Optimism After Open-Label Study as Rising Carbapenem Resistance Shapes Future Treatment Guidance

The recent open-label evaluation of aztreonam-avibactam has raised important questions about how clinicians should interpret its results and how the drug may ultimately fit into treatment strategies for multidrug-resistant infections. Because aztreonam-avibactam requires a four-times-daily dosing schedule—unlike comparator regimens such as meropenem–colistin—a blinded study design was not feasible. As a result, clinicians must interpret the findings with an understanding of the inherent limitations of open-label trials, including the potential for subconscious bias or preferential management. Still, experts note that no clear signs of differential treatment emerged, and the clinical need for agents targeting metallo-β-lactamase (MBL) producers is substantial.

Confidence in aztreonam-avibactam would be strengthened by continued real-world, post-marketing data, especially as outcomes in severely ill patients often depend on comorbidities unrelated to infection. This pattern echoes earlier antimicrobial experiences—such as tigecycline—where strong in-vitro activity did not fully translate to critically ill populations. Encouragingly, clinicians have already used aztreonam-avibactam-based combinations in modified forms for years, with recently published data demonstrating robust activity against MBL-producing Enterobacterales.

As carbapenem resistance accelerates, aztreonam-avibactam is expected to play an increasingly important role. Although the FDA indication does not yet include hospital-acquired or ventilator-associated pneumonia, clinicians frequently use newer agents off-label when treating severe multidrug-resistant infections. Experts anticipate that IDSA’s annually updated guidance documents will likely incorporate aztreonam-avibactamas more evidence accumulates—particularly for complicated intra-abdominal infections and potentially severe pneumonias caused by MBL producers or resistant Stenotrophomonas. Given the scarcity of effective options, the drug is poised to become an essential tool as resistance patterns evolve.