Recommended Aztreonam Dosing with Ceftazidime-Avibactam
For metallo-β-lactamase-producing carbapenem-resistant Enterobacterales (CRE) infections, aztreonam should be dosed at 2 grams IV every 6-8 hours when combined with ceftazidime-avibactam 2.5 grams IV every 8 hours, administered simultaneously as prolonged infusions. 1
Standard Dosing Regimen
The optimal combination regimen based on hollow-fiber infection model studies and clinical outcomes is:
- Aztreonam: 2 grams IV every 6 hours (total daily dose 8 g/day) 2
- Ceftazidime-avibactam: 2.5 grams IV every 8 hours 1
- Infusion duration: 2-3 hours for both agents 2, 3
- Administration timing: Simultaneous, not staggered 2
Rationale for This Dosing Strategy
The higher aztreonam dose of 8 g/day (2 g every 6 hours) demonstrates superior bacterial killing and resistance suppression compared to 6 g/day regimens against NDM-producing strains. 2 Prolonged infusions (2-3 hours) significantly enhance bacterial eradication compared to standard 30-minute infusions. 2, 3 Simultaneous administration is critical—staggered dosing (ceftazidime-avibactam followed by aztreonam) results in inferior outcomes. 2
Clinical Evidence Supporting This Combination
This combination achieved a 30-day mortality rate of 19.2% in patients with metallo-β-lactamase-producing CRE bloodstream infections, compared to 44% with other antimicrobial agents (HR: 0.37,95% CI 0.13-0.74). 1 Clinical treatment failure rates were also significantly lower (HR: 0.30,95% CI 0.14-0.65). 1
Mechanism and Microbiologic Activity
Aztreonam is not hydrolyzed by metallo-β-lactamases (NDM, VIM, IMP), making it uniquely active against these organisms. 1, 4 However, MBL-producing strains often co-produce other β-lactamases (AmpC, ESBL, OXA-48) that degrade aztreonam. 5 Avibactam inhibits these co-produced enzymes, restoring aztreonam activity. 1
In vitro synergy studies show this combination achieves MIC ≤4 mg/L in approximately 80% of MBL-producing Enterobacterales. 5
Treatment Duration by Infection Type
- Bloodstream infections: 7-14 days 1, 6
- Complicated urinary tract infections: 5-7 days 1, 6
- Hospital-acquired/ventilator-associated pneumonia: 10-14 days 1, 6
- Complicated intra-abdominal infections: 5-7 days 1, 6
Continue therapy for at least 48 hours after clinical improvement or bacterial eradication. 6, 3
Critical Implementation Considerations
Identify carbapenemase type before treatment initiation whenever possible. 1 This combination is specifically indicated for metallo-β-lactamase producers (NDM, VIM, IMP), not for KPC or OXA-48-only producers where ceftazidime-avibactam alone may suffice. 1
Y-site compatibility is confirmed at concentrations of ceftazidime-avibactam 8-50 mg/mL with aztreonam 10-20 mg/mL, allowing simultaneous administration through the same IV line. 7
Important Caveats
- Pseudomonas aeruginosa with MBLs: This combination shows poor activity (only 6% susceptibility), requiring alternative strategies. 5
- Renal dosing adjustments: Aztreonam clearance is directly proportional to creatinine clearance and requires dose reduction in renal insufficiency. 8
- Resistance emergence: Prior ceftazidime-avibactam exposure increases risk of resistance development in carbapenemase-producing organisms. 6
- Additional agents: Some protocols include polymyxin or fosfomycin for critically ill patients or when MICs are elevated. 1