Ceftazidime-Avibactam Dosing Recommendations
The standard adult dose of ceftazidime-avibactam is 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered intravenously every 8 hours over 2 hours in patients with creatinine clearance greater than 50 mL/min. 1
Adult Dosing by Indication
Standard dosing applies across all approved indications:
Complicated intra-abdominal infections (cIAI): 2.5 g IV every 8 hours over 2 hours for 5-14 days, must be given concurrently with metronidazole 500 mg IV every 6-8 hours for anaerobic coverage 2, 3, 1
Complicated urinary tract infections (cUTI) including pyelonephritis: 2.5 g IV every 8 hours over 2 hours for 7-14 days 2, 3, 1
Hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP): 2.5 g IV every 8 hours over 2 hours for 7-14 days 2, 1
Carbapenem-resistant Enterobacterales (CRE) bloodstream infections: 2.5 g IV every 8 hours over 2 hours for 7-14 days 3
The 2.5 g dose represents a fixed 4:1 ratio of ceftazidime to avibactam that maintains complementary pharmacokinetic profiles, as both drugs have similar half-lives of approximately 2 hours and are primarily renally cleared 4, 5.
Pediatric Dosing
Weight-based dosing is required for all pediatric patients:
Age 2 to <18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV every 8 hours, maximum dose 2.5 grams 6, 3, 1
Age 6 months to <2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV every 8 hours 1
Age 3 to <6 months: 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) IV every 8 hours 6, 1
Age >28 days to <3 months: 37.5 mg/kg (ceftazidime 30 mg/kg and avibactam 7.5 mg/kg) IV every 8 hours 1
Age ≤28 days with gestational age ≥31 weeks: 25 mg/kg (ceftazidime 20 mg/kg and avibactam 5 mg/kg) IV every 8 hours 1
For pediatric cIAI, metronidazole 10 mg/kg IV every 8 hours must be given concurrently 1.
Renal Impairment Dosing
Dose reduction is mandatory for moderate to severe renal impairment to prevent drug accumulation and neurotoxicity: 7
CrCl >50 mL/min: Standard dose of 2.5 g IV every 8 hours 7, 1
CrCl 31-50 mL/min: Reduced dose required per FDA labeling 7
CrCl ≤30 mL/min: Further dose reduction required per FDA labeling 7
Hemodialysis patients: Administer after hemodialysis, as approximately 55% of avibactam is removed during a 4-hour dialysis session 7, 8
The linear relationship between avibactam clearance and creatinine clearance parallels that of ceftazidime, allowing maintenance of the 4:1 ratio across all renal function levels 8, 4.
Critical Administration Details
Infusion duration matters for optimal pharmacodynamics:
For severe infections in patients with normal or augmented renal clearance, extending infusion to 3-4 hours may be necessary to achieve higher PK/PD targets (100% fT>MIC) 9
Continuous infusion at higher dosages may be required for the most severe infections to achieve 100% fT≥4×MIC targets 9
Safety Monitoring
Monitor for neurotoxicity, particularly in renal impairment:
Beta-lactam accumulation can cause seizures, encephalopathy, and confusion 7
Ceftazidime has lower pro-convulsive activity than some other beta-lactams, but vigilance remains essential 7
Most common adverse events are gastrointestinal disorders (13% with ceftazidime-avibactam) 10
Resistance Considerations
Emergence of resistance has been reported, particularly with prior ceftazidime-avibactam exposure:
Mutations in bla KPC-3 gene are a key resistance mechanism in carbapenemase-producing K. pneumoniae 2
For most E. coli infections, monotherapy is appropriate except for cIAI requiring anaerobic coverage 2
Evidence for combination therapy in CRE infections is insufficient, though some suggest potential benefit in severe pneumonia 2