Ceftazidime%2525252525252525252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (Avycaz) is a fixed-dose combination of a third-generation cephalosporin and a novel non-beta-lactam beta-lactamase inhibitor. It extends ceftazidime's spectrum to include Class A (ESBL, KPC), Class C (AmpC), and Class D (OXA-48) beta-lactamases. It lacks activity against metallo-beta-lactamases (e.g., NDM). ## Primary Indications * Complicated intra-abdominal infections (cIAI) in combination with metronidazole. * Complicated urinary tract infections (cUTI), including pyelonephritis. * Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). ## Adult Dosing Standard dose in patients with CrCl > 50 mL/min: 2.5 g (2 g ceftazidime/0.5 g avibactam) every 8 hours via IV infusion over 2 hours. ## Pediatric Dosing Approved for patients ≥ 3 months of age. Dosage is weight-based and administered every 8 hours (duration of 2 hours): * 3 months to < 6 months: 40 mg/kg (ceftazidime component) every 8 hours. * 6 months to < 18 years: 50 mg/kg (ceftazidime component) up to a max of 2 g every 8 hours. ## Dose Adjustments Dosing must be adjusted for renal impairment (CrCl ≤ 50 mL/min). * CrCl 31–50 mL/min: 1.25 g every 8 hours. * CrCl 16–30 mL/min: 0.94 g (0.75 g/0.19 g) every 12 hours. * CrCl 6–15 mL/min: 0.94 g every 24 hours. * CrCl ≤ 5 mL/min (including ESRD/HD): 0.94 g loading dose then 0.47 g every 48 hours. Administer post-hemodialysis. ## Contraindications * Known severe hypersensitivity to ceftazidime, avibactam, or any component of the formulation. * History of severe allergic reactions (e.g., anaphylaxis) to any beta-lactam antibiotic. ## Adverse Effects * Common: Nausea, diarrhea, constipation, vomiting. * Serious: *Clostridioides difficile*-associated diarrhea, seizures (most common in patients with renal failure receiving improper dosing), hypersensitivity reactions, elevated liver enzymes. ## Key Drug Interactions * Probenecid: May increase plasma concentrations of ceftazidime; co-administration is not recommended. * No significant CYP450 interactions, as the drug is primarily eliminated renally. ## Monitoring * Renal function (CrCl) must be assessed at baseline and monitored regularly to guide dosing adjustments. * Monitor for signs of *C. difficile* infection (persistent diarrhea). * Patients with a history of seizure disorders should be monitored closely for neurotoxicity. ## Clinical Pearls * **Spectrum:** Does *not* cover MRSA, *Acinetobacter baumannii*, or anaerobes (hence, metronidazole is required for intra-abdominal indications). * **Stability:** Once reconstituted, the solution is stable for 12 hours at room temperature and 24 hours under refrigeration. * **Efficacy:** Superior outcomes in KPC-producing organisms compared to older therapies (e.g., polymyxins or carbapenems). * **Dosing protocol:** Exact dosing in specific pediatric sub-populations or patients on CRRT may vary based on local institutional protocols; consult your facility's ID pharmacist or antimicrobial stewardship team. *** *Educational Disclaimer: This information is for educational purposes only. Drug dosing, contraindications, and guidelines change frequently. Always consult the most recent package insert, internal institutional protocols, and clinical pharmacology databases (e.g., Lexicomp, Micromedex) before prescribing or administering medication.*