Evaluating the Susceptibility of MBL Carbapenemase-Producing Enterobacteriaceae and Pseudomonas spp. to Ceftazidime/Avibactam plus aztreonam and Cefiderocol: A Synergy Study Using the gradient strip stacking method and Susceptibility profile to the novel combination by gradient Concentration Strips.

Purpose This study investigates the in vitro effectiveness of the combination aztreonam and ceftazidime/avibactam (ATM/CZA) against metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas spp., using the gradient strip stacking method to evaluate synergy, and compares it with the novel aztreonam/avibactam (ATM/AVI) combination. Susceptibility to cefiderocol and other antimicrobials was studied. Methods A total of 38 non-duplicate strains were analyzed: 31 Enterobacterales and 7 Pseudomonas spp., all confirmed carbapenemase MBL producers. Results ATM/AVI showed 100% susceptibility among Enterobacterales using epsilon test method according to EUCAST breakpoints, although synergy AZT plus CZA was found in only 58% of the strains. The 100% of aztreonam-resistant strains showed synergy, compared to only 18.8% of aztreonam-susceptible strains, suggesting that the combination provides greater benefit in resistant strains. In contrast, Pseudomonas spp. strains showed minimal synergy as previous reported(14.3%) and low susceptibility (1/7 strains) to the ATM/AVI combination, highlighting the limited efficacy of this therapy against these organisms. Cefiderocol, however, demonstrated high activity: 93.5% susceptibility in Enterobacterales group and 100% in Pseudomonas spp. Conclusion The study emphasizes that gradient strips test may not reveal which aztreonam-susceptible strains would benefit from the ATM/AVI combination, therefore, synergy testing remains crucial. Ultimately, ATM/AVI is a promising option for treating infections caused by MBL-producing Enterobacterales, while cefiderocol remains a important agent against MBL-producing Pseudomonas spp.