What is the recommended treatment regimen for complicated infections using Zavicefta (ceftazidime/avibactam)?

Zavicefta (Ceftazidime-Avibactam) Treatment Regimen for Complicated Infections

For complicated infections, Zavicefta (ceftazidime-avibactam) should be administered as 2.5 grams (2g ceftazidime/0.5g avibactam) intravenously every 8 hours as a 2-hour infusion, with treatment duration varying by infection type: 5-7 days for complicated UTIs, 5-14 days for complicated intra-abdominal infections (with metronidazole), and 7-14 days for hospital-acquired/ventilator-associated pneumonia. 1

Dosing Recommendations by Infection Type

Complicated Urinary Tract Infections (cUTI) including Pyelonephritis

• Dose: 2.5 grams (ceftazidime 2g + avibactam 0.5g) IV every 8 hours
• Infusion time: 2 hours
• Duration: 7-14 days 1
• Target pathogens: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa 1
• For carbapenem-resistant Enterobacterales (CRE): Ceftazidime-avibactam 2.5g IV q8h (weak recommendation, very low quality evidence) 2

Complicated Intra-abdominal Infections (cIAI)

• Dose: 2.5 grams (ceftazidime 2g + avibactam 0.5g) IV every 8 hours
• Concurrent therapy: Must be given with metronidazole 500mg IV every 6 hours 2, 1
• Infusion time: 2 hours
• Duration: 5-14 days 1
• Target pathogens: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa 1

Hospital-acquired Bacterial Pneumonia/Ventilator-associated Bacterial Pneumonia (HABP/VABP)

• Dose: 2.5 grams (ceftazidime 2g + avibactam 0.5g) IV every 8 hours
• Infusion time: 2 hours
• Duration: 7-14 days 1
• Target pathogens: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae 1

Bloodstream Infections (Off-label use)

• Dose: 2.5 grams (ceftazidime 2g + avibactam 0.5g) IV every 8 hours
• Duration: 7-14 days 2
• For carbapenem-resistant Enterobacterales (CRE): Ceftazidime-avibactam 2.5g IV q8h (weak recommendation, low quality evidence) 2

Dosage Adjustments for Renal Impairment

Renal function significantly impacts the dosing of Zavicefta as both ceftazidime and avibactam are primarily eliminated by the kidneys. Dose adjustment is required for patients with impaired renal function:

• CrCl >50 mL/min: Standard dosing (2.5g every 8 hours)
• CrCl 31-50 mL/min: Dose reduction required
• CrCl 16-30 mL/min: Further dose reduction required
• CrCl 6-15 mL/min: Significant dose reduction required
• ESRD on hemodialysis: Consult specific dosing guidelines

Clinical Considerations

Efficacy and Monitoring

• Clinical improvement should be seen within 48-72 hours of appropriate therapy 3
• If symptoms persist beyond 72 hours, consider:
  • Resistant organisms
  • Inadequate source control (especially for cIAI)
  • Structural abnormalities requiring intervention
  • Development of complications 3

Pharmacokinetic/Pharmacodynamic Considerations

• The approved dosage regimen achieves >95% target attainment against organisms with MICs ≤8 mg/L 4
• Avibactam extends ceftazidime's spectrum to include many ESBL, AmpC, KPC, and OXA-48 producing organisms 5
• The combination provides approximately 30% penetration into epithelial lining fluid, making it suitable for respiratory infections 6

Important Caveats

• Zavicefta is not active against metallo-β-lactamase (MBL) producing strains 5
• For complicated intra-abdominal infections, concurrent metronidazole is mandatory to cover anaerobic pathogens 1
• Emergence of resistance during therapy has been reported, particularly with prior ceftazidime-avibactam exposure 2
• No clear benefit has been demonstrated for combination therapy over monotherapy for carbapenem-resistant infections 7

Practical Application

1. Obtain appropriate cultures before initiating therapy
2. Verify susceptibility of isolates when culture results are available
3. Adjust therapy based on culture and susceptibility results
4. Ensure appropriate duration based on infection type and clinical response
5. Monitor renal function and adjust dosing accordingly

Zavicefta represents a valuable treatment option for complicated infections, particularly those caused by multidrug-resistant gram-negative pathogens, while potentially reducing carbapenem usage and preserving this important class of antibiotics.