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# 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 Class D (OXA-48) beta-lactamases. It is notably active against *Pseudomonas aeruginosa* and carbapenem-resistant Enterobacterales (CRE).
## 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 is **2.5 g (2 g ceftazidime/0.5 g avibactam) IV every 8 hours**. Infusions should be administered over 2 hours.
## Pediatric Dosing
Approved for patients $\ge$ 3 months of age. Dosage is calculated based on weight:
* **3 months to < 18 years:** 40 mg/kg (ceftazidime component) + 10 mg/kg (avibactam component) IV every 8 hours.
* **Maximum dose:** 2.5 g (2 g/0.5 g) every 8 hours.
## Dose Adjustments
Requires dose reduction based on estimated CrCl (Cockcroft-Gault for adults).
* **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 (0.75 g/0.1875 g) q24h.
* **CrCl $\le$ 5 mL/min:** 0.94 g (0.75 g/0.1875 g) q48h.
* **End-stage renal disease (HD):** Administer dose after dialysis on dialysis days.
## Contraindications
* Known severe hypersensitivity to ceftazidime, avibactam, or other beta-lactams.
* History of severe hypersensitivity (e.g., anaphylaxis, SJS/TEN) to any cephalosporin.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, constipation, headache.
* **Serious:** *Clostridioides difficile*-associated diarrhea, seizures (especially in renal impairment).
* **Other:** Increased ALT/AST, infusion site reactions.
## Key Drug Interactions
* **Probenecid:** Inhibits renal secretion of ceftazidime; avoid concomitant use.
* **General:** No clinically significant cytochrome P450 interactions, as it is primarily renally cleared.
## Monitoring
* **Renal Function:** Monitor CrCl frequently and adjust dose accordingly.
* **Neurological:** Monitor for signs of neurotoxicity (seizures, confusion) in patients with baseline renal impairment.
* **Laboratory:** CBC (for leukopenia/neutropenia) and LFTs if therapy duration exceeds 14 days.
## Clinical Pearls
* **Spectrum:** Does not cover metallo-beta-lactamases (e.g., NDM-1) or *Acinetobacter baumannii*.
* **Infusion Time:** Must be administered over 2 hours; do not administer as a bolus to prevent potential neurotoxicity.
* **Empiric Use:** Should be reserved for infections proven or highly suspected to be caused by carbapenem-resistant Gram-negative pathogens. Local antibiograms and institutional guidelines should dictate precise utilization.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice is subject to change. Always verify current prescribing information in a reliable drug reference (e.g., Lexicomp, Micromedex) or institutional policy before prescribing or administering any medication.
