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Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program

In vitro activities of ceftazidime-avibactam (CAZ-AVI) and key comparators against AmpC-overproducing Enterobacterales and Pseudomonas aeruginosa isolates from four Phase 3 clinical trials and against OXA-48–producing Enterobacterales with multiple resistance mechanisms from the Antimicrobial Testin...

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Autores principales: Lin, Lynn-Yao, Debabov, Dmitri, Chang, William, Stone, Gregory, Riccobene, Todd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923174/
https://www.ncbi.nlm.nih.gov/pubmed/35225651
http://dx.doi.org/10.1128/aac.01985-21
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author Lin, Lynn-Yao
Debabov, Dmitri
Chang, William
Stone, Gregory
Riccobene, Todd
author_facet Lin, Lynn-Yao
Debabov, Dmitri
Chang, William
Stone, Gregory
Riccobene, Todd
author_sort Lin, Lynn-Yao
collection PubMed
description In vitro activities of ceftazidime-avibactam (CAZ-AVI) and key comparators against AmpC-overproducing Enterobacterales and Pseudomonas aeruginosa isolates from four Phase 3 clinical trials and against OXA-48–producing Enterobacterales with multiple resistance mechanisms from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program were evaluated. Susceptibility to CAZ-AVI and comparators was determined by reference broth microdilution methods. Clinical response at test of cure (TOC) was assessed in patients from Phase 3 trials with baseline OXA-48–producing Enterobacterales or AmpC-overproducing Enterobacterales and P. aeruginosa treated with CAZ-AVI or comparators. Against 77 AmpC-overproducing Enterobacterales isolates from Phase 3 trials, meropenem-vaborbactam (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (96.1% S) had similar in vitro activity and were more active than ceftolozane-tazobactam (24.7% S). Clinical cure rates in patients with baseline AmpC-overproducing Enterobacterales were 80.7% (n = 21/26) and 85.0% (n = 17/20) for CAZ-AVI and comparators. Against 53 AmpC-overproducing P. aeruginosa isolates from Phase 3 trials, CAZ-AVI (73.6% S) was more active in vitro than ceftolozane-tazobactam (58.5% S) and meropenem (37.7% S). Clinical cure rates in patients with baseline AmpC-overproducing P. aeruginosa were 85.7% (n = 12/14) and 75.0% (n = 9/12) for CAZ-AVI and comparators, respectively. Of 113 OXA-48–producing isolates from the ATLAS program, 99.1% were susceptible to CAZ-AVI. Four patients with baseline OXA-48–producing Klebsiella pneumoniae isolates treated with CAZ-AVI in Phase 3 trials were clinical cures at TOC and had favorable microbiological response. CAZ-AVI was among the most active agents against AmpC-overproducing P. aeruginosa and Enterobacterales and had greater in vitro activity against OXA-48–producing Enterobacterales than meropenem-vaborbactam, meropenem, ceftolozane-tazobactam, and other comparators.
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spelling pubmed-89231742022-03-16 Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program Lin, Lynn-Yao Debabov, Dmitri Chang, William Stone, Gregory Riccobene, Todd Antimicrob Agents Chemother Epidemiology and Surveillance In vitro activities of ceftazidime-avibactam (CAZ-AVI) and key comparators against AmpC-overproducing Enterobacterales and Pseudomonas aeruginosa isolates from four Phase 3 clinical trials and against OXA-48–producing Enterobacterales with multiple resistance mechanisms from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program were evaluated. Susceptibility to CAZ-AVI and comparators was determined by reference broth microdilution methods. Clinical response at test of cure (TOC) was assessed in patients from Phase 3 trials with baseline OXA-48–producing Enterobacterales or AmpC-overproducing Enterobacterales and P. aeruginosa treated with CAZ-AVI or comparators. Against 77 AmpC-overproducing Enterobacterales isolates from Phase 3 trials, meropenem-vaborbactam (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (96.1% S) had similar in vitro activity and were more active than ceftolozane-tazobactam (24.7% S). Clinical cure rates in patients with baseline AmpC-overproducing Enterobacterales were 80.7% (n = 21/26) and 85.0% (n = 17/20) for CAZ-AVI and comparators. Against 53 AmpC-overproducing P. aeruginosa isolates from Phase 3 trials, CAZ-AVI (73.6% S) was more active in vitro than ceftolozane-tazobactam (58.5% S) and meropenem (37.7% S). Clinical cure rates in patients with baseline AmpC-overproducing P. aeruginosa were 85.7% (n = 12/14) and 75.0% (n = 9/12) for CAZ-AVI and comparators, respectively. Of 113 OXA-48–producing isolates from the ATLAS program, 99.1% were susceptible to CAZ-AVI. Four patients with baseline OXA-48–producing Klebsiella pneumoniae isolates treated with CAZ-AVI in Phase 3 trials were clinical cures at TOC and had favorable microbiological response. CAZ-AVI was among the most active agents against AmpC-overproducing P. aeruginosa and Enterobacterales and had greater in vitro activity against OXA-48–producing Enterobacterales than meropenem-vaborbactam, meropenem, ceftolozane-tazobactam, and other comparators. American Society for Microbiology 2022-03-15 /pmc/articles/PMC8923174/ /pubmed/35225651 http://dx.doi.org/10.1128/aac.01985-21 Text en Copyright © 2022 Lin et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Epidemiology and Surveillance
Lin, Lynn-Yao
Debabov, Dmitri
Chang, William
Stone, Gregory
Riccobene, Todd
Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title_full Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title_fullStr Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title_full_unstemmed Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title_short Antimicrobial Activity of Ceftazidime-Avibactam and Comparators against Pathogens Harboring OXA-48 and AmpC Alone or in Combination with Other β-Lactamases Collected from Phase 3 Clinical Trials and an International Surveillance Program
title_sort antimicrobial activity of ceftazidime-avibactam and comparators against pathogens harboring oxa-48 and ampc alone or in combination with other β-lactamases collected from phase 3 clinical trials and an international surveillance program
topic Epidemiology and Surveillance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923174/
https://www.ncbi.nlm.nih.gov/pubmed/35225651
http://dx.doi.org/10.1128/aac.01985-21
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