By IDSE News Staff
The FDA approved aztreonam-avibactam (Emblaveo, AbbVie), the first and only fixed-dose, IV monobactam/beta-lactamase inhibitor combination antibiotic to be used with metronidazole, to treat complicated intraabdominal infections (cIAIs), including those caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex and Serratia marcescens.
Approval of this indication for patients 18 years of age and older with limited or no other alternatives is based on limited clinical safety and efficacy data for aztreonam-avibactam.
The phase 3 REVISIT clinical trial is a randomized, active-controlled, central assessor-blinded multicenter trial evaluating aztreonam-avibactam plus/minus metronidazole versus the combination of meropenem plus/minus colistin in patients with cIAIs or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (not an approved indication for aztreonam-avibactam). The study enrolled 422 patients across 81 locations globally. The primary end point was clinical cure at the test-of-cure visit in the intent-to-treat (ITT) population. Secondary end points included 28-day mortality in the ITT population safety in patients in the ITT population who received the study drug. The REVISIT trial included 312 hospitalized patients with cIAIs who were randomized 2:1 to receive treatment with aztreonam-avibactam with metronidazole or meropenem plus/minus colistin for five to 14 days of therapy. The trial was not designed with any formal hypotheses for inferential testing against the active comparator.
More information on the study can be found on www.clinicaltrials.gov (NCT03329092) and in The Lancet Infectious Diseases (2025;25[2]:218-230).
Gram-negative bacterial infections are among the most challenging for healthcare professionals to control due to high antimicrobial resistance (AMR), according to the WHO.
“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, Milefchik-Rand Medical Group, at Torrance Memorial Medical Center, in California. “The approval of Emblaveo provides physicians a much-needed therapeutic option to help address some of the most difficult antimicrobial-resistant pathogens and provides doctors an opportunity to treat patients with these challenging infections.”
Emblaveo combines aztreonam, a monobactam antibiotic, and avibactam, a beta-lactamase inhibitor that protects aztreonam from serine beta-lactamase hydrolysis and restores its activity against bacteria that coproduce metallo-beta-lactamases and serine beta-lactamases (J Glob Antimicrob Resist 2022;30:214-221).
AMR is considered an urgent global public health threat and could lead to more than 39 million deaths worldwide by 2050 (Lancet 2024;404[10459]:1199-1226). An estimated 1.14 million deaths globally were attributed to bacterial AMR in 2021 alone. The FDA has prioritized the research and development of new medicines to treat AMR and help prevent the spread of infection.
“As bacteria evolve, industry, government, and clinical experts must work together to ensure that the infectious disease community has the tools to advance public health,” said Roopal Thakkar, MD, the executive vice president of Research and Development and chief scientific officer at AbbVie.
In 2019, the FDA granted Qualified Infectious Disease Product and Fast Track designations for aztreonam-avibactam, which provides certain incentives for the development of new antibiotics, including Priority Review and eligibility for the FDA’s Fast Track designation, and a five-year regulatory exclusivity extension. The Fast Track designation is designed to facilitate the development of and accelerate the review of drugs to treat serious conditions that do not have sufficient treatment options.
Aztreonam-avibactam was developed jointly with Pfizer. AbbVie holds the rights to commercialize the therapy in the United States and Canada, with Pfizer responsible for commercialization in all other areas. Development was also supported by public–private partnerships with the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, and through the EU's Innovative Medicines Initiative—a partnership between the EU and the European pharmaceutical industry—under a project called Combatting Bacterial Resistance in Europe–Carbapenem Resistance (COMBACTE-CARE). The COMBACTE-CARE consortium is a unique public–private collaboration that unites the knowledge and capabilities of leading drug-resistant bacterial infection experts and is supported by the COMBACTE pan-European clinical and laboratory networks.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of aztreonam-avibactam and other antibacterial drugs, aztreonam-avibactam should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
The most common adverse reactions occurring at an incidence of greater than 5% were hepatic reactions, anemia, diarrhea, hypokalemia and pyrexia. The FDA encourages people to report adverse events to Medwatch or call 1-800-FDA-1088. Please click here for the full prescribing information.
Aztreonam-avibactam will be available for commercial use in the United States in the third quarter of 2025.
