Ceftazidime%252525252525252525252520avibactam

# 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 is specifically designed to provide robust activity against multidrug-resistant Gram-negative pathogens, including *Pseudomonas aeruginosa* and carbapenem-resistant *Enterobacterales* (CRE) that produce KPC or OXA-48 beta-lactamases. It does **not** cover 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 and ventilator-associated bacterial pneumonia (HABP/VABP). ## Adult Dosing Standard dosing for patients with CrCl >50 mL/min: * **cIAI/cUTI:** 2.5 g (ceftazidime 2 g/avibactam 0.5 g) IV every 8 hours. * **HABP/VABP:** 2.5 g IV every 8 hours. * **Infusion time:** Administer over 2 hours for all indications. ## Pediatric Dosing Patients 3 months and older: * Dosing is weight-based (typically determined by total body weight in patients ≤ 40 kg). * *Note: Always consult institutional protocols or the most recent package insert, as pediatric dosing is highly weight-stratified.* * Common regimen: 50 mg/kg (ceftazidime) + 12.5 mg/kg (avibactam) IV every 8 hours, infused over 2 hours. Maximum dose is 2.5 g. ## Dose Adjustments Renal impairment requires dose titration based on estimated CrCl (Cockcroft-Gault): * **CrCl 31–50 mL/min:** 1.25 g IV every 8 hours. * **CrCl 16–30 mL/min:** 0.94 g (ceftazidime 0.75 g/avibactam 0.1875 g) IV every 12 hours. * **CrCl 6–15 mL/min:** 0.94 g IV every 24 hours. * **CrCl ≤ 5 mL/min (or ESRD):** 0.94 g IV every 48 hours. * **Hemodialysis:** Administer dose after dialysis on dialysis days. ## Contraindications * Known severe hypersensitivity to any component or other cephalosporins. * History of severe anaphylactic reactions to penicillins or other beta-lactams. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation, headache. * **Serious:** *Clostridioides difficile*-associated diarrhea, infusion-site reactions. * **Neurological:** Risk of seizures and encephalopathy, particularly in patients with renal impairment who receive doses exceeding their clearance capacity. ## Key Drug Interactions * **Probenecid:** May increase serum concentrations of ceftazidime by inhibiting renal tubular secretion. ## Monitoring * **Renal Function:** Monitor CrCl throughout therapy to adjust doses appropriately. * **CNS Monitoring:** Observe for signs of neurotoxicity, especially in elderly or renally-impaired patients. * **Microbiology:** Monitor clinical response and repeat cultures to ensure adequate source control and susceptibility. ## Clinical Pearls * **Source Control:** For cIAI, concomitant metronidazole (typically 500 mg every 8h) is **required** to cover anaerobic organisms. * **Spectrum:** It is highly effective against MDR *Pseudomonas* but has no activity against anaerobic organisms on its own. * **Stability:** Once reconstituted, the solution must be used promptly or refrigerated; consult product literature for specific stability timelines. * **Dosing Uncertainty:** Dosing in continuous renal replacement therapy (CRRT) or high-flux hemodialysis is not standardized; consult infectious disease pharmacy/nephrology for site-specific protocols. *** **Educational Disclaimer:** This information is for educational purposes only. Clinical practice guidelines and local formulary protocols change frequently. Always verify the most current prescribing information via the FDA label or institutional clinical decision support tools before prescribing or administering medication.