Aztreonam-Avibactam Dosing for Bacterial Infections
For aztreonam-avibactam combination therapy, administer 500 mg/167 mg IV loading dose over 30 minutes, followed by 1500 mg/500 mg IV every 6 hours infused over 3 hours for patients with normal renal function. 1, 2
Standard Dosing Regimen
The approved aztreonam-avibactam regimen consists of:
- Loading dose: 500 mg aztreonam/167 mg avibactam IV over 30 minutes 1
- Maintenance dose: 1500 mg aztreonam/500 mg avibactam IV every 6 hours, infused over 3 hours 1, 2
This fixed 3:1 ratio achieves optimal joint pharmacodynamic target attainment (aztreonam 60% fT >8 mg/L and avibactam 50% fT >2.5 mg/L) across infection types. 2
Infection-Specific Dosing
Complicated Intra-Abdominal Infections
- Ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 2 hours) + metronidazole 500 mg every 6 hours 3
- Duration: 5-7 days, individualized based on source control and clinical response 3
Complicated Urinary Tract Infections
Bloodstream Infections (Including CRE)
- Ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 2 hours) 3
- Duration: 7-14 days 3, 4
- Consider prolonged 3-hour infusion for improved 30-day survival 4
Hospital-Acquired/Ventilator-Associated Pneumonia
Renal Dose Adjustments
Creatinine clearance is the critical determinant for dose modification. 5
Moderate Renal Impairment (CrCl >30 to ≤50 mL/min)
Severe Renal Impairment (CrCl >15 to ≤30 mL/min)
End-Stage Renal Disease (CrCl <10 mL/min)
- Standard initial dose followed by one-fourth maintenance dose 5
- Give one-eighth of initial dose after each hemodialysis session 5
Monotherapy Aztreonam Dosing (When Used Alone)
For aztreonam monotherapy without avibactam:
Standard Adult Dosing
- Urinary tract infections: 500 mg to 1 g IV every 8-12 hours 5
- Moderately severe systemic infections: 1-2 g IV every 8-12 hours 5
- Severe/life-threatening infections: 2 g IV every 6-8 hours 5
- Pseudomonas aeruginosa infections: 2 g IV every 6-8 hours (at least initially) 5
Pediatric Dosing (≥1 month to 12 years)
- Mild-moderate infections: 30 mg/kg IV every 8 hours 5
- Moderate-severe infections: 30 mg/kg IV every 6-8 hours 5
- Maximum: 120 mg/kg/day 5
Critical Clinical Considerations
For Metallo-β-Lactamase Producers
The combination of ceftazidime-avibactam with aztreonam demonstrates significantly lower mortality (19.2% vs 44%) compared to other regimens for metallo-β-lactamase-producing carbapenem-resistant organisms. 4 This combination shows good in-vitro synergy because aztreonam is not hydrolyzed by metallo-β-lactamases. 4
Infusion Duration Matters
- Standard 3-hour infusions optimize pharmacodynamic target attainment 1, 2
- Prolonged infusions (3 hours) associated with improved survival outcomes 4
- Loading doses support more rapid target attainment 1
Monitoring Requirements
- Monitor for neurotoxicity (seizures, encephalopathy, confusion), particularly in renal impairment 6
- Clinical improvement should be evident within 48-72 hours 4
- Ascertain carbapenemase type before initiating ceftazidime-avibactam when possible 4
Common Pitfalls to Avoid
Do not use IDSA-recommended ceftazidime-avibactam + aztreonam regimens for metallo-β-lactamase producers—they achieve joint PTA <85% due to insufficient avibactam exposures. 2 Use the approved fixed-ratio aztreonam-avibactam formulation instead.
Do not discontinue therapy prematurely before clinical stability is achieved. 4 Continue for at least 48 hours after symptom resolution. 5
Do not use serum creatinine alone in elderly patients—calculate creatinine clearance using the Cockcroft-Gault formula to guide dosing. 5
Avoid underdosing in complicated intra-abdominal infections—these patients have the lowest drug exposures and require full dosing. 2