Ceftazidime%2525252525252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam (Avycaz) is a fixed-dose combination of a third-generation cephalosporin and a non-beta-lactam beta-lactamase inhibitor. It effectively targets multidrug-resistant Gram-negative pathogens, including *Pseudomonas aeruginosa* and carbapenem-resistant Enterobacterales (CRE), by inhibiting Class A, C, and some D beta-lactamases (specifically KPC and OXA-48). ## Primary Indications * Complicated intra-abdominal infections (cIAI) in combination 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**. * **Infusion time:** Administer over 2 hours. * **Duration:** 7 to 14 days depending on infection site and severity. ## Pediatric Dosing Patients $\geq$ 3 months of age: * **3 months to < 6 months:** 25 mg/kg (ceftazidime component) every 8 hours. * **6 months to < 18 years:** Dosing is weight-based (typically 40–50 mg/kg of ceftazidime component) up to a maximum of 2 g ceftazidime/0.5 g avibactam per dose. Refer to institutional pediatric protocols for precise mg/kg calculations based on indication. ## Dose Adjustments **Renal Impairment:** Requires adjustment based on estimated CrCl (Cockcroft-Gault). * **CrCl 31–50 mL/min:** 1.25 g every 8 hours. * **CrCl 16–30 mL/min:** 0.94 g (ceftazidime 0.75 g / avibactam 0.1875 g) every 12 hours. * **CrCl 6–15 mL/min:** 0.94 g every 24 hours. * **CrCl $\leq$ 5 mL/min:** 0.94 g every 48 hours. * **Hemodialysis:** Administer dose after dialysis on dialysis days. ## Contraindications * Known severe hypersensitivity (e.g., anaphylaxis) to ceftazidime, avibactam, or other beta-lactam antibiotics. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, headache, increased ALT/AST. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions, seizures (primarily in patients with impaired renal function receiving excessive doses), and hemolytic anemia. ## Key Drug Interactions * **Probenecid:** May increase ceftazidime plasma concentrations by inhibiting renal excretion; avoid concomitant use. * **Contraceptives:** May decrease the efficacy of estrogen-containing oral contraceptives due to alteration of gut flora. ## Monitoring * **Renal Function:** Monitor CrCl closely; adjust dose promptly if function declines. * **Clinical Efficacy:** Monitor for improvement in symptoms of infection. * **Neurological:** Monitor for signs of neurotoxicity (seizures, confusion) if renal dosing is inaccurate. * **Safety:** Monitor for signs of allergic reaction or emergence of *C. difficile* diarrhea. ## Clinical Pearls * **Spectrum:** Does not cover *Acinetobacter baumannii* or most anaerobes; always add metronidazole for cIAI. * **Administration:** The extended 2-hour infusion time is critical to optimize time above the minimum inhibitory concentration (T > MIC). * **Resistance:** While potent against KPC-producing organisms, it is not active against metallo-beta-lactamases (e.g., NDM, VIM). * **Compatibility:** Do not mix with other drugs in the same IV line unless compatibility data are confirmed. *** **Educational Disclaimer:** This information is for educational purposes only. Clinical guidelines and local antibiograms vary significantly. Always verify current prescribing information, institutional formulary requirements, and patient-specific factors with a clinical pharmacist or the latest official product monograph before prescribing or administering medication.