Ceftazidime%2525252525252525252525252525252525252520avibactam

# Ceftazidime/avibactam ## Overview Ceftazidime/avibactam is a combination antibiotic consisting of a third-generation cephalosporin (ceftazidime) and a beta-lactamase inhibitor (avibactam). It is active against many Gram-negative bacteria, including those producing extended-spectrum beta-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs), and some oxacillinase-producing beta-lactamases (OXA-30-like carbapenemases). ## Primary Indications * Complicated intra-abdominal infections (cIAI), in combination with metronidazole. * Complicated urinary tract infections (cUTI), including pyelonephritis. * Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP). * Complicated skin and skin structure infections (cSSSI). * Treatment of infections caused by bacteria resistant to other therapies. ## Adult Dosing * **Standard Dose:** 2.5 grams (2 grams ceftazidime, 0.5 grams avibactam) administered intravenously every 8 hours. * **Duration of Therapy:** Typically 7 to 14 days, depending on the type and severity of infection, and clinical response. Local protocols may guide duration. ## Pediatric Dosing * Established dosing for pediatric patients is available for certain indications. Consult specific pediatric guidelines or prescribing information. Dosing is typically weight-based and varies by age group. * For cUTI and cIAI in patients 3 months to < 18 years: 50 mg/kg ceftazidime component (resulting in 12.5 mg/kg avibactam component) per dose IV every 8 hours. Maximum dose 2 grams ceftazidime component (0.5 grams avibactam component) per dose. * For HAP/VAP in patients 1 to < 18 years: 100 mg/kg ceftazidime component (resulting in 25 mg/kg avibactam component) per dose IV every 8 hours. Maximum dose 2 grams ceftazidime component (0.5 grams avibactam component) per dose. ## Dose Adjustments * **Renal Impairment:** Dose adjustment is required based on calculated creatinine clearance (CrCl). * CrCl ≥ 50 mL/min: No adjustment. * CrCl 30 to < 50 mL/min: 1.5 grams (1.2 grams ceftazidime, 0.3 grams avibactam) every 8 hours. * CrCl 10 to < 30 mL/min: 0.75 grams (0.6 grams ceftazidime, 0.15 grams avibactam) every 8 hours. * CrCl < 10 mL/min (including hemodialysis): 0.75 grams (0.6 grams ceftazidime, 0.15 grams avibactam) every 12 hours or with each dialysis session. * **Hepatic Impairment:