Indications and Usage of Ceftazidime-Avibactam
Ceftazidime-avibactam 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 adults and pediatric patients (at least 31 weeks gestational age). 1
Primary Indications
1. Complicated Intra-abdominal Infections (cIAI)
- Must be used in combination with metronidazole 500 mg IV every 8 hours in adults 1
- Pediatric patients require metronidazole 10 mg/kg IV every 8 hours 1
- Recommended treatment duration: 5-14 days 1
2. Complicated Urinary Tract Infections (cUTI)
- Including pyelonephritis
- Monotherapy is sufficient (no need for additional antimicrobials) 1
- Recommended treatment duration: 7-14 days 1
- Particularly effective for CRE-UTI with a weak recommendation based on very low quality evidence 2
3. Hospital-acquired Bacterial Pneumonia/Ventilator-associated Bacterial Pneumonia (HABP/VABP)
Specific Pathogen Coverage
Ceftazidime-avibactam is particularly valuable for treating infections caused by:
Carbapenem-resistant Enterobacterales (CRE) 2
- Effective against KPC-producing strains (Klebsiella pneumoniae carbapenemase)
- Effective against OXA-48-producing strains
- Standard dose: 2.5 g IV q8h (2 g ceftazidime + 0.5 g avibactam) 2
Multidrug-resistant Pseudomonas aeruginosa 3, 4
- Including isolates resistant to carbapenems, piperacillin-tazobactam, or ceftazidime
Extended-spectrum β-lactamase (ESBL)-producing organisms 4
- Highly active against ESBL-positive E. coli and K. pneumoniae
Important Limitations
- Not effective against metallo-β-lactamase (MBL) producers (e.g., NDM-1) when used alone 3
- For MBL-producing CRE, combination with aztreonam is suggested 2
- Not recommended for tigecycline-resistant bloodstream infections 2
Dosing Considerations
Adult Dosing
- Standard dose: 2.5 g (2 g ceftazidime + 0.5 g avibactam) IV every 8 hours as a 2-hour infusion 1
- Extended infusion (3 hours) may improve outcomes in critically ill patients 5
Renal Adjustment (Adults)
- CrCl >50 mL/min: 2.5 g IV q8h
- CrCl 31-50 mL/min: 1.25 g IV q8h
- CrCl 16-30 mL/min: 0.94 g IV q12h
- CrCl 6-15 mL/min: 0.94 g IV q24h
- CrCl ≤5 mL/min: 0.94 g IV q48h 5, 1
Pediatric Dosing
- Age-based dosing ranges from 25 mg/kg for neonates to 62.5 mg/kg (maximum 2.5 g) for older children 1
- Renal adjustment is required for pediatric patients aged 2 years and older with impaired renal function 1
Clinical Efficacy and Outcomes
- Clinical cure rates of approximately 91% for ceftazidime-resistant infections, comparable to best available therapy (primarily carbapenems) 6
- May reduce mortality by 182 per 1000 patients treated in CRE infections compared to other antimicrobials (RR 0.55,95% CI 0.42-0.72) 2
- Potential for reduced treatment failure (RR 0.49,95% CI 0.34-0.70) 2
- Lower risk of acute kidney injury compared to alternatives like colistin 2
Antimicrobial Stewardship Considerations
- Should be reserved for confirmed or strongly suspected infections caused by resistant pathogens 1
- When possible, determine carbapenemase type before initiating therapy for CRE infections 2
- Consider as an alternative to carbapenems to reduce carbapenem use and slow resistance development 7
Monitoring and Resistance Concerns
- Emergence of resistance during therapy has been reported in KPC-producing K. pneumoniae 2
- Risk factors for resistance development include prior ceftazidime-avibactam exposure 2
- A "see-saw effect" may occur where ceftazidime-avibactam resistance develops but carbapenem susceptibility returns 2
- Consider combination with a carbapenem when treating KPC-3 producers to prevent resistance 2, 5
Ceftazidime-avibactam represents a valuable treatment option for serious multidrug-resistant gram-negative infections, particularly when carbapenems are not effective or appropriate.