Dosing of Aztreonam and Ceftazidime-Avibactam for Severe Infections
For severe infections, ceftazidime-avibactam should be dosed at 2.5 g IV every 8 hours infused over 2 hours, and aztreonam at 2 g IV every 6-8 hours for systemic infections. 1, 2
Ceftazidime-Avibactam Dosing
Standard Adult Dosing
- 2.5 g (ceftazidime 2 g + avibactam 0.5 g) IV every 8 hours, infused over 2 hours 1
- This applies to patients ≥18 years with creatinine clearance >50 mL/min 1
- For complicated intra-abdominal infections, must be combined with metronidazole 500 mg IV every 6-8 hours 3, 4
Duration by Infection Type
- Bloodstream infections: 7-14 days 3
- Complicated urinary tract infections: 5-7 days 3
- Complicated intra-abdominal infections: 5-7 days 3
- Hospital-acquired/ventilator-associated pneumonia: 7-14 days 1
Pediatric Dosing (≥2 years)
- 62.5 mg/kg (maximum 2.5 g) IV every 8 hours for children 2 to <18 years with eGFR >50 mL/min/1.73 m² 1
- Younger children require weight-based adjustments: 50 mg/kg for 3-6 months, 37.5 mg/kg for >28 days to <3 months, and 25 mg/kg for ≤28 days with gestational age ≥31 weeks 1
Renal Dose Adjustments
Ceftazidime-avibactam requires careful dose reduction in renal impairment to prevent neurotoxicity (seizures, encephalopathy, confusion) 5. The FDA label provides specific adjustments based on creatinine clearance, though exact values are referenced in the full prescribing information 1.
Extended Infusion Considerations
For severe infections, particularly with augmented renal clearance or higher MIC organisms, extending infusion time to 3-4 hours may be necessary to achieve optimal pharmacodynamic targets 6. Continuous infusion at higher dosages may be required for the most resistant organisms 6.
Aztreonam Dosing
Standard Adult Dosing
- For severe systemic or life-threatening infections: 2 g IV every 6-8 hours 3, 2
- For moderately severe systemic infections: 1-2 g IV every 8-12 hours 2
- For urinary tract infections: 500 mg to 1 g every 8-12 hours 2
Pseudomonas aeruginosa Infections
2 g every 6-8 hours is specifically recommended for Pseudomonas infections, at least upon initiation of therapy, due to the serious nature of these infections 2. This higher dosing achieves MIC90 values for P. aeruginosa for almost 6 hours after a 2 g dose 7.
Pediatric Dosing
- Moderate to severe infections: 30 mg/kg IV every 6-8 hours (maximum 120 mg/kg/day) 2
- Mild to moderate infections: 30 mg/kg IV every 8 hours 2
- Administer intravenously to pediatric patients with normal renal function 2
Renal Dose Adjustments
- CrCl 10-30 mL/min/1.73 m²: Halve the dose after initial loading dose of 1-2 g 2
- CrCl <10 mL/min/1.73 m² (including hemodialysis): Give usual initial dose, then one-fourth of initial dose at usual intervals, plus one-eighth of initial dose after each hemodialysis session 2
Combination Therapy: Aztreonam + Ceftazidime-Avibactam
For metallo-beta-lactamase (MBL)-producing carbapenem-resistant Enterobacterales, the combination of aztreonam with ceftazidime-avibactam is specifically recommended 3. This combination showed significantly lower 30-day mortality (HR 0.37,95% CI 0.13-0.74) compared to other therapies for MBL-producing CRE bacteremia 3.
Key Clinical Considerations
Common Pitfalls:
- Failing to add metronidazole when using ceftazidime-avibactam for intra-abdominal infections 3, 4
- Inadequate dose adjustment in renal impairment, risking neurotoxicity with ceftazidime-avibactam 5
- Using standard 2-hour infusions when extended infusions may be needed for severe infections or resistant organisms 6
- Underdosing aztreonam for Pseudomonas infections—always use 2 g every 6-8 hours initially 2
Duration of therapy should be continued for at least 48 hours after the patient becomes asymptomatic or evidence of bacterial eradication is obtained 2. Persistent infections may require several weeks of treatment 2.