Ceftazidime%252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (AVYCAZ) is a combination cephalosporin antibiotic and non-beta-lactam beta-lactamase inhibitor. It restores the activity of ceftazidime against many Enterobacterales and *Pseudomonas aeruginosa* resistant to standard cephalosporins, including KPC and OXA-48 carbapenemase-producing organisms. It lacks activity against metallo-beta-lactamases (e.g., NDM-1). ## Primary Indications * Complicated intra-abdominal infections (cIAI) in combination with metronidazole. * Complicated urinary tract infections (cUTI), including pyelonephritis. * Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). ## Adult Dosing Standard dose is **2.5 g (ceftazidime 2 g/avibactam 0.5 g) IV every 8 hours**. Infusion duration should be 2 hours. ## Pediatric Dosing FDA-approved for patients ≥3 months. Dosing is based on weight and indication: * **≥3 months to <18 years:** * cIAI and cUTI: 40 mg/kg (ceftazidime component) + 10 mg/kg (avibactam component) IV q8h (2-hour infusion). * Max dose: 2.5 g (2 g/0.5 g) per dose. * HABP/VABP: Dosing follows the same mg/kg per dose structure as cIAI/cUTI. ## Dose Adjustments Renal impairment requires adjustment based on CrCl (Cockcroft-Gault): * **CrCl 31–50 mL/min:** 1.25 g (1 g/0.25 g) q8h. * **CrCl 16–30 mL/min:** 0.94 g (750 mg/187.5 mg) q12h. * **CrCl 6–15 mL/min:** 0.94 g (750 mg/187.5 mg) q24h. * **CrCl ≤5 mL/min:** 0.94 g (750 mg/187.5 mg) q48h. * **End-stage renal disease (HD):** Administer dose after dialysis on dialysis days. ## Contraindications * Known severe hypersensitivity to ceftazidime, avibactam, or other beta-lactam antibiotics. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation, headache. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), and seizure (especially in patients with renal impairment who do not receive dose adjustments). ## Key Drug Interactions * **Probenecid:** Inhibits renal tubular secretion of ceftazidime; avoid co-administration as it increases serum concentrations. ## Monitoring * Renal function (baseline and during therapy). * Signs of hypersensitivity or anaphylaxis during first dose. * Neurological status (risk of neurotoxicity/seizures in renal failure). * Diarrhea/stool consistency (for *C. difficile*). ## Clinical Pearls * **Spectrum:** Does not cover *Acinetobacter baumannii* or anaerobes (hence the mandatory addition of metronidazole for intra-abdominal infections). * **Stability:** Once reconstituted, the solution must be used or discarded; refer to product labeling for specific stability windows based on storage conditions. * **Uncertainty:** Dosing for special populations (obese patients, continuous renal replacement therapy) often follows institutional protocols; consult your site’s antimicrobial stewardship team. *** **Educational Disclaimer:** This information is for educational purposes only. Clinical practice guidelines and FDA-approved labeling change frequently. Always verify specific dosing, safety, and compatibility information through the current package insert or institutional drug information resources before prescribing or administering medication.