George L Daikos, José Miguel Cisneros, Yehuda Carmeli, Minggui Wang, Chee Loon Leong, Konstantinos Pontikis, Anastasia Anderzhanova, Simin Florescu, Roman Kozlov, Eduardo Rodriguez-Noriega, Mina Psichogiou, Pinyo Rattanaumpawan, Anca Streinu-Cercel, Venkatasubramanian Ramasubramanian, Francis F Arhin, Halley Rogers, Michele Wible, Joanne Leaney, Daria Jacobson, Rienk Pypstra, Joseph W Chow
{"title":"Aztreonam-avibactam用于治疗由产生金属β-内酰胺酶的革兰氏阴性病原体引起的严重感染：一项3期随机试验（ASSEMBLE）。","authors":"George L Daikos, José Miguel Cisneros, Yehuda Carmeli, Minggui Wang, Chee Loon Leong, Konstantinos Pontikis, Anastasia Anderzhanova, Simin Florescu, Roman Kozlov, Eduardo Rodriguez-Noriega, Mina Psichogiou, Pinyo Rattanaumpawan, Anca Streinu-Cercel, Venkatasubramanian Ramasubramanian, Francis F Arhin, Halley Rogers, Michele Wible, Joanne Leaney, Daria Jacobson, Rienk Pypstra, Joseph W Chow","doi":"10.1093/jacamr/dlaf131","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Phase 3 ASSEMBLE study investigated aztreonam-avibactam versus best available therapy (BAT) for treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) or bloodstream infection (BSI) caused by confirmed MBL-producing multidrug-resistant pathogens.</p><p><strong>Methods: </strong>This prospective, multicentre, randomized, open-label, central assessor-blinded study randomized hospitalized adults 2:1 to aztreonam-avibactam [+ metronidazole (cIAI)] or BAT for 5-14 (cIAI, cUTI and BSI) or 7-14 (HAP/VAP) days. Primary endpoint was clinical cure at test-of-cure (TOC) visit on Day 28 ± 3 [microbiological ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mortality and safety. No formal hypothesis testing was planned.</p><p><strong>Results: </strong>Fifteen patients were randomized [aztreonam-avibactam, <i>n</i> = 12; BAT, <i>n</i> = 3 (ITT and micro-ITT analysis sets)]. Most frequent baseline pathogens were Enterobacterales; <i>Klebsiella pneumoniae</i> was most common [aztreonam-avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam-avibactam group were NDM-1 (<i>n</i> = 7), NDM-5 (<i>n</i> = 3), VIM-2 (<i>n</i> = 2) and L1 (<i>n</i> = 3); and for BAT were NDM-1 (<i>n</i> = 2) and NDM-5 (<i>n</i> = 1). Clinical cure rates at TOC were 5/12 (42%) for aztreonam-avibactam and 0/3 (0%) for BAT. Per-patient microbiological responses were generally consistent with clinical responses. Twenty-eight-day all-cause mortality rates for aztreonam-avibactam and BAT were 1/12 (8%) and 1/3 (33%), respectively. Aztreonam-avibactam was generally well-tolerated, with no treatment-related serious adverse events.</p><p><strong>Conclusions: </strong>These Phase 3 data provide support for aztreonam-avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"7 4","pages":"dlaf131"},"PeriodicalIF":3.3000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301880/pdf/","citationCount":"0","resultStr":"{\"title\":\"Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE).\",\"authors\":\"George L Daikos, José Miguel Cisneros, Yehuda Carmeli, Minggui Wang, Chee Loon Leong, Konstantinos Pontikis, Anastasia Anderzhanova, Simin Florescu, Roman Kozlov, Eduardo Rodriguez-Noriega, Mina Psichogiou, Pinyo Rattanaumpawan, Anca Streinu-Cercel, Venkatasubramanian Ramasubramanian, Francis F Arhin, Halley Rogers, Michele Wible, Joanne Leaney, Daria Jacobson, Rienk Pypstra, Joseph W Chow\",\"doi\":\"10.1093/jacamr/dlaf131\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The Phase 3 ASSEMBLE study investigated aztreonam-avibactam versus best available therapy (BAT) for treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) or bloodstream infection (BSI) caused by confirmed MBL-producing multidrug-resistant pathogens.