Ceftazidime-Avibactam Dosing in Adults with Normal Renal Function
For adults with normal renal function (CrCL >50 mL/min), administer ceftazidime-avibactam 2.5 grams (ceftazidime 2 grams + avibactam 0.5 grams) IV every 8 hours as a 2-hour infusion. 1, 2, 3
Standard Dosing Regimen
The fixed-dose combination maintains a 4:1 ratio of ceftazidime to avibactam (2000 mg:500 mg), administered every 8 hours via 2-hour intravenous infusion 3, 4, 5
This dosing achieves the pharmacodynamic targets of 50% free time above MIC for ceftazidime and 50% free time above the 1 mg/L threshold concentration for avibactam 4, 5
Indication-Specific Dosing and Duration
Complicated Urinary Tract Infections (cUTI) Including Pyelonephritis
- Dose: 2.5 grams IV every 8 hours for 7-14 days 1, 2
- This regimen demonstrated 91% clinical cure rates in phase 3 trials for ceftazidime-resistant pathogens 6
Complicated Intra-Abdominal Infections (cIAI)
- Dose: 2.5 grams IV every 8 hours for 5-14 days 2
- Must be administered concurrently with metronidazole to provide anaerobic coverage 2
Hospital-Acquired and Ventilator-Associated Pneumonia (HABP/VABP)
- Dose: 2.5 grams IV every 8 hours for 7-14 days 2
Carbapenem-Resistant Enterobacterales (CRE) Bloodstream Infections
- Dose: 2.5 grams IV every 8 hours infused over 3 hours 1
- Duration depends on infection site and severity 2
Infusion Duration Considerations
- Standard infusion time is 2 hours 3, 5, 6
- For CRE bloodstream infections specifically, guidelines recommend 3-hour infusions 1
- Prolonged infusions may optimize time-dependent beta-lactam pharmacodynamics, particularly for high-MIC organisms 1
Critical Combination Therapy Scenarios
Metallo-β-Lactamase Producers
- Ceftazidime-avibactam is NOT effective against metallo-β-lactamases (NDM, VIM, IMP) 2
- For metallo-β-lactamase-producing CRE, combine ceftazidime-avibactam with aztreonam 1-2 grams IV every 6-8 hours 2
- This combination showed significantly lower 30-day mortality (19.2% vs 44%, P=0.007) compared to other agents 2
KPC-3 Producing Organisms
- Consider combination with a carbapenem or colistin to prevent resistance emergence 1, 2
- A "see-saw effect" can occur where ceftazidime-avibactam resistance develops but meropenem MICs decrease to susceptible range 1
Pharmacokinetic Profile in Normal Renal Function
- Ceftazidime Cmax: 88-90 mg/L; AUC: 289-291 mg·h/L; half-life: 2.76-3.27 hours 3
- Avibactam Cmax: 14.6-15.2 mg/L; AUC: 38-42 mg·h/L; half-life: 2.22-2.71 hours 3
- Both drugs demonstrate minimal protein binding (<10% for ceftazidime, 5.7-8.2% for avibactam) 3
- No appreciable accumulation occurs with every-8-hour dosing 3
Renal Elimination and Clearance
- Both ceftazidime (80-90%) and avibactam (>95%) are primarily eliminated unchanged by the kidneys 3, 7
- Ceftazidime renal clearance is approximately 100 mL/min 3
- Avibactam renal clearance is 158 mL/min, suggesting active tubular secretion in addition to glomerular filtration 3
Important Clinical Caveats
Augmented Renal Clearance
- Patients with augmented renal clearance (common in critically ill younger patients) maintain >95% target attainment with standard dosing 5
- No dose adjustment is needed despite enhanced clearance 5
Resistance Development Risk
- Prior ceftazidime-avibactam administration is a risk factor for resistance emergence in KPC-producing organisms 1, 2
- Antimicrobial susceptibility testing is recommended to guide treatment, particularly determining carbapenemase type 1, 2
Spectrum of Activity
- Effective against serine carbapenemases (KPC and OXA-48) but NOT metallo-β-lactamases 2
- The CDC recommends determining carbapenemase type before initiating treatment whenever possible 2