IDStewardship

Aztreonam-avibactam (Emblaveo)

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.
  • 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?

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