Recommended Dosage of Ceftazidime-Avibactam with Aztreonam for Complicated Infections
For complicated infections requiring ceftazidime-avibactam with aztreonam, the recommended dosage is ceftazidime-avibactam 2.5 g (ceftazidime 2 g and avibactam 0.5 g) IV every 8 hours administered over 2 hours, plus aztreonam at standard dosing. 1
Dosing Recommendations by Infection Type
For Complicated Intra-abdominal Infections (cIAI)
- Ceftazidime-avibactam 2.5 g IV q8h (infused over 2 hours) + metronidazole 500 mg q6h 2, 1
- Treatment duration: 5-7 days, individualized based on source control and clinical response 2
- When adding aztreonam for suspected or confirmed metallo-β-lactamase (MBL) producers, standard aztreonam dosing can be used without concern for antagonism with ceftazidime-avibactam 3
For Complicated Urinary Tract Infections (cUTI)
- Ceftazidime-avibactam 2.5 g IV q8h (infused over 2 hours) 2, 1
- Treatment duration: 5-7 days for cUTI 2
- For carbapenem-resistant Enterobacterales (CRE), ceftazidime-avibactam is a recommended option 2
For Bloodstream Infections
- Ceftazidime-avibactam 2.5 g IV q8h (infused over 2 hours) 2
- Treatment duration: 7-14 days 2
- For CRE bloodstream infections, ceftazidime-avibactam is recommended with a weak recommendation (2D) 2
Special Considerations for Renal Function
- For patients with creatinine clearance (CrCl) >50 mL/min: Standard dose of 2.5 g IV q8h 1
- For patients with renal impairment: Dose adjustment is required as both ceftazidime and avibactam are primarily eliminated through renal clearance 1, 4
- Caution: Recent evidence suggests that renal-adjusted dosing of ceftazidime-avibactam may be associated with higher mortality in bloodstream infections caused by KPC-producing Klebsiella pneumoniae 5
Infusion Considerations
- Standard infusion time is 2 hours for ceftazidime-avibactam 1
- For severe infections, especially in patients with augmented renal clearance, extending infusion time to 3-4 hours may improve target attainment 6
- Continuous infusion may be considered for severe infections requiring higher drug concentrations 6
Combination with Aztreonam for MBL-producing Organisms
- When treating suspected or confirmed metallo-β-lactamase-producing organisms, the addition of aztreonam to ceftazidime-avibactam is recommended 3
- Studies show that ceftazidime in the combination does not affect the in vitro activity of aztreonam/avibactam against MBL-producing Enterobacterales 3
- This combination effectively addresses organisms that produce both serine β-lactamases and metallo-β-lactamases 3
Pharmacokinetic/Pharmacodynamic Considerations
- The PK/PD target for ceftazidime is 50% free time above MIC (fT > MIC) 4, 7
- The PK/PD target for avibactam is 50% free time above threshold concentration of 1 mg/L (fT > CT) 4, 7
- For severe infections, higher targets may be necessary, potentially requiring extended or continuous infusion 6
Common Pitfalls and Caveats
- Inadequate dosing in patients with augmented renal clearance may lead to treatment failure 6
- Renal dose adjustment may result in suboptimal exposure in certain clinical scenarios 5
- Continuous monitoring of renal function is essential as changes may necessitate dose adjustments 1
- Treatment duration should be individualized based on infection site, source control, underlying comorbidities, and initial response to therapy 2
Remember that ceftazidime-avibactam alone is not effective against metallo-β-lactamase-producing organisms, which is why aztreonam is added in these cases 3.