Ceftazidime%252525252525252525252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (AVYCAZ) is a combination cephalosporin antibiotic and non-beta-lactam beta-lactamase inhibitor. It extends the spectrum of ceftazidime to include most Class A (KPC), Class C (AmpC), and some Class D (OXA-48) carbapenemases, as well as extended-spectrum beta-lactamases (ESBLs). It is ineffective against metallo-beta-lactamases (e.g., NDM). ## Primary Indications * Complicated intra-abdominal infections (cIAI) in conjunction with metronidazole. * Complicated urinary tract infections (cUTI), including pyelonephritis. * Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). ## Adult Dosing Standard dose is **2.5 g (ceftazidime 2 g / avibactam 0.5 g) IV every 8 hours**. Infusion duration is 2 hours. * **cIAI/cUTI:** Typically 5 to 14 days. * **HABP/VABP:** 7 to 14 days. ## Pediatric Dosing Approved for patients **3 months of age and older**. Dosing is weight-based (calculated as total amount of ceftazidime/avibactam): * **3 months to <6 months:** 40/10 mg/kg IV every 8 hours. * **6 months to <18 years (<50 kg):** 50/12.5 mg/kg IV every 8 hours (Max 2.5 g). * **≥50 kg:** Use adult dosing (2.5 g IV every 8 hours). ## Dose Adjustments Dose adjustments are required for renal impairment (CrCl ≤50 mL/min). Calculation based on Cockcroft-Gault: * **CrCl 31–50 mL/min:** 1.25 g IV every 8 hours. * **CrCl 16–30 mL/min:** 0.94 g (0.75 g ceftazidime/0.1875 g avibactam) IV every 12 hours. * **CrCl 6–15 mL/min:** 0.94 g IV every 24 hours. * **CrCl ≤5 mL/min:** 0.94 g IV every 48 hours. * *Hemodialysis:* Administer dose after dialysis on dialysis days. ## Contraindications * Known severe hypersensitivity to ceftazidime, avibactam, or any component of the formulation. * History of severe hypersensitivity (e.g., anaphylaxis) to other beta-lactam antibiotics. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation. * **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions, seizures (primarily in patients with renal impairment receiving inappropriate doses), and infusion site reactions. ## Key Drug Interactions * **Probenecid:** Inhibits renal tubular secretion of ceftazidime, significantly increasing serum concentrations. Co-administration is not recommended. ## Monitoring * Renal function (baseline and during therapy, especially if status changes). * Signs/symptoms of anaphylaxis during first dose. * Monitor for secondary infections or persistent diarrhea (consider *C. difficile*). ## Clinical Pearls * **Spectrum:** Specifically valuable for MDR Gram-negative organisms, including *Pseudomonas aeruginosa* and *Klebsiella pneumoniae* Carbapenemase (KPC) producers. * **Metronidazole Addition:** In cIAI, metronidazole must be added to cover anaerobic organisms, as ceftazidime-avibactam has no anaerobic activity. * **Stability:** Once reconstituted, the solution must be used or refrigerated promptly. Follow specific institutional protocols regarding dilution and shelf-life post-reconstitution. * **Uncertainty:** Dosing for continuous renal replacement therapy (CRRT) or high-flux hemodialysis is not standardized; consult institutional pharmacist or infectious disease specialist for customized regimens. *** **Educational Disclaimer:** This information is for educational purposes and does not substitute for clinical judgment. Prescribing and dosing should always be verified against the most current FDA-approved labeling, institutional formulary guidelines, and patient-specific factors.