What is the role of Aztreonam (Aztreonam) with ceftazidime (Ceftazidime) plus avibactam (Avibactam) in treating infections?

Aztreonam Combined with Ceftazidime-Avibactam for MBL-Producing Resistant Infections

Aztreonam combined with ceftazidime-avibactam is the preferred treatment for serious infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales, demonstrating a dramatic reduction in 30-day mortality (19.2% vs 44%) compared to alternative therapies. 1, 2

Mechanistic Rationale for the Combination

The combination exploits complementary mechanisms of action:

• Aztreonam is not hydrolyzed by metallo-β-lactamases, making it uniquely active against MBL-producing organisms, but it remains susceptible to ESBLs and AmpC enzymes that these bacteria commonly co-produce 3, 4
• Avibactam (delivered via ceftazidime-avibactam) inhibits the ESBLs and AmpC enzymes that would otherwise destroy aztreonam, thereby protecting aztreonam and restoring its activity 3
• Ceftazidime in the combination does not interfere with aztreonam-avibactam activity, with MICs remaining within one 2-fold dilution regardless of ceftazidime concentration 5

Clinical Decision Algorithm Based on Carbapenemase Type

Obtain carbapenemase genotyping or phenotypic testing immediately upon suspecting carbapenem-resistant Enterobacterales infection 1, 3

For MBL-Producing CRE (NDM, VIM, IMP):

• Use ceftazidime-avibactam 2.5g IV every 8 hours (infused over 2-3 hours) PLUS aztreonam 1, 3
• This combination is strongly recommended with moderate-quality evidence 3

For KPC or OXA-48-Producing CRE:

• Use ceftazidime-avibactam 2.5g IV every 8 hours as monotherapy (aztreonam not needed) 1, 3
• Nearly 100% of KPC and OXA-48-producing strains are susceptible to ceftazidime-avibactam alone 3

Empiric Therapy When Carbapenemase Type Unknown:

• If local MBL prevalence is high: initiate ceftazidime-avibactam PLUS aztreonam 3
• If predominantly KPC/OXA-48 locally: ceftazidime-avibactam alone may suffice 3

Infection-Specific Treatment Durations

Complicated Urinary Tract Infections:

• 5-7 days of ceftazidime-avibactam plus aztreonam 1

Bloodstream Infections:

• 7-14 days of treatment 1
• The combination demonstrated 19.2% mortality versus 44% with other active antibiotics in a prospective study of 102 patients with MBL-producing Enterobacterales bacteremia 2

Hospital-Acquired or Ventilator-Associated Pneumonia:

• 10-14 days of treatment 1
• This is the preferred regimen for VAP caused by MBL-producing CRE, with superior outcomes compared to colistin-based regimens 1, 3

Complicated Intra-Abdominal Infections:

• 5-10 days of ceftazidime-avibactam plus aztreonam 1
• Add metronidazole 500mg IV every 6 hours for anaerobic coverage 1, 6

Important Clinical Caveats

• This combination is ineffective against non-MBL resistance mechanisms in Pseudomonas aeruginosa, so carbapenemase identification is critical before relying on this regimen 3
• The combination is specifically for MBL-producing organisms; using it for non-MBL CRE wastes aztreonam and adds unnecessary drug exposure 1, 3
• Aztreonam-avibactam as a single fixed-dose combination product has been approved in Europe and offers a simpler alternative to combining two separate products 6
• Standard dosing appears adequate for most patients, including critically ill individuals, when adjusted for renal function using eGFR 7