Aztreonam 1.5g / Avibactam 500mg powder for solution for infusion vials

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.

Abstract licence: CC BY

Abstract Introduction: Infections due to extended spectrum beta-lactam (ESBL) positive, carbapenemase producing enterobacteriaceae (CPE) and NDM1 resistance Enterobacteriaceae have significantly increased internationally and may account for up to 70% of infections in some geographies. Parallelly, high colistin resistance rates have also been reported. We are reporting the initial results of the first randomized-controlled trial addressing this issue of antibiotic resistant Gram-negative bacteremia (GNB). Objectives: The objective of the study was to assess the efficacy of first-line Ceftazidime–Avibactam with or without Aztreonam in high-risk FN, versus meropenem. Methodology: Adult patients with high-risk FN were randomized to Meropenem, Ceftazidime-Avibactum or Ceftazidime-Avibactum with Aztreonam as the first line antibiotic regimen. Results: Compared to meropenem, there was a trend towards reduced antibiotic failure, as defined by breakthrough fever within 7 days, with ceftazidime-avibactam, with or without aztreonam, although this wasn’t statistically significant, (p value = 0.076). Besides this, antibiotic failure was significantly associated with blood culture positivity (p= 0.015). Also, the presence of lung infiltrates was significantly associated with transfer to ICU (p=0.001). Conclusion: In high-risk FN, there was a trend to a higher incidence of antibiotic failure with first-line therapy with meropenem, compared to ceftazidime-avibactam with or without aztreonam, (p value = 0.076).

Abstract licence: CC BY 4.0