Aztreonam-avibactam (Emblaveo) photo source pfizer.nl
KEY POINTS
- Aztreonam-avibactam (Emblaveo) is the combination of aztreonam (a monobactam) that interferes with bacterial cell wall synthesis and avibactam (a β-lactamase inhibitor) that neutralizes β-lactamase enzymes
- Aztreonam is only active against gram negative bacteria
- Is not hydrolyzed by ambler class B β-lactamases (e.g., NDM, VIM, IMP) which are metallo-β-lactamases (MBL)
- Does not have anaerobic activity
- Avibactam can inhibit ambler class A, class C, and some class D β-lactamases. It does not inhibit MBL-producing gram negative bacteria.
- There are few options for MBL-producing gram negative bacteria, but aztreonam-avibactam can be an option:
- MBLs do not hydrolyze aztreonam so it can be used for MBLs, however bacteria that produce MBLs often co-produce other β-lactamases that hydrolyze aztreonam. Avibactam protects aztreonam from being hydrolyzed by these other co-produced β-lactamases.
- Aztreonam is only active against gram negative bacteria
- For years there was no commercially available product for aztreonam-avibactam, so ceftazidime-avibactam (Avycaz) has been combined with aztreonam (Azacatam) to enable delivering aztreonam with avibactam.
- Aztreonam-avibactam was approved with Pfizer by the European Commission on 22 April 2024 for patients with multi-drug resistant infections and limited treatment options, cited to be able to be used for:
- Complicated intra-abdominal infections (cIAI)
- Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP),
- Complicated urinary tract infections (cUTI), including pyelonephritis.
- Aztreonam-avibactam was approved with Abbvie by FDA on 7 February 2025 for use in combination with metronidazole to treat adult patients with no or limited treatment options that have cIAI caused by a susceptible organism
- Listed organisms include Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae complex, Citrobacter freundii complex, and Serratia marcescens
- Metronidazole is added to provide anti-anaerobic coverage
- The IDSA guideline on the treatment of infections caused by resistant gram negative bacteria is a key resource for knowing when aztreonam-avibactam may be an option
- See discussions on treatment of infections due to carbapenem-resistant Enterobacterales (CRE) in the presence of MBLs as well as discussions on treatment of Stenotrophomonas maltophilia
- For adults with normal renal function, requires a 3-hour infusion administered every 6 hours
- Requires dose and/or frequency adjustments for renal function
- Beware cross-hypersensitivity reaction between aztreonam and ceftazidime (i.e., if a patient has an allergy to one, they may have an allergy to the other due to similar chemical structures)
- Has warnings and precautions for serious skin disorders (e.g., toxic epidermal necrolysis), hepatic adverse reactions, and C. difficile-associated diarrhea
- Supplied in packs of 10 clear vials that contain a powder for reconstitution, which are to be stored at 36-46 degrees fahrenheit (2-8 degrees celsius), protected from light
- Each vial contains 1.5 grams of aztreonam and 0.5 grams of avibactam
- Vial should be used within 30 minutes to make the dose, but diluted dose can be good for 24 hours when refrigerated and handled appropriately (details in FDA label)
A few major questions for this product in 2025 include:
- When will it be commercially available for use in the United States?
- What will be the cost for this product versus ceftazidime-avibactam plus aztreonam as separate products?
- How accessible will susceptibility testing be for aztreonam-avibactam from microbiology labs?
RESOURCES
- Aztreonam-Avibactam (Emblaveo) American Package Insert
- Aztreonam-Avibactam (Emblaveo) European Package Insert
- Pfizer release on aztreonam-avibactam (Emblaveo) European approval
- Abbvie release on aztreonam-avibactam (Emblaveo) FDA approval
- Metallo-β-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline (AAC 2020)
- Dose selection for aztreonam-avibactam, including adjustments for renal impairment, for Phase IIa and Phase III evaluation (EJCP 2024)
- Phase 3 Studies of Pfizer’s Novel Antibiotic Combination Offer New Treatment Hope for Patients with Multidrug-Resistant Infections and Limited Treatment Options (Pfizer 2023)
- Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study (JAC 2020)
- 2893 A. Efficacy and Safety of Aztreonam-Avibactam for the Treatment of Serious Infections Due to Gram-Negative Bacteria, Including Metallo-β-Lactamase-Producing Pathogens: Phase 3 REVISIT Study (OFID 2023)
- In vitro activity of aztreonam/avibactam against isolates of Enterobacterales collected globally from ATLAS in 2019 (JGAR 2022)