Ceftazidime-Avibactam

Aka: Ceftazidime-Avibactam, Zavicefta, Avycaz

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II. Indications

  1. See Third Generation Anti-Pseudomonal Cephalosporin
  2. Conditions
    1. Gram-Negative, Multi-drug resistant intraabdominal Infections and Urinary Tract Infections
      1. No anaerobic coverage (add Metronidazole for abdominal infections)
    2. Pseudomonas infections
      1. Pseudomonas Osteochondritis
      2. Cystic Fibrosis lung infection
      3. Ventilator-Associated Pneumonia
  3. Ceftazidime Bacterial Coverage
    1. Pseudomonas aeruginosa (Main indication)
    2. EKP Gram Negative Bacteria (Escherichia coli, Klebsiella, Proteus)
    3. ESP Gram Negative Bacteria (Enterobacter, Serratia, Providencia)
    4. Also covers Citrobacter species
    5. Gram Positive Cocci poorly covered
    6. No Gram Negative Coccobacilli coverage
  4. Avibactam additional activity
    1. Addition of Beta-Lactamase inhibitor (Avibactam) circumvents Beta-Lactamase resistance

III. Pharmacokinetics

  1. Half-Life Ceftazidime: 2.7 hours (similar for Avibactam)
  2. Ceftazidime is excreted in urine (80-90% unchanged, avibactam is 100% unchanged on excretion)
  3. Adjust dose in Renal Failure

IV. Medications

  1. Avycaz 2.5 g
    1. Ceftazidime 2 g
    2. Avibactam 0.5 g

V. Dosing: Adult

  1. GIve 2.5 g IV every 8 hours (infused over 2 hours)
  2. Duration
    1. Urinary Tract Infections: Treat for 7 to 14 days
    2. Intraabdominal infections: Treat for 5 to 14 days
      1. Combine with Metronidazole
  3. Renal Dosing
    1. eGFR 31 to 50 ml/min
      1. Give 1.25 g IV every 8 hours
    2. eGFR 16 to 30 ml/min
      1. Give 0.94 g IV every 12 hours
    3. eGFR 6 to 15 ml/min
      1. Give 0.94 g IV every 24 hours
    4. eGFR <5 ml/min
      1. Load 0.94 g IV every 48 hours (after Hemodialysis)

VI. Dosing: Child

  1. Age 6 months to 18 years
    1. GIve 62.5 mg/kg (max 2.5 g) IV every 8 hours (infused over 2 hours)
  2. Age 3 to 6 months
    1. GIve 50 mg/kg IV every 8 hours (infused over 2 hours)
  3. Renal Dosing
    1. eGFR 31 to 50 ml/min
      1. Give 31.25 mg/kg (max 1.25 g) IV every 8 hours
    2. eGFR 16 to 30 ml/min
      1. Give 23.75 mg/kg (max 0.94 g) IV every 12 hours
    3. eGFR 6 to 15 ml/min
      1. Give 23.75 mg/kg (max 0.94 g) IV every 24 hours
    4. eGFR <5 ml/min
      1. Give 23.75 mg/kg (max 0.94 g) IV every 48 hours (after Hemodialysis)

VII. Safety

  1. Avoid Avibactam in pregnancy (adverse effects in pregnancy)
  2. Unknown safety in Lactation
    1. Ceftazidime is excreted in Breast Milk

VIII. Efficacy

  1. Limited spectrum (focused Gram Negative bacillus and Pseudomonas coverage)

IX. Adverse Effects

  1. Gastrointestinal (Nausea, Vomiting, Diarrhea, Constipation)
  2. Dizziness
  3. Anxiousness
  4. Abdominal Pain
  5. Paresthesias

X. Resources

  1. Ceftazidime-Avibactam (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d9c2803f-dc9c-4b19-b4a3-8303bc8c15fd

XI. References

  1. Morrison and LoVecchio (2021) Crit Dec Emerg Med 35(1): 28
  2. Matesanz (2021) Rev Esp Quimioter 34 Suppl 1(Suppl1):38-40 +PMID: 34598423 [PubMed]

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