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ceftazidime avibactam

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https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#1
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28922808/the-discovery-of-ceftazidime-avibactam-as-an-anti-mycobacterium-avium-agent
#2
Devyani Deshpande, Shashikant Srivastava, Moti L Chapagain, Pooi S Lee, Kayle N Cirrincione, Jotam G Pasipanodya, Tawanda Gumbo
Objectives: To determine if ceftaroline and ceftazidime combined with avibactam are efficacious against pulmonary Mycobacterium avium complex (MAC) disease. Methods: First, we performed a concentration-effect study of ceftaroline and ceftaroline/avibactam against extracellular MAC in test tubes. Given the difficulty of obtaining avibactam at the time of experimentation, we used a single concentration of commercial ceftazidime/avibactam, and two sets of non-treated controls, one with ceftazidime/avibactam and the other without...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28893690/new-agents-for-the-treatment-of-infections-with-gram-negative-bacteria-restoring-the-miracle-or-false-dawn
#3
REVIEW
Hugh Wright, Robert A Bonomo, David L Paterson
BACKGROUND: Antibiotic resistance in gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made. AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or completed advanced clinical trials that possess activity against resistant gram-negative organisms...
September 8, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28882013/antimicrobial-management-in-nosocomial-peritonitis-microbiota-drug-and-time
#4
REVIEW
A Montero, P Salgado Aranda, F Gilsanz, E Maseda
Complicated intra-abdominal infection requires surgical treatment and broad-spectrum empiric antibiotic treatment used early. The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units. The excessive use of carbapenems has led to carbapenemase-producing Enterobacteriaceae, leaving tigecycline and colistin as therapeutical options. The new antimicrobials, ceftazidime-avibactam and ceftolozane-tazobactam open new horizons in the treatment of multi-drug resistant Enterobacteriaceae...
September 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28876489/structural-mechanistic-insights-into-the-efficacy-of-non-classical-%C3%AE-lactamase-inhibitors-against-extensively-drug-resistant-stenotrophomonas-maltophilia-clinical-isolates
#5
Karina Calvopiña, Philip Hinchliffe, Jürgen Brem, Kate J Heesom, Samar Johnson, Ricky Cain, Christopher T Lohans, Colin W G Fishwick, Christopher J Schofield, James Spencer, Matthew B Avison
Clavulanic acid and avibactam are clinically deployed serine β-lactamase inhibitors, important as a defence against antibacterial resistance. Bicyclic boronates are recently discovered inhibitors of serine and some metallo β-lactamases. Here we show that avibactam and a bicyclic boronate inhibit L2 (serine β-lactamase) but not L1 (metallo β-lactamase) from the extensively drug resistant human pathogen Stenotrophomonas maltophilia. X-ray crystallography revealed that both inhibitors bind L2 by covalent attachment to the nucleophilic serine...
September 6, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28875168/ceftazidime-avibactam-has-potent-sterilizing-activity-against-highly-drug-resistant-tuberculosis
#6
Devyani Deshpande, Shashikant Srivastava, Moti Chapagain, Gesham Magombedze, Katherine R Martin, Kayle N Cirrincione, Pooi S Lee, Thearith Koeuth, Keertan Dheda, Tawanda Gumbo
There are currently many patients with multidrug-resistant and extensively drug-resistant tuberculosis. Ongoing transmission of the highly drug-resistant strains and high mortality despite treatment remain problematic. The current strategy of drug discovery and development takes up to a decade to bring a new drug to clinical use. We embarked on a strategy to screen all antibiotics in current use and examined them for use in tuberculosis. We found that ceftazidime-avibactam, which is already used in the clinic for multidrug-resistant Gram-negative bacillary infections, markedly killed rapidly growing, intracellular, and semidormant Mycobacterium tuberculosis in the hollow fiber system model...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28827415/antimicrobial-activity-of-ceftazidime-avibactam-tested-against-multidrug-resistant-enterobacteriaceae-and-pseudomonas-aeruginosa-isolates-from-united-states-medical-centers-2013-2016
#7
Helio S Sader, Mariana Castanheira, Dee Shortridge, Rodrigo E Mendes, Robert K Flamm
The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa. Isolates were consecutively collected from 94 US hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥16 μg/mL) were evaluated for the presence of genes encoding ESBLs, KPC, NDM, and transferable AmpC enzymes...
