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.Mahidol University2025-08-042025-08-042025-08-01Jac Antimicrobial Resistance Vol.7 No.4 (2025)https://repository.li.mahidol.ac.th/handle/123456789/111539Background 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.MedicineImmunology and MicrobiologyArticleSCOPUS10.1093/jacamr/dlaf1312-s2.0-10501186712926321823