Cargando…
2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study
BACKGROUND: Multidrug resistant (MDR) Gram-negative bacteria, including metallo-β-lactamase (MBL) producers, pose significant treatment challenges. This study investigated efficacy and safety of aztreonam-avibactam (ATM-AVI) in the treatment of complicated intra-abdominal infection (cIAI) or hospita...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676936/ http://dx.doi.org/10.1093/ofid/ofad500.2476 |
_version_ | 1785150011508523008 |
---|---|
author | Carmeli, Yehuda Cisneros, Jose-Miguel Paul, Mical Daikos, Georgios L Wang, Minggui Cisneros, Julian Torre Singer, George Titov, Ivan Gumenchuk, Illia Zhao, Yongjie Jiménez Rodríguez, Rosa-María Liang, Lu Chen, Gang Pyptiuk, Oleksandr Aksoy, Firdevs Rogers, Halley Wible, Michele Arhin, Francis Luckey, Alison Leaney, Joanne Pypstra, Rienk Chow, Joseph |
author_facet | Carmeli, Yehuda Cisneros, Jose-Miguel Paul, Mical Daikos, Georgios L Wang, Minggui Cisneros, Julian Torre Singer, George Titov, Ivan Gumenchuk, Illia Zhao, Yongjie Jiménez Rodríguez, Rosa-María Liang, Lu Chen, Gang Pyptiuk, Oleksandr Aksoy, Firdevs Rogers, Halley Wible, Michele Arhin, Francis Luckey, Alison Leaney, Joanne Pypstra, Rienk Chow, Joseph |
author_sort | Carmeli, Yehuda |
collection | PubMed |
description | BACKGROUND: Multidrug resistant (MDR) Gram-negative bacteria, including metallo-β-lactamase (MBL) producers, pose significant treatment challenges. This study investigated efficacy and safety of aztreonam-avibactam (ATM-AVI) in the treatment of complicated intra-abdominal infection (cIAI) or hospital-acquired)/ventilator-associated pneumonia (HAP/VAP) due to Gram-negative bacteria, including MBL-producing MDR pathogens, with limited or no treatment options. METHODS: REVISIT was a phase 3, prospective, randomized, multicenter, open-label, central assessor-blinded study in hospitalized adults. Patients were randomized 2:1 to ATM-AVI (± metronidazole [MTZ]; cIAI patients only) or meropenem (MER) ± colistin (COL) for 5–14 (cIAI) or 7–14 (HAP/VAP) days. Clinical cure at the test-of-cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) analysis sets were the primary efficacy endpoints. Key secondary endpoints included microbiological responses at TOC, 28-day mortality, and safety. No formal hypothesis testing was planned. RESULTS: In total, 422 patients were randomized (ATM-AVI ± MTZ, n=282; MER ± COL, n=140). Adjudicated clinical cure rates at TOC are shown in Table 1. Favorable microbiological response rates at TOC (micro-ITT analysis set) were 75.7% for ATM-AVI ± MTZ and 73.9% for MER ± COL; 28-day all-cause mortality rates for ATM-AVI ± MTZ and MER ± COL were 1.9% (4/208) vs 2.9% (3/104), and 10.8% (8/74) vs 19.4% (7/36) in cIAI and HAP/VAP, respectively. Adverse events (AEs) are summarized in Table 2. There were no treatment-related serious AEs in the ATM-AVI group. [Figure: see text] [Figure: see text] CONCLUSION: ATM-AVI (± MTZ) was effective in treating patients with cIAI and HAP/VAP, displaying similar efficacy to MER ± COL. ATM-AVI was generally well tolerated. These data support potential use of ATM-AVI for the treatment of serious infections caused by susceptible Gram-negative bacteria. Further analyses will focus on MBL-producing pathogens. Trial registration. NCT03329092. Study sponsored by Pfizer. ATM-AVI is jointly developed with AbbVie, also supported by the United States Biomedical Advanced Research and Development Authority (BARDA) and the European Innovative Medicines Initiative (IMI), under the COMBACTE-CARE consortium. DISCLOSURES: Yehuda Carmeli, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Qpex: Advisor/Consultant|Qpex: Grant/Research Support|Qpex: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|Roche: Honoraria Georgios L. Daikos, PhD, MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Viatris: Honoraria Rosa-María Jiménez Rodríguez, MD, PhD, Abex: Honoraria|B. Braun: Honoraria|Johnson & Johnson: Honoraria Halley Rogers, MPH, Pfizer: Ownership Interest Michele Wible, MS, Pfizer: Ownership Interest Francis Arhin, PhD, Pfizer: Ownership Interest Joanne Leaney, PhD, Pfizer: Ownership Interest Rienk Pypstra, MD, MBA, Pfizer: Stocks/Bonds Joseph Chow, MD, Pfizer: Ownership Interest |
format | Online Article Text |
id | pubmed-10676936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-106769362023-11-27 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study Carmeli, Yehuda Cisneros, Jose-Miguel Paul, Mical Daikos, Georgios L Wang, Minggui Cisneros, Julian Torre Singer, George Titov, Ivan Gumenchuk, Illia Zhao, Yongjie Jiménez Rodríguez, Rosa-María Liang, Lu Chen, Gang Pyptiuk, Oleksandr Aksoy, Firdevs Rogers, Halley Wible, Michele Arhin, Francis Luckey, Alison Leaney, Joanne Pypstra, Rienk Chow, Joseph Open Forum Infect Dis Abstract BACKGROUND: Multidrug resistant (MDR) Gram-negative bacteria, including metallo-β-lactamase (MBL) producers, pose significant treatment challenges. This study investigated efficacy and safety of aztreonam-avibactam (ATM-AVI) in the treatment of complicated intra-abdominal infection (cIAI) or hospital-acquired)/ventilator-associated pneumonia (HAP/VAP) due to Gram-negative bacteria, including MBL-producing MDR pathogens, with limited or no treatment options. METHODS: REVISIT was a phase 