Administration of Aztreonam and Ceftazidime-Avibactam Combination
For an adult with normal renal function, administer aztreonam 2 grams IV every 6-8 hours plus ceftazidime-avibactam 2.5 grams (2 grams ceftazidime/0.5 grams avibactam) IV every 8 hours, with both agents infused over 2 hours and compatible for Y-site co-administration. 1
Dosing Regimen
Standard Dosing for Normal Renal Function
- Aztreonam: 2 grams IV every 6-8 hours, infused over 2 hours 2
- Ceftazidime-avibactam: 2.5 grams (2 grams ceftazidime/0.5 grams avibactam) IV every 8 hours, infused over 2 hours 2
- Both agents should be administered as extended infusions (2-4 hours) to optimize pharmacokinetic/pharmacodynamic properties 3, 2
Reconstitution and Dilution
- Ceftazidime-avibactam should be reconstituted and diluted to concentrations of 8-50 mg/mL in 0.9% sodium chloride 1
- Aztreonam should be reconstituted and diluted to concentrations of 10-20 mg/mL 1
- These concentration ranges have been validated for compatibility 1
Administration Method
Y-Site Compatibility
The combination is fully compatible for Y-site co-administration, allowing simultaneous infusion through the same IV line. 1
- Visual, microscopic, turbidity, and pH testing demonstrated no incompatibility across all concentration combinations 1
- No particulate matter, color changes, or turbidity observed over 12 hours after mixing 1
- Compatibility maintained regardless of which agent is added first 1
Infusion Duration
- Both agents should be infused over 2 hours to optimize drug exposure and minimize toxicity 2
- Extended 4-hour infusions may be considered for aztreonam when targeting organisms with MIC of 8 mg/L 3, 2
Renal Function Adjustments
Monitoring Requirements
- Estimate glomerular filtration rate (eGFR) using CKD-EPI equation, as this predicts clearance for both aztreonam and ceftazidime-avibactam 2
- Reassess renal function if clinical status changes, particularly in critically ill patients 2
Dose Modifications for Renal Impairment
- eGFR 51-90 mL/min: Consider pragmatic lower daily doses based on pharmacokinetic modeling 2
- eGFR 30-50 mL/min: Dose reduction required for ceftazidime-avibactam; specific adjustments needed 3
- eGFR 6-15 mL/min: Suboptimal probability of target attainment (≤71%) predicted for ceftazidime-avibactam, requiring careful monitoring 2
- eGFR <30 mL/min: Contraindicated or requires significant dose adjustment for ceftazidime-avibactam 3
Clinical Efficacy Evidence
Mortality Benefit
The combination demonstrates significant mortality reduction compared to other active antibiotics for metallo-β-lactamase-producing Enterobacterales bloodstream infections. 4
- 30-day mortality: 19.2% with aztreonam plus ceftazidime-avibactam versus 44% with other active antibiotics (P = 0.007) 4
- Propensity score-adjusted hazard ratio for mortality: 0.37 (95% CI 0.13-0.74, P = 0.01) 4
- Clinical failure at day 14: HR 0.30 (95% CI 0.14-0.65, P = 0.002) 4
Microbiological Activity
- Effective against NDM-producing and VIM-producing Enterobacterales 4
- Ceftazidime in the triple combination does not antagonize aztreonam-avibactam activity, with MICs remaining within one 2-fold dilution 5
- Ceftazidime-avibactam shows more reliable activity than aztreonam-avibactam against carbapenemase-independent carbapenem-resistant Enterobacterales 6
Common Pitfalls to Avoid
- Do not use standard infusion times (<1 hour): Extended infusions are critical for optimizing time above MIC 2
- Do not assume incompatibility: The agents are fully compatible for Y-site administration despite theoretical concerns 1
- Do not neglect renal function monitoring: Both agents require dose adjustment in renal impairment, with eGFR being the best predictor of clearance 2
- Do not delay therapy: The combination shows superior outcomes when used as definitive therapy for MBL-producing organisms 4