Approved Indications for Ceftazidime-Avibactam
Ceftazidime-avibactam (AVYCAZ) is FDA-approved for the treatment of complicated intra-abdominal infections (in combination with metronidazole), complicated urinary tract infections including pyelonephritis, and hospital-acquired/ventilator-associated bacterial pneumonia in adult and pediatric patients (at least 31 weeks gestational age). 1
Specific FDA-Approved Indications
1. Complicated Intra-abdominal Infections (cIAI)
- Approved for use in combination with metronidazole for treatment of cIAI caused by susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa 1
- Treatment duration: 5-14 days 1
2. Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
- Indicated for treatment of cUTI including pyelonephritis caused by susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa 1
- Treatment duration: 7-14 days 1
3. Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)
- Approved for treatment of HABP/VABP caused by susceptible gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae 1
- Treatment duration: 7-14 days 1
Clinical Applications in Resistant Infections
Ceftazidime-avibactam has particular utility in treating infections caused by multidrug-resistant gram-negative bacteria:
Recommended for treatment of carbapenem-resistant Enterobacterales (CRE) infections, including:
Effective against difficult-to-treat Pseudomonas aeruginosa (DTR-PA) infections (2.5 g IV q8h) 2
Antimicrobial Spectrum
Ceftazidime-avibactam is active against:
- Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales 3
- AmpC-producing Enterobacterales 3
- Klebsiella pneumoniae carbapenemase (KPC)-producing organisms 2, 3
- OXA-48-producing Enterobacterales 2, 3
- Drug-resistant Pseudomonas aeruginosa 3
Important limitation: Not active against metallo-β-lactamase (MBL)-producing strains 2, 3
Dosing Considerations
Adult Patients (CrCl >50 mL/min)
- Standard dose: 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours by intravenous infusion over 2 hours 1
Pediatric Patients
- Dosing varies by age, with appropriate weight-based dosing for patients from 31 weeks gestational age and older 1
- For ages 2 years to <18 years: 62.5 mg/kg to maximum of 2.5 grams every 8 hours 1
Renal Adjustment
- Dosage adjustment required for adult patients with CrCl <50 mL/min and pediatric patients aged 2 years and older with renal impairment 1
Clinical Efficacy
- Demonstrated non-inferiority to carbapenems in pivotal phase III trials for cUTI, cIAI, and HABP/VABP 3
- Particularly valuable as a carbapenem-sparing option for treating ceftazidime-resistant Enterobacterales and Pseudomonas aeruginosa infections 4
- In the REPRISE trial, showed similar clinical cure rates (91%) compared to best available therapy (primarily carbapenems) in patients with ceftazidime-resistant pathogens 4
Important Considerations and Caveats
- Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported, particularly with prior ceftazidime-avibactam exposure 2
- When treating KPC-3 producers, combination therapy with ceftazidime-avibactam plus a carbapenem or colistin may be considered due to potential resistance development 2
- Should be used only for proven or strongly suspected infections caused by susceptible bacteria to reduce the development of drug-resistant bacteria 1
Ceftazidime-avibactam represents an important therapeutic option for serious infections caused by resistant gram-negative pathogens, particularly as a carbapenem-sparing alternative in appropriate clinical scenarios.