EMBLAVEO (aztreonam/avibactam) - Metallo-β-lactamase

The Committee deems that the clinical benefit of EMBLAVEO (aztreonam/avibactam) is substantial in complicated intra-abdominal infection, hospital-acquired pneumonia/ventilator-associated pneumonia, complicated urinary tract infection, including pyelonephritis and infections due to aerobic Gram-negative organisms in adult patients with limited treatment options, only as a last resort, for the treatment of patients with infections caused by Enterobacterales with a metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]) or by Stenotrophomonas maltophilia, susceptible to the aztreonam/avibactam combination, and for whom the use of the 
other antibiotics available is not appropriate in the event of resistance. 

Considering:

• its in vitro activity on a broad variety of Gram-negative bacteria, such as carbapenem-resistant Enterobacterales with a metallo-β-lactamase resistance mechanism [NDM, VIM, IMP] or non fermenter bacteria such as Stenotrophomonas maltophilia;
• the efficacy suggested in phase 3, descriptive, comparative studies (C3601009 and C3601002);
• experience acquired with aztreonam, already widely used in the treatment of severe infections due to aerobic Gram-negative bacteria;
• the fact that the ceftazidime/avibactam and aztreonam combination is already used as the reference treatment for MBL-producing Enterobacterales. It should be noted that the microbiological benefit of this combination is based only on the aztreonam and avibactam combination (since ceftazidime has no activity on this type of resistance mechanism). The use of two antibiotics therefore exposes patients to a risk of needless iatrogenic effects and may have a detrimental ecological impact; 
• the known and acceptable safety profile of aztreonam, the only representative of the monobactam class, and of avibactam (through its combination with ceftazidime in ZAVICEFTA) which is already used, with no new safety signals with the aztreonam/avibactam combination; 

but: 

• limited clinical data, particularly in severe forms and/or forms due to multi-drug resistant bacteria, given:
  • the descriptive nature of the two phase 3, comparative studies (C3601009 and C3601002) suggesting an efficacy in complicated urinary tract infections (including pyelonephritis), complicated intra-abdominal infections, as well as in hospital-acquired pneumonia and ven tilator associated pneumonia and sepsis due to Gram-negative bacilli,
  • the small number of patients included in these studies, in particular patients with severe MBL-producing Gram-negative bacilli infections,

the Committee deems that EMBLAVEO (aztreonam/avibactam) provides a minor clinical added value (CAV IV) in the treatment of complicated intra-abdominal infection, hospital-acquired pneumonia/ventilator-associated pneumonia, complicated urinary tract infection, including pyelonephritis and infections due to aerobic Gram-negative organisms in adult patients with limited treatment options, only as a last resort, for the treatment of patients with infections caused by Enterobacterales with a metallo-β-lactamase resistance mechanism [NDM, VIM, IMP]) or by Stenotrophomonas maltophilia, susceptible to the aztreonam/avibactam combination, and for whom the use of the other antibiotics available is not appropriate in the event of resistance.