Ceftazidime%25252525252525252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (AVYCAZ) is a combination cephalosporin antibiotic and non-beta-lactam beta-lactamase inhibitor. Avibactam expands the spectrum of ceftazidime to include many Class A (KPC), Class C (AmpC), and Class D (OXA-48) carbapenemases. It lacks activity against metallo-beta-lactamases (e.g., NDM). ## Primary Indications * Complicated intra-abdominal infections (cIAI) (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. * **cIAI:** 2.5 g q8h for 5–14 days (with metronidazole). * **cUTI:** 2.5 g q8h for 7–14 days. * **HABP/VABP:** 2.5 g q8h for 7–14 days. Infusions should be administered over 2 hours. ## Pediatric Dosing FDA-approved for patients ≥3 months of age for cIAI, cUTI, and HABP/VABP: * **3 months to <6 months:** 40 mg/kg (ceftazidime component) q8h. * **6 months to <18 years:** Dosing is weight-based (typically 40–50 mg/kg ceftazidime component) q8h, capped at 2.5 g. * *Note: Always consult institutional pediatric protocols or specialized references (e.g., Harriet Lane) for exact mg/kg calculations based on indication and age.* ## Dose Adjustments **Renal Impairment:** Requires dose reduction 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 (0.75 g/0.1875 g) q12h. * **CrCl 6–15 mL/min:** 0.94 g q24h. * **CrCl ≤5 mL/min:** 0.94 g q48h. * **End-stage renal disease (HD):** Administer after dialysis on hemodialysis days. ## Contraindications * Known severe hypersensitivity to ceftazidime-avibactam, ceftazidime, or avibactam. * History of severe allergic reactions (e.g., anaphylaxis) to any other cephalosporin or beta-lactam agent due to potential cross-reactivity. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions, seizures (primarily in patients with renal impairment receiving excessive doses). * **Labs:** Increased ALT/AST, positive direct Coombs test (risk of hemolytic anemia). ## Key Drug Interactions * **Probenecid:** Inhibits renal tubular secretion of ceftazidime; avoid concomitant use. * No significant CYP450 interactions, as it is primarily renally cleared. ## Monitoring * **Renal function:** Monitor CrCl throughout therapy to ensure appropriate dose adjustments. * **Clinical response:** Monitor for resolution of symptoms and signs of infection. * **Neurological status:** Monitor if using high doses, especially in patients with impaired renal function, for CNS toxicity. * **Signs of colitis:** Monitor for diarrhea indicating *C. difficile*. ## Clinical Pearls * **Spectrum:** It is a "last-resort" agent for MDR Gram-negative infections, specifically carbapenem-resistant Enterobacterales and *Pseudomonas aeruginosa*. * **MBL Inactivity:** It is ineffective against metallo-beta-lactamases; if NDM-producing organisms are suspected or confirmed, this drug is not indicated. * **Infusion Time:** The 2-hour infusion is critical for maintaining time above MIC (T > MIC) targets, particularly for multidrug-resistant pathogens. * **Coombs Test:** May cause a false-positive direct Coombs test; note this on the patient record to avoid confusion in blood bank cross-matching. *** **Disclaimer:** This information is intended for educational purposes only. Always consult the most recent institutional guidelines, hospital formulary, and the official FDA-approved prescribing information (package insert) before prescribing or administering any medication. Clinical judgment should prevail in individual patient management.