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: = 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.