August 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28815897/multidrug-resistant-enterobacteriaceae-pseudomonas-aeruginosa-and-vancomycin-resistant-enterococci-three-major-threats-to-hematopoietic-stem-cell-transplant-recipients
#8
REVIEW
Michael J Satlin, Thomas J Walsh
Hematopoietic stem cell transplant (HSCT) recipients are uniquely threatened by the emergence of multidrug-resistant (MDR) bacteria because these patients rely on immediate active antimicrobial therapy to combat bacterial infections. This review describes the epidemiology and treatment considerations for three challenging MDR bacterial pathogens in HSCT recipients: MDR Enterobacteriaceae, including extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus (VRE)...
August 16, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28813756/pharmacotherapy-review-of-ceftazidime-avibactam
#9
Amber Yaeger, John Kappes
No abstract text is available yet for this article.
May 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28803496/management-of-multidrug-resistant-pseudomonas-aeruginosa-in-the-intensive-care-unit-state-of-the-art
#10
Alberto Enrico Maraolo, Marco Cascella, Silvia Corcione, Arturo Cuomo, Salvatore Nappa, Guglielmo Borgia, Francesco Giuseppe De Rosa, Ivan Gentile
Pseudomonas aeruginosa (PA) is one of the most important causes of healthcare-related infections among Gram-negative bacteria. The best therapeutic approach is controversial, especially for multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains as well as in the setting of most severe patients, such as in the intensive care unit (ICU). Areas covered: This article addresses several points. First, the main microbiological aspects of PA, focusing on its wide array of resistance mechanisms. Second, risk factors and the worse outcome linked to MDR-PA infection...
August 18, 2017: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/28767588/successful-ceftazidime-avibactam-treatment-of-mdr-kpc-positive-klebsiella-pneumoniae-infection-in-a-patient-with-traumatic-brain-injury-a-case-report
#11
Agnese Gugliandolo, Carla Caio, Maria Lina Mezzatesta, Carmela Rifici, Placido Bramanti, Stefania Stefani, Emanuela Mazzon
RATIONALE: Carbapenem-resistant Enterobacteriaceae infections are a serious health care problem, because of the high mortality. Carbapenem resistance is mainly caused by carbapenemases production, including Klebsiella pneumoniae carbapenemase (KPC). Ceftazidime-avibactam is a new cephalosporin/β-lactamase inhibitor combination for the treatment of complicated urinary, intra-abdominal infections, and nosocomial pneumonia caused by gram negative, or other serious gram-negative infections...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28760708/experimental-design-and-modeling-approach-to-evaluate-efficacy-of-%C3%AE-lactam-%C3%AE-lactamase-inhibitor-combinations
#12
REVIEW
Sherwin K B Sy, Hartmut Derendorf
BACKGROUND: A β-lactamase inhibitor (BLI) confers susceptibility of β-lactamase-expressing multidrug resistant (MDR) organisms to the partnering β-lactam (BL). AIMS: To discuss the experimental design and modeling strategies for 2-drug combination, using ceftazidime- and aztreonam-avibactam combinations, as examples. SOURCES: The information came from several publications on avibactam in vitro time-kill studies and corresponding pharmacodynamic models...
July 28, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28748397/activity-of-the-novel-siderophore-cephalosporin-cefiderocol-against-multidrug-resistant-gram-negative-pathogens
#13
J Dobias, V Dénervaud-Tendon, L Poirel, P Nordmann
The novel siderophore cephalosporin cefiderocol (S-649266) with potent activity against Gram-negative pathogens was recently developed (Shionogi & Co., Ltd.). Here, we evaluated the activity of this new molecule and comparators against a collection of previously characterized Gram-negative isolates using broth microdilution panels. A total of 753 clinical multidrug-resistant Gram-negative isolates collected from hospitals worldwide were tested against cefiderocol and antibiotic comparators (ceftolozane-tazobactam [CT], meropenem [MEM], ceftazidime [CAZ], ceftazidime-avibactam [CZA], colistin [CST], aztreonam [ATM], amikacin [AMK], ciprofloxacin [CIP], cefepime [FEP], and tigecycline [TGC]) for their susceptibility...
July 26, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28739787/resistance-to-ceftazidime-avibactam-is-due-to-transposition-of-kpc-in-a-porin-deficient-strain-of-klebsiella-pneumoniae-with-increased-efflux-activity
#14
Kirk Nelson, Peera Hemarajata, Dongxu Sun, Debora Rubio-Aparicio, Ruslan Tsivkovski, Shangxin Yang, Robert Sebra, Andrew Kasarskis, Hoan Nguyen, Blake M Hanson, Shana Leopold, George Weinstock, Olga Lomovskaya, Romney M Humphries
Ceftazidime-avibactam is an antibiotic with activity against serine beta-lactamases, including KPC. Recently, reports have emerged of KPC-producing isolates resistant to this antibiotic, including a report of a wild-type KPC-3 producing sequence type 258 Klebsiella pneumoniae that was resistant to ceftazidime-avibactam. We describe a detailed analysis of this isolate, in the context of two other closely related KPC-3 producing isolates, recovered from the same patient. Both isolates encoded a non-functional OmpK35, whereas we demonstrate a novel T333N mutation in OmpK36, present in the ceftazidime-avibactam resistant isolate, reduced activity of this porin and impacted ceftazidime-avibactam susceptibility...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28739780/multicenter-evaluation-of-ceftazidime-avibactam-and-ceftolozane-tazobactam-inhibitory-activity-against-meropenem-non-susceptible-p-aeruginosa-from-blood-respiratory-tract-and-wounds
#15
Mordechai Grupper, Christina Sutherland, David P Nicolau
The recent escalation of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of this class of compounds for this prevalent healthcare associate pathogen. Herein, we compared the in-vitro inhibitory activity of ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem non-susceptible Pseudomonas aeruginosa non-duplicate clinical isolates from 34 US hospitals using reference broth microdilution methods. Ceftazidime-avibactam and ceftolozane-tazobactam were active, with ceftolozane-tazobactam having significantly higher inhibitory activity than ceftazidime-avibactam...
July 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28685153/emergence-of-ceftazidime-avibactam-resistance-and-restoration-of-carbapenem-susceptibility-in-klebsiella-pneumoniae-carbapenemase-producing-k-pneumoniae-a-case-report-and-review-of-literature
#16
Ryan K Shields, M Hong Nguyen, Ellen G Press, Liang Chen, Barry N Kreiswirth, Cornelius J Clancy
We used meropenem to successfully treat a patient with bacteremia due to ceftazidime-avibactam-resistant, meropenem- susceptible Klebsiella pneumoniae that carried mutant blaKPC-3. Meropenem was bactericidal against ceftazidime-avibactam- resistant K pneumoniae isolates in vitro. Nevertheless, the role of carbapenems in treating such infections remains uncertain, because meropenem resistance is selected readily during passage experiments.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28674059/in-vivo-emergence-of-resistance-to-novel-cephalosporin-%C3%AE-lactamase-inhibitor-combinations-through-the-duplication-of-amino-acid-d149-from-oxa-2-%C3%AE-lactamase-oxa-539-in-sequence-type-235-pseudomonas-aeruginosa
#17
Pablo A Fraile-Ribot, Xavier Mulet, Gabriel Cabot, Ester Del Barrio-Tofiño, Carlos Juan, José L Pérez, Antonio Oliver
Resistance development to novel cephalosporin-β-lactamase inhibitor combinations during ceftazidime treatment of a surgical infection by Pseudomonas aeruginosa was investigated. Both initial (97C2) and final (98G1) isolates belonged to the high-risk clone sequence type (ST) 235 and were resistant to carbapenems (oprD), fluoroquinolones (GyrA-T83I, ParC-S87L), and aminoglycosides (aacA7/aacA8/aadA6). 98G1 also showed resistance to ceftazidime, ceftazidime-avibactam, and ceftolozane-tazobactam. Sequencing identified blaOXA-2 in 97C2, but 98G1 contained a 3-bp insertion leading to the duplication of the key residue D149 (designated OXA-539)...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#18
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)...
September 1, 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
#19
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 MICs against 100 CRE isolates that underwent whole-genome sequencing. Klebsiella pneumoniae carbapenemases (KPCs) were the most common carbapenemases. Forty-six isolates carried extended-spectrum β-lactamases (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 metallo-β-lactamase (MBL) producers...
September 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
#20
LETTER
Benjamin Davido, Lesly Fellous, Christine Lawrence, Virginie Maxime, Martin Rottman, Aurélien Dinh
No abstract text is available yet for this article.
September 2017: Antimicrobial Agents and Chemotherapy
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