-2 and ≤0.5 mg/L, were randomly selected from 214 clinical isolates of KPC-KP, and the β-lactamase hydrolysis activity and porin expression profiles were determined. Plasmid profile and relative expression and copy number of the bla KPC gene were also analysed...
March 15, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28314920/-new-antibiotics-standstill-or-progress
#12
J Rademacher, T Welte
The development of resistance to antibiotics has been ignored for a long time. But nowadays, increasing resistance is an important topic. For a decade no new antibiotics had been developed and it is not possible to quickly close this gap of new resistance and no new drugs. This work presents six new antibiotics (ceftaroline, ceftobiprole, solithromycin, tedizolid, ceftolozane/tazobactam, ceftazidime/avibactam). In part, only expert opinions are given due to lack of study results.The two 5th generation cephalosporins ceftaroline and ceftobiprole have beside their equivalent efficacy to ceftriaxone (ceftaroline) and cefipim (ceftobiprole) high activity against MRSA...
March 17, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28264560/overcoming-an-extremely-drug-resistant-xdr-pathogen-avibactam-restores-susceptibility-to-ceftazidime-for-burkholderia-cepacia-complex-isolates-from-cystic-fibrosis-patients
#13
Krisztina M Papp-Wallace, Scott A Becka, Elise T Zeiser, Nozomi Ohuchi, Maria F Mojica, Julian A Gatta, Monica Falleni, Delfina Tosi, Elisa Borghi, Marisa L Winkler, Brigid M Wilson, John J LiPuma, Michiyoshi Nukaga, Robert A Bonomo
Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different antibiotic classes were unable to inhibit growth. However, all isolates were found to be susceptible to ceftazidime when combined with the novel non-β-lactam β-lactamase inhibitor, avibactam (all minimum inhibitor concentrations (MICs) were ≤8 mg/L of ceftazidime and 4 mg/L of avibactam)...
March 30, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28242667/in-vitro-selection-of-meropenem-resistance-among-ceftazidime-avibactam-resistant-meropenem-susceptible-klebsiella-pneumoniae-isolates-with-variant-kpc-3-carbapenemases
#14
Ryan K Shields, M Hong Nguyen, Ellen G Press, Liang Chen, Barry N Kreiswirth, Cornelius J Clancy
Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected blaKPC-3 mutant (n=5) and wild-type (n=2) K. pneumoniae isolates to serial meropenem passage. Meropenem MICs against all isolates increased. Ompk36 porin mutations evolved in 5 isolates, including those with wild-type blaKPC-3 In different passage lineages, blaKPC-3 mutations reverted to wild-type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam resistant K...
February 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223379/mutations-in-blakpc-3-that-confer-ceftazidime-avibactam-resistance-encode-novel-kpc-3-variants-that-function-as-extended-spectrum-%C3%AE-lactamases
#15
Ghady Haidar, Cornelius J Clancy, Ryan K Shields, Binghua Hao, Shaoji Cheng, M Hong Nguyen
We identified four blaKPC-3 mutations in ceftazidime-avibactam resistant clinical Klebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into Escherichia coli, we conclusively demonstrated that mutant blaKPC-3 encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam MICs, and decreased MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167547/multicenter-clinical-and-molecular-epidemiological-analysis-of-bacteremia-due-to-carbapenem-resistant-enterobacteriaceae-cre-in-the-cre-epicenter-of-the-united-states
#16
Michael J Satlin, Liang Chen, Gopi Patel, Angela Gomez-Simmonds, Gregory Weston, Angela C Kim, Susan K Seo, Marnie E Rosenthal, Steven J Sperber, Stephen G Jenkins, Camille L Hamula, Anne-Catrin Uhlemann, Michael H Levi, Bettina C Fries, Yi-Wei Tang, Stefan Juretschko, Albert D Rojtman, Tao Hong, Barun Mathema, Michael R Jacobs, Thomas J Walsh, Robert A Bonomo, Barry N Kreiswirth
Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28167541/can-ceftazidime-avibactam-and-aztreonam-overcome-%C3%AE-lactam-resistance-conferred-by-metallo-%C3%AE-lactamases-in-enterobacteriaceae
#17
Steven Marshall, Andrea M Hujer, Laura J Rojas, Krisztina M Papp-Wallace, Romney M Humphries, Brad Spellberg, Kristine M Hujer, Emma K Marshall, Susan D Rudin, Federico Perez, Brigid M Wilson, Ronald B Wasserman, Linda Chikowski, David L Paterson, Alejandro J Vila, David van Duin, Barry N Kreiswirth, Henry F Chambers, Vance G Fowler, Michael R Jacobs, Mark E Pulse, William J Weiss, Robert A Bonomo
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof...
April 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28137941/pharmacodynamics-of-ceftazidime-avibactam-against-extracellular-and-intracellular-forms-of-pseudomonas-aeruginosa
#18
J M Buyck, C Luyckx, G G Muccioli, K M Krause, W W Nichols, P M Tulkens, F Van Bambeke
OBJECTIVES: When tested in broth, avibactam reverses ceftazidime resistance in many Pseudomonas aeruginosa that express ESBLs. We examined whether similar reversal is observed against intracellular forms of P. aeruginosa METHODS: Strains: reference strains; two engineered strains with basal non-inducible expression of AmpC and their isogenic mutants with stably derepressed AmpC; and clinical isolates with complete, partial or no resistance to reversion with avibactam. Pharmacodynamic model: 24 h concentration-response to ceftazidime [0...
January 30, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28134677/are-there-any-reasons-to-change-our-behavior-in-necrotizing-fasciitis-with-the-advent-of-new-antibiotics
#19
Francesco Menichetti, Simone Giuliano, Simona Fortunato
PURPOSE OF REVIEW: The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. RECENT FINDINGS: Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable...
April 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28115350/antimicrobial-activities-of-ceftazidime-avibactam-and-comparator-agents-against-clinical-bacteria-isolated-from-patients-with-cancer
#20
Ray Hachem, Ruth Reitzel, Kenneth Rolston, Anne-Marie Chaftari, Issam Raad
A total of 521 unique clinical isolates from cancer patients with primarily (>90%) bloodstream infections were tested for susceptibility to ceftazidime-avibactam and comparators using broth microdilution methods. Ceftazidime-avibactam inhibited 97.8% of all Enterobacteriaceae (n = 321) at the susceptibility breakpoint of ≤8/4 μg/ml (there were 7 nonsusceptible strains). It was also active against Pseudomonas aeruginosa (91.7% isolates susceptible, n = 121), including many isolates not susceptible to meropenem, cefepime, ceftazidime, piperacillin-tazobactam, or other comparators...
April 2017: Antimicrobial Agents and Chemotherapy
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