Aztreonam-Ceftazidime/Avibactam Combination Dosing
Administer aztreonam 2 g IV every 8 hours simultaneously with ceftazidime/avibactam 2.5 g (2 g ceftazidime/0.5 g avibactam) IV every 8 hours via Y-site or separate infusions in adults with normal renal function. 1, 2
Adult Dosing (≥18 years)
Standard Regimen for Normal Renal Function
- Aztreonam: 2 g IV every 8 hours (infused over 20-60 minutes) 1
- Ceftazidime/avibactam: 2.5 g (2 g/0.5 g) IV every 8 hours (infused over 2 hours) 1
- Both agents can be administered via Y-site simultaneously without incompatibility at tested concentrations (aztreonam 10-20 mg/mL, ceftazidime/avibactam 8-50 mg/mL) 2
Renal Dose Adjustments
For Creatinine Clearance 31-50 mL/min:
For Creatinine Clearance 16-30 mL/min:
For Creatinine Clearance 6-15 mL/min:
- Aztreonam: 500 mg IV every 12 hours 1
- Ceftazidime/avibactam: 0.94 g (0.75 g/0.19 g) IV every 24 hours 1
- Note: Suboptimal probability of target attainment (≤71%) is predicted for ceftazidime/avibactam in this range; consider infectious disease consultation 3
For Hemodialysis Patients:
Pediatric Dosing (≥3 months)
Ages 3 to <6 months:
- Ceftazidime/avibactam: 40 mg/kg (ceftazidime component) IV every 8 hours, maximum 2000 mg ceftazidime per dose 1
- Aztreonam: Dosing not well-established in this age group; infectious disease consultation recommended 1
Ages ≥6 months to <18 years:
- Ceftazidime/avibactam: 50 mg/kg (ceftazidime component) IV every 8 hours, maximum 2000 mg ceftazidime per dose 1
- Aztreonam: Standard pediatric dosing is 30 mg/kg IV every 6-8 hours for serious infections, maximum 8 g/day 1
Neonatal Dosing (<3 months):
- Ceftazidime alone (avibactam combination not recommended in neonates):
- Gestational age <32 weeks, postnatal age <14 days: 50 mg/kg IV every 12 hours 1
- Gestational age <32 weeks, postnatal age ≥14 days: 50 mg/kg IV every 8 hours 1
- Gestational age ≥32 weeks, postnatal age ≤7 days: 50 mg/kg IV every 12 hours 1
- Gestational age ≥32 weeks, postnatal age >7 days: 50 mg/kg IV every 8 hours 1
Critical Administration Details
Infusion Logistics
- Ceftazidime/avibactam must be infused over 2 hours to maintain adequate avibactam concentrations 1, 3
- Aztreonam can be infused over 20-60 minutes 1
- Y-site compatibility is confirmed; no antagonism occurs when ceftazidime is present with aztreonam/avibactam 2, 4
Monitoring Requirements
- Baseline and periodic renal function assessment (serum creatinine, estimated GFR using CKD-EPI equation) 3
- Adjust doses based on calculated creatinine clearance, not just serum creatinine alone 3
- Monitor for hypersensitivity reactions to beta-lactams 1
Common Pitfalls to Avoid
- Do not use once-daily dosing: The combination requires every-8-hour administration to maintain synergistic activity against MBL-producing organisms 1, 5
- Do not omit renal dose adjustments: Failure to adjust for renal impairment increases toxicity risk and may lead to subtherapeutic levels 3
- Do not assume standard doses work in critically ill patients: Patients with burns, sepsis, or augmented renal clearance may require higher doses or therapeutic drug monitoring consultation 3
- Do not extrapolate adult dosing to neonates: Neonates have prolonged elimination and altered pharmacokinetics requiring weight- and age-based adjustments 1
Clinical Context
This combination is specifically designed for metallo-beta-lactamase (MBL)-producing Enterobacterales and Pseudomonas aeruginosa that co-express serine beta-lactamases 4, 5, 6. The avibactam component inhibits serine beta-lactamases (including KPC), protecting aztreonam from degradation, while aztreonam remains stable against MBLs (NDM, VIM, IMP) 4, 5. Synergy is achieved because ceftazidime acts as a "decoy" substrate, preventing MBL-mediated hydrolysis of aztreonam 6. In vitro studies demonstrate that 62.5% of resistant isolates shift to susceptible when this combination is used 5.