Ceftazidime%252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (Avycaz) is a combination cephalosporin antibiotic and beta-lactamase inhibitor. Avibactam inhibits Class A, C, and some D beta-lactamases, including KPC, ESBLs, and AmpC enzymes. 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). * Off-label use for carbapenem-resistant *Enterobacterales* (CRE) and *Pseudomonas aeruginosa*. ## Adult Dosing * **Renally normal patients:** 2.5 g (ceftazidime 2 g/avibactam 0.5 g) IV every 8 hours. * **Infusion time:** Administer over 2 hours. ## Pediatric Dosing Patients 3 months to < 18 years: * **cIAI (with metronidazole) and cUTI:** Dosing is weight-based (typically 46.25 mg/kg [37 mg/kg ceftazidime / 9.25 mg/kg avibactam]) up to a maximum of 2.5 g every 8 hours. * **HABP/VABP:** 62.5 mg/kg (50 mg/kg ceftazidime / 12.5 mg/kg avibactam) every 8 hours (max 2.5 g total dose). * *Note: Consult institution-specific guidelines or pediatric dosage handbooks for exact weight-based calculations per age group.* ## Dose Adjustments Renal impairment requires dose reduction based on CrCl (mL/min): * **CrCl 31–50:** 1.25 g every 8 hours. * **CrCl 16–30:** 0.94 g (0.75 g/0.19 g) every 12 hours. * **CrCl 6–15:** 0.94 g every 24 hours. * **CrCl ≤ 5:** 0.94 g every 48 hours. * **ESRD/Hemodialysis:** Administer dose after dialysis on dialysis days. ## Contraindications * Known severe hypersensitivity to ceftazidime or avibactam. * History of severe hypersensitivity (e.g., anaphylaxis) to any other beta-lactam antibacterial agent. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation. * **Serious:** *Clostridioides difficile*-associated diarrhea, infusion-site reactions, hypersensitivity reactions. * **CNS:** Seizures (more common in patients with renal impairment who do not receive dose adjustments). ## Key Drug Interactions * **Probenecid:** May increase serum concentrations of ceftazidime; concurrent use is not recommended. * **Antagonism:** Avoid mixing in the same IV line with other antibiotics (physicochemical incompatibility). ## Monitoring * Renal function (baseline and during therapy). * Signs/symptoms of hypersensitivity. * Monitor for *C. difficile* if significant diarrhea occurs. * Neurological status (especially in patients with renal impairment). ## Clinical Pearls * **Spectrum:** Does not cover anaerobic bacteria; metronidazole must be added for cIAI. * **Extended Infusion:** The 2-hour infusion is mandatory to optimize the time above the MIC (fT > MIC). * **Stability:** Once reconstituted, the product is stable for 12 hours at room temperature or 24 hours under refrigeration. * **Uncertainty:** Effectiveness against metallo-beta-lactamases (e.g., VIM, IMP, NDM) is non-existent; empirical coverage for these pathogens requires alternate therapy (e.g., ceftazidime-avibactam + aztreonam). *** **Educational Disclaimer:** This information is for educational purposes only and does not supersede local institutional protocols or the official FDA-approved prescribing information. Always verify dosages, contraindications, and compatibility with current hospital clinical resources or clinical pharmacists prior to administration.