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...
| Autores: | , , , , , , |
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| Tipo de documento: | artigo |
| Estado: | Versão publicada |
| Data de publicação: | 2025 |
| País: | España |
| Recursos: | Universidad de Sevilla (US) |
| Repositório: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/176884 |
| Acesso em linha: | https://hdl.handle.net/11441/176884 https://doi.org/10.1093/jacamr/dlaf131 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Aztreonam-avibactam Infections Metallo-β-lactamase Gram-negative pathogens |
| Resumo: | 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 [microbio logical ITT (micro-ITT) analysis set]. Secondary endpoints included microbiological response at TOC, 28-day mor tality 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 [az treonam–avibactam, 6/12 (50%); BAT, 2/3 (67%)]. MBL subtypes/variants identified in the aztreonam–avibac tam 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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