</p><p><strong>Methods: </strong>This prospective, multicentre, randomized, open-label, central assessor-blinded study randomized hospitalized adults 2:1 to aztreonam-avibactam [+ metronidazole (cIAI)] or BAT for 5-14 (cIAI, cUTI and BSI) or 7-14 (HAP/VAP) days. Primary endpoint was clinical cure at test-of-cure (TOC) visit on Day 28 ± 3 [microbiological ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mortality and safety. No formal hypothesis testing was planned.</p><p><strong>Results: </strong>Fifteen patients were randomized [aztreonam-avibactam, <i>n</i> = 12; BAT, <i>n</i> = 3 (ITT and micro-ITT analysis sets)]. Most frequent baseline pathogens were Enterobacterales; <i>Klebsiella pneumoniae</i> was most common [aztreonam-avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam-avibactam group were NDM-1 (<i>n</i> = 7), NDM-5 (<i>n</i> = 3), VIM-2 (<i>n</i> = 2) and L1 (<i>n</i> = 3); and for BAT were NDM-1 (<i>n</i> = 2) and NDM-5 (<i>n</i> = 1). Clinical cure rates at TOC were 5/12 (42%) for aztreonam-avibactam and 0/3 (0%) for BAT. Per-patient microbiological responses were generally consistent with clinical responses. Twenty-eight-day all-cause mortality rates for aztreonam-avibactam and BAT were 1/12 (8%) and 1/3 (33%), respectively. Aztreonam-avibactam was generally well-tolerated, with no treatment-related serious adverse events.</p><p><strong>Conclusions: </strong>These Phase 3 data provide support for aztreonam-avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria.</p>\",\"PeriodicalId\":14594,\"journal\":{\"name\":\"JAC-Antimicrobial Resistance\",\"volume\":\"7 4\",\"pages\":\"dlaf131\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301880/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAC-Antimicrobial Resistance\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jacamr/dlaf131\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlaf131","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE).
Background: The Phase 3 ASSEMBLE study investigated aztreonam-avibactam versus best available therapy (BAT) for treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) or bloodstream infection (BSI) caused by confirmed MBL-producing multidrug-resistant pathogens.
Methods: This prospective, multicentre, randomized, open-label, central assessor-blinded study randomized hospitalized adults 2:1 to aztreonam-avibactam [+ metronidazole (cIAI)] or BAT for 5-14 (cIAI, cUTI and BSI) or 7-14 (HAP/VAP) days. Primary endpoint was clinical cure at test-of-cure (TOC) visit on Day 28 ± 3 [microbiological ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mortality and safety. No formal hypothesis testing was planned.
Results: Fifteen patients were randomized [aztreonam-avibactam, n = 12; BAT, n = 3 (ITT and micro-ITT analysis sets)]. Most frequent baseline pathogens were Enterobacterales; Klebsiella pneumoniae was most common [aztreonam-avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam-avibactam group were NDM-1 (n = 7), NDM-5 (n = 3), VIM-2 (n = 2) and L1 (n = 3); and for BAT were NDM-1 (n = 2) and NDM-5 (n = 1). Clinical cure rates at TOC were 5/12 (42%) for aztreonam-avibactam and 0/3 (0%) for BAT. Per-patient microbiological responses were generally consistent with clinical responses. Twenty-eight-day all-cause mortality rates for aztreonam-avibactam and BAT were 1/12 (8%) and 1/3 (33%), respectively. Aztreonam-avibactam was generally well-tolerated, with no treatment-related serious adverse events.
Conclusions: These Phase 3 data provide support for aztreonam-avibactam as a potential therapeutic option for difficult-to-treat infections caused by MBL-producing Gram-negative bacteria.
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