Ceftazidime-Avibactam and Aztreonam Dosing for Adults
Ceftazidime-Avibactam Standard Dosing
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
Indication-Specific Dosing and Duration
Complicated intra-abdominal infections (cIAI): 2.5 grams IV every 8 hours for 5-14 days, must be given concurrently with metronidazole 500 mg IV every 8 hours to provide anaerobic coverage 2, 1
Complicated urinary tract infections (cUTI) including pyelonephritis: 2.5 grams IV every 8 hours for 7-14 days 2, 3, 1
Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP): 2.5 grams IV every 8 hours for 7-14 days 2, 1
Carbapenem-resistant Enterobacterales (CRE) infections: 2.5 grams IV every 8 hours, with duration dependent on infection site and severity 3
Critical Combination Therapy Consideration
For metallo-β-lactamase-producing CRE, ceftazidime-avibactam combined with aztreonam is recommended, showing significantly lower 30-day mortality (19.2% vs 44%, P=0.007) compared to other antimicrobial agents. 3 This combination is necessary because ceftazidime-avibactam is not effective against metallo-β-lactamases but aztreonam is, while avibactam protects aztreonam from other β-lactamases.
Aztreonam Standard Dosing
The standard adult dose of aztreonam is 1-2 grams IV every 6-8 hours. 4
Specific Clinical Contexts
Gram-negative enteric bacilli infections: Aztreonam 1-2 grams every 6-8 hours, typically combined with an aminoglycoside (gentamicin, tobramycin, or amikacin depending on susceptibility) 4
When combined with ceftazidime-avibactam for metallo-β-lactamase producers: Standard dosing of 1-2 grams every 6-8 hours is appropriate, though specific combination dosing protocols may vary by institution 3
Renal Dose Adjustments
Dose adjustments are required for both agents when creatinine clearance is ≤50 mL/min. 1, 5 The FDA label specifies that ceftazidime-avibactam requires reductions in both dose quantity and/or administration interval for patients with renal impairment, though specific adjusted doses should follow manufacturer guidelines based on exact creatinine clearance values 1.
Important Clinical Caveats
Resistance Development Risk
Emergence of ceftazidime-avibactam resistance has been reported in carbapenemase-producing K. pneumoniae, particularly with prior drug administration and mutations in the bla KPC-3 gene. 2, 3
For KPC-3 producing organisms, combination therapy with a carbapenem or colistin may be considered to prevent resistance development 3
Carbapenemase Type Matters
The CDC recommends determining the carbapenemase type and/or ceftazidime-avibactam susceptibility before initiating treatment whenever possible. 3
Ceftazidime-avibactam is effective against serine carbapenemases (KPC and OXA-48) but not against metallo-β-lactamases (NDM, VIM, IMP), which require the addition of aztreonam 3
Monotherapy vs Combination
For most E. coli infections sensitive to ceftazidime-avibactam, monotherapy is appropriate except for cIAI requiring anaerobic coverage with metronidazole 2
Evidence for combination therapy in carbapenem-resistant Enterobacterales is insufficient, though some experts suggest potential benefit in severe pneumonia 2