3, prospective, randomized, multicenter, open-label, central assessor-blinded study in hospitalized adults. Patients were randomized 2:1 to ATM-AVI (± metronidazole [MTZ]; cIAI patients only) or meropenem (MER) ± colistin (COL) for 5–14 (cIAI) or 7–14 (HAP/VAP) days. Clinical cure at the test-of-cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) analysis sets were the primary efficacy endpoints. Key secondary endpoints included microbiological responses at TOC, 28-day mortality, and safety. No formal hypothesis testing was planned. RESULTS: In total, 422 patients were randomized (ATM-AVI ± MTZ, n=282; MER ± COL, n=140). Adjudicated clinical cure rates at TOC are shown in Table 1. Favorable microbiological response rates at TOC (micro-ITT analysis set) were 75.7% for ATM-AVI ± MTZ and 73.9% for MER ± COL; 28-day all-cause mortality rates for ATM-AVI ± MTZ and MER ± COL were 1.9% (4/208) vs 2.9% (3/104), and 10.8% (8/74) vs 19.4% (7/36) in cIAI and HAP/VAP, respectively. Adverse events (AEs) are summarized in Table 2. There were no treatment-related serious AEs in the ATM-AVI group. [Figure: see text] [Figure: see text] CONCLUSION: ATM-AVI (± MTZ) was effective in treating patients with cIAI and HAP/VAP, displaying similar efficacy to MER ± COL. ATM-AVI was generally well tolerated. These data support potential use of ATM-AVI for the treatment of serious infections caused by susceptible Gram-negative bacteria. Further analyses will focus on MBL-producing pathogens. Trial registration. NCT03329092. Study sponsored by Pfizer. ATM-AVI is jointly developed with AbbVie, also supported by the United States Biomedical Advanced Research and Development Authority (BARDA) and the European Innovative Medicines Initiative (IMI), under the COMBACTE-CARE consortium. DISCLOSURES: Yehuda Carmeli, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Qpex: Advisor/Consultant|Qpex: Grant/Research Support|Qpex: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support|Roche: Honoraria Georgios L. Daikos, PhD, MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Viatris: Honoraria Rosa-María Jiménez Rodríguez, MD, PhD, Abex: Honoraria|B. Braun: Honoraria|Johnson & Johnson: Honoraria Halley Rogers, MPH, Pfizer: Ownership Interest Michele Wible, MS, Pfizer: Ownership Interest Francis Arhin, PhD, Pfizer: Ownership Interest Joanne Leaney, PhD, Pfizer: Ownership Interest Rienk Pypstra, MD, MBA, Pfizer: Stocks/Bonds Joseph Chow, MD, Pfizer: Ownership Interest Oxford University Press 2023-11-27 /pmc/articles/PMC10676936/ http://dx.doi.org/10.1093/ofid/ofad500.2476 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstract Carmeli, Yehuda Cisneros, Jose-Miguel Paul, Mical Daikos, Georgios L Wang, Minggui Cisneros, Julian Torre Singer, George Titov, Ivan Gumenchuk, Illia Zhao, Yongjie Jiménez Rodríguez, Rosa-María Liang, Lu Chen, Gang Pyptiuk, Oleksandr Aksoy, Firdevs Rogers, Halley Wible, Michele Arhin, Francis Luckey, Alison Leaney, Joanne Pypstra, Rienk Chow, Joseph 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title | 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title_full | 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title_fullStr | 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title_full_unstemmed | 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title_short | 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study |
title_sort | 2893 a. efficacy and safety of aztreonam-avibactam for the treatment of serious infections due to gram-negative bacteria, including metallo-β-lactamase-producing pathogens: phase 3 revisit study |
topic | Abstract |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676936/ http://dx.doi.org/10.1093/ofid/ofad500.2476 |
work_keys_str_mv | AT carmeliyehuda 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT cisnerosjosemiguel 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT paulmical 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT daikosgeorgiosl 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT wangminggui 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT cisnerosjuliantorre 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT singergeorge 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT titovivan 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT gumenchukillia 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT zhaoyongjie 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT jimenezrodriguezrosamaria 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT lianglu 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT chengang 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT pyptiukoleksandr 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT aksoyfirdevs 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT rogershalley 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT wiblemichele 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT arhinfrancis 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT luckeyalison 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT leaneyjoanne 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT pypstrarienk 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy AT chowjoseph 2893aefficacyandsafetyofaztreonamavibactamforthetreatmentofseriousinfectionsduetogramnegativebacteriaincludingmetalloblactamaseproducingpathogensphase3revisitstudy |