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https://www.readbyqxmd.com/read/28815897/multidrug-resistant-enterobacteriaceae-pseudomonas-aeruginosa-and-vancomycin-resistant-enterococci-three-major-threats-to-hematopoietic-stem-cell-transplant-recipients
#1
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
#2
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/28807908/activity-of-the-%C3%AE-lactamase-inhibitor-ln-1-255-against-carbapenem-hydrolyzing-class-d-%C3%AE-lactamases-from-acinetobacter-baumannii
#3
Juan Carlos Vázquez-Ucha, María Maneiro, Marta Martínez-Guitián, John Buynak, Christopher R Bethel, Robert A Bonomo, Germán Bou, Margarita Poza, Concepción González-Bello, Alejandro Beceiro
The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in A. baumannii, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant A. baumannii strains constitutes a serious global threat. Carbapenems have been successfully utilized as last resort antibiotics for the treatment of multi-drug-resistant A...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28803496/management-of-multidrug-resistant-pseudomonas-aeruginosa-in-the-intensive-care-unit-state-of-the-art
#4
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 14, 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
#5
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
#6
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
#7
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
#8
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/28739781/structural-insights-into-the-tla-3-extended-spectrum-%C3%AE-lactamase-and-its-inhibition-by-avibactam-and-op0595
#9
Wanchun Jin, Jun-Ichi Wachino, Yoshihiro Yamaguchi, Kouji Kimura, Anupriya Kumar, Mototsugu Yamada, Akihiro Morinaka, Yoshiaki Sakamaki, Minoru Yonezawa, Hiromasa Kurosaki, Yoshichika Arakawa
Development of effective inhibitors that block extended-spectrum β-lactamases (ESBLs) and restore the action of β-lactams represents an effective strategy against ESBL-producing Enterobacteriaceae We evaluated the inhibitory effect of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent Ki app of 1.71 ± 0.10 and 1.49 ± 0.05 μM, respectively, and could restore susceptibility to cephalosporins in TLA-3-producing Escherichia coli The acylation rate constant [k2/K, (3...
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
#10
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/28738449/pbpk-modeling-of-the-effect-of-reduced-kidney-function-on-the-pharmacokinetics-of-drugs-excreted-renally-by-organic-anion-transporters
#11
C-H Hsueh, V Hsu, P Zhao, L Zhang, K M Giacomini, S-M Huang
Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs)...
July 24, 2017: Clinical Pharmacology and Therapeutics
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
#12
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/28678295/-13-c-carbamylation-as-a-mechanistic-probe-for-the-inhibition-of-class-d-%C3%AE-lactamases-by-avibactam-and-halide-ions
#13
Christopher T Lohans, David Y Wang, Christian Jorgensen, Samuel T Cahill, Ian J Clifton, Michael A McDonough, Henry P Oswin, James Spencer, Carmen Domene, Timothy D W Claridge, Jürgen Brem, Christopher J Schofield
The class D (OXA) serine β-lactamases are a major cause of resistance to β-lactam antibiotics. The class D enzymes are unique amongst β-lactamases because they have a carbamylated lysine that acts as a general acid/base in catalysis. Previous crystallographic studies led to the proposal that β-lactamase inhibitor avibactam targets OXA enzymes in part by promoting decarbamylation. Similarly, halide ions are proposed to inhibit OXA enzymes via decarbamylation. NMR analyses, in which the carbamylated lysines of OXA-10, -23 and -48 were (13)C-labelled, indicate that reaction with avibactam does not ablate lysine carbamylation in solution...
July 19, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28674059/in-vivo-emergence-of-resistance-to-novel-cephalosporin-%C3%AE-lactamase-inhibitor-combinations-through-the-duplication-of-the-amino-acid-d149-from-oxa-2-%C3%AE-lactamase-oxa-539-in-st235-pseudomonas-aeruginosa
#14
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 ST235 and were resistant to carbapenems (oprD-), fluoroquinolones (GyrA-T83I, ParC-S87L) and aminoglycosides (aacA7/aacA8/aadA6). 98G1 additionally 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)...
July 3, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28637339/emergence-of-ceftazidime-avibactam-non-susceptibility-in-an-mdr-klebsiella-pneumoniae-isolate
#15
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
#16
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
#17
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
#18
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
#19
Adnan Alatoom, Hashim Elsayed, Karen Lawlor, Laila AbdelWareth, Rania El-Lababidi, Lysettee Cardona, Mohammad Mooty, Maria-Fernanda Bonilla, Ahmad Nusair, Imran Mirza
OBJECTIVE: This study compared the activity of ceftolozane-tazobactam and ceftazidime-avibactam against 120 bacterial strains, including extended-spectrum beta-lactamase (ESBL) producers, carbapenem-resistant Enterobacteriaceae (CRE), and Pseudomonas aeruginosa, isolated from patients admitted to Cleveland Clinic Abu Dhabi, United Arab Emirates. METHODS: In vitro susceptibility was tested using the Etest strip minimum inhibitory concentration (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
#20
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
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