Recommended Dosing Regimens for Avibactam and Aztreonam
For infections caused by metallo-β-lactamase-producing carbapenem-resistant organisms, ceftazidime-avibactam combined with aztreonam is the recommended treatment regimen with significantly lower mortality rates compared to other treatment options. 1, 2
Ceftazidime-Avibactam Dosing
- Standard dosing for ceftazidime-avibactam is 2.5 g IV (2 g ceftazidime/0.5 g avibactam) every 8 hours administered as a 2-hour infusion 1, 3
- For complicated intra-abdominal infections, ceftazidime-avibactam should be given with metronidazole 500 mg IV every 6 hours 3
- Prolonged infusion (3 hours) of ceftazidime-avibactam has been associated with improved 30-day survival 1, 4
Aztreonam Dosing
- Standard aztreonam dosing is 2 g IV every 8 hours 1
- For urinary tract infections caused by gram-negative bacteria, a reduced dose of 500 mg IM once or twice daily may be sufficient 5
- Extended infusions of aztreonam may be appropriate for optimizing pharmacokinetic/pharmacodynamic parameters 1
Combination Therapy for Metallo-β-Lactamase-Producing CRE
- When used in combination with ceftazidime-avibactam for metallo-β-lactamase-producing CRE infections, aztreonam shows good in-vitro synergy as it is not hydrolyzed by metallo-β-lactamases 1, 2
- This combination has demonstrated significantly lower 30-day mortality (19.2% vs 44%) and lower clinical failure rates compared to other antimicrobial therapies 1
Duration of Therapy
- For bloodstream infections: 7-14 days 1
- For complicated urinary tract infections: 5-7 days 1, 4
- For complicated intra-abdominal infections: 5-7 days 1
- For hospital-acquired or ventilator-associated pneumonia: 10-14 days 1, 4
- Treatment should be continued for at least 48 hours after the patient becomes asymptomatic 4
Dosage Adjustments for Renal Impairment
- Both ceftazidime-avibactam and aztreonam require dosage adjustments in patients with renal impairment 6, 7
- For ceftazidime-avibactam, dose adjustment is necessary when creatinine clearance (CrCl) is ≤50 mL/min 6
- For aztreonam, dosage adjustment is necessary in patients with renal impairment, with specific adjustments based on creatinine clearance 7
Clinical Considerations
- Clinical improvement should be evident within 48-72 hours of initiating appropriate therapy 4
- The carbapenemase type produced by CRE strains should be ascertained before initiation of ceftazidime-avibactam treatment whenever possible 1
- Aztreonam has a strictly gram-negative aerobic spectrum, limiting its use as a single empiric agent 7
- When using aztreonam as monotherapy, concurrent initial therapy with other antimicrobial agents is recommended for patients at risk for gram-positive or anaerobic infections 7
Monitoring and Safety
- Emergence of ceftazidime-avibactam resistance in carbapenemase-producing K. pneumoniae has been reported, particularly with prior administration of the drug 3
- Unlike aminoglycosides, aztreonam is not nephrotoxic and has not been associated with disorders of coagulation 7
- Premature discontinuation of therapy before clinical stability is achieved should be avoided 4