The U.S. Food and Drug Administration has approved aztreonam-avibactam (EMBLAVEO) in combination with metronidazole in patients aged 18 years and older with complicated intra-abdominal infections who have limited or no alternative treatment options. This marks the first approval of a monobactam/beta-lactamase inhibitor combination antibiotic therapy, which was based on limited clinical safety and efficacy data.
The novel treatment is specifically indicated for infections caused by susceptible gram-negative microorganisms, including Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens, according to a press release from Abbvie.
The approval was supported by the phase III REVISIT trial, which enrolled 312 hospitalized patients with complicated intra-abdominal infections (cIAI) across 81 locations globally. The patients were randomly assigned 2:1 to receive either aztreonam-avibactam with metronidazole or meropenem with or without colistin for 5 to 14 days.
The mechanism of action combines aztreonam, a monobactam antibiotic, with avibactam, a beta-lactamase inhibitor. Avibactam protects aztreonam from serine beta-lactamase hydrolysis and restores its activity against bacteria that co-produce Metallo-beta-lactamases (MBL) and serine beta-lactamases.
"The continued evolution of antimicrobial resistance among gram-negative bacteria has left some patients with little to no treatment options, resulting in extended hospital stays, additional morbidity, and death," said James A. McKinnell, MD, an infectious disease specialist at the Milefchik-Rand Medical Group at the Torrance Memorial Medical Center in Torrance, California.
The most frequent adverse reactions occurring in more than 5% of patients were hepatic adverse reactions, anemia, diarrhea, hypokalemia, and pyrexia. The drug is contraindicated in patients with known hypersensitivity to aztreonam or avibactam.
Important safety considerations include monitoring for hypersensitivity reactions, serious skin disorders like toxic epidermal necrolysis, hepatic adverse reactions, and Clostridioides difficile–associated diarrhea. Liver function monitoring is recommended during treatment, particularly in patients with baseline liver comorbidities or those taking concomitant hepatotoxic medications.
The drug received both Qualified Infectious Disease Product Designation and Fast Track Designation from the U.S. Food and Drug Administration in 2019. Commercial availability in the United States is expected in the third quarter of 2025.
The approval comes amid growing concerns about antimicrobial resistance, with recent estimates suggesting that bacterial antimicrobial resistance contributed to approximately 1.14 million deaths globally in 2021. Without intervention, antimicrobial resistance could lead to over 39 million deaths worldwide by 2050.
The European Commission granted marketing authorization for aztreonam-avibactam in April 2024 for a broader range of indications, including hospital-acquired pneumonia, ventilator-associated pneumonia, and complicated urinary tract infections. The marketing authorization was subsequently approved in Great Britain in June 2024.
The development of aztreonam-avibactam was supported through public-private partnerships, including collaboration with the U.S. Department of Health and Human Services and the EU's Innovative Medicines Initiative.
