What are the indications for Avycaz (ceftazidime-avibactam)?

Indications for Avycaz (Ceftazidime-Avibactam)

Avycaz (ceftazidime-avibactam) is FDA-approved for three specific indications: 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

FDA-Approved Indications

1. Complicated Intra-Abdominal Infections (cIAI)

• Must be used in combination with metronidazole
• Effective against susceptible gram-negative microorganisms:
  • Escherichia coli
  • Klebsiella pneumoniae
  • Proteus mirabilis
  • Enterobacter cloacae
  • Klebsiella oxytoca
  • Citrobacter freundii complex
  • Pseudomonas aeruginosa
• Treatment duration: 5-14 days

2. Complicated Urinary Tract Infections (cUTI), including Pyelonephritis

• Effective against susceptible gram-negative microorganisms:
  • Escherichia coli
  • Klebsiella pneumoniae
  • Enterobacter cloacae
  • Citrobacter freundii complex
  • Proteus mirabilis
  • Pseudomonas aeruginosa
• Treatment duration: 7-14 days

3. Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia (HABP/VABP)

• Effective against susceptible gram-negative microorganisms:
  • Klebsiella pneumoniae
  • Enterobacter cloacae
  • Escherichia coli
  • Serratia marcescens
  • Proteus mirabilis
  • Pseudomonas aeruginosa
  • Haemophilus influenzae
• Treatment duration: 7-14 days

Special Considerations for Use

Role in Treating Carbapenem-Resistant Enterobacterales (CRE)

While not explicitly listed in the FDA label, Avycaz has demonstrated efficacy against certain carbapenemase-producing organisms:

• Effective against Ambler class A (KPC) and certain class D (OXA-48) carbapenemases 2
• Not effective against metallo-beta-lactamases (MBL) producers 2
• European guidelines suggest ceftazidime-avibactam for patients with severe infections due to CRE if active in vitro (conditional recommendation, low certainty of evidence) 2

Antimicrobial Stewardship Considerations

• Should be used only for infections proven or strongly suspected to be caused by susceptible bacteria 1
• Culture and susceptibility testing should guide therapy when available
• Local epidemiology and susceptibility patterns may contribute to empiric selection

Dosing Information

Adult Patients

• Standard dose: 2.5 grams (2 grams ceftazidime and 0.5 grams avibactam) IV every 8 hours
• Infusion time: 2 hours
• Renal adjustment required for CrCl ≤50 mL/min

Pediatric Patients

• Dosing varies by age and weight
• For patients 2 years to <18 years: 62.5 mg/kg up to maximum of 2.5 grams every 8 hours
• Specific dosing available for younger patients down to 31 weeks gestational age

Potential for Resistance Development

A critical concern with ceftazidime-avibactam is the potential for resistance development:

• Resistance to ceftazidime-avibactam in KPC-producing organisms has been reported 2
• Mechanisms include mutations in the KPC enzyme affecting avibactam binding 2
• Resistance can develop during treatment, occurring in approximately 3.7-8.1% of treated patients 2

Careful patient selection and appropriate use are essential to preserve the effectiveness of this important antimicrobial agent.

AI: I've provided a comprehensive overview of Avycaz indications based on the FDA label and clinical guidelines. The information is organized to clearly show the three approved indications, the specific pathogens covered, and important considerations for use.