Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE)
6
Issued Date
2025-08-01
Resource Type
eISSN
26321823
Scopus ID
2-s2.0-105011867129
Journal Title
Jac Antimicrobial Resistance
Volume
7
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Jac Antimicrobial Resistance Vol.7 No.4 (2025)
Suggested Citation
Daikos G.L., Cisneros J.M., Carmeli Y., Wang M., Leong C.L., Pontikis K., Anderzhanova A., Florescu S., Kozlov R., Rodriguez-Noriega E., Psichogiou M., Rattanaumpawan P., Streinu-Cercel A., Ramasubramanian V., Arhin F.F., Rogers H., Wible M., Leaney J., Jacobson D., Pypstra R., Chow J.W. Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE). Jac Antimicrobial Resistance Vol.7 No.4 (2025). doi:10.1093/jacamr/dlaf131 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111539
Title
Aztreonam-avibactam for the treatment of serious infections caused by metallo-β-lactamase-producing Gram-negative pathogens: a Phase 3 randomized trial (ASSEMBLE)
Author's Affiliation
Fudan University
National and Kapodistrian University of Athens
Pfizer Inc.
Universitatea de Medicina si Farmacie Carol Davila din Bucuresti
Tel Aviv Sourasky Medical Center
Hospital Universitario Virgen del Rocío
Siriraj Hospital
Pfizer Limited, UK
Kuala Lumpur Hospital
KAT Hospital
Hospital Civil de Guadalajara
Victor Babes National Institute
Apollo Hospitals Group
Smolensk State Medical Academy
Chest Diseases Hospital 'Sotiria'
Institutul Naţional de Boli Infecţioase „Prof. Dr. Matei Balş“
National Health Commission of the People's Republic of China
Pfizer Inc.
SBHI of the City of Moscow 'N.I.Pirogov City Clinical Hospital #1'
National and Kapodistrian University of Athens
Pfizer Inc.
Universitatea de Medicina si Farmacie Carol Davila din Bucuresti
Tel Aviv Sourasky Medical Center
Hospital Universitario Virgen del Rocío
Siriraj Hospital
Pfizer Limited, UK
Kuala Lumpur Hospital
KAT Hospital
Hospital Civil de Guadalajara
Victor Babes National Institute
Apollo Hospitals Group
Smolensk State Medical Academy
Chest Diseases Hospital 'Sotiria'
Institutul Naţional de Boli Infecţioase „Prof. Dr. Matei Balş“
National Health Commission of the People's Republic of China
Pfizer Inc.
SBHI of the City of Moscow 'N.I.Pirogov City Clinical Hospital #1'
Corresponding Author(s)
Other Contributor(s)
Abstract
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.