Ceftazidime%2525252525252520avibactam

# Ceftazidime-avibactam ## Overview Ceftazidime-avibactam is a combination cephalosporin antibacterial and beta-lactamase inhibitor. Avibactam inhibits Class A (ESBL, KPC), Class C (AmpC), and some Class D beta-lactamases, restoring the activity of ceftazidime against many multidrug-resistant Gram-negative organisms. ## 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 dose is **2.5 g (ceftazidime 2 g/avibactam 0.5 g) IV every 8 hours** infused over 2 hours. * **Duration:** 7 to 14 days, depending on severity and site of infection. ## Pediatric Dosing FDA-approved for patients aged 3 months and older: * **3 months to < 6 months:** 40 mg/kg (ceftazidime) / 10 mg/kg (avibactam) IV q8h. * **6 months to < 18 years:** Dosing is weight-based (typically 50 mg/kg/12.5 mg/kg) but capped at the adult dose. Consult institutional protocols or pediatric handbooks (e.g., Harriet Lane) for specific age-based weight bands. * **Infusion time:** 2 hours. ## Dose Adjustments Requires adjustment for renal impairment (CrCl ≤ 50 mL/min). * **CrCl 31–50 mL/min:** 1.25 g every 8 hours. * **CrCl 16–30 mL/min:** 0.94 g (ceftazidime 0.75 g/avibactam 0.187 g) every 12 hours. * **ESRD/Hemodialysis:** 0.94 g loading dose, followed by 0.94 g every 48 hours. Administer after dialysis on dialysis days. * *Note: Always verify renal function utilizing the Cockcroft-Gault equation or institutional preference.* ## Contraindications * Known severe hypersensitivity to ceftazidime, avibactam, or other beta-lactams. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, constipation, headache. * **Serious:** *Clostridioides difficile*-associated diarrhea, seizures (higher risk in renal impairment if dose not adjusted), positive direct Coombs test (hemolytic anemia risk). ## Key Drug Interactions * **Probenecid:** Inhibits renal tubular secretion of ceftazidime; avoid concurrent use. * **Bacteriostatic agents:** Potential antagonistic effect if used with certain antibiotics (clinical significance is typically low). ## Monitoring * **Renal function:** Monitor CrCl closely to adjust dosing. * **Neurological status:** Monitor for signs of CNS toxicity (seizures, confusion) especially in elderly or renally-impaired patients. * **Hematologic:** Monitor for signs of hemolytic anemia (rare). * **Clinical response:** Monitor for resolution of inflammatory markers and clinical symptoms. ## Clinical Pearls * **Spectrum:** Active against *Pseudomonas aeruginosa* (including MDR strains) and carbapenem-resistant Enterobacteriaceae (CRE). It is *not* active against anaerobes; always add metronidazole for cIAI. * **Infusion:** Standard 2-hour infusion is mandatory for efficacy and to maintain drug concentrations above the MIC threshold. * **Resistance:** Avibactam does not provide coverage for metallo-beta-lactamases (e.g., NDM-1). Consider susceptibility profiles if regional resistance patterns vary. *** **Educational Disclaimer:** This information is for educational purposes only. Clinical practice is subject to change. Always verify current, institution-specific guidelines, prescribing information, and patient-specific factors before administering any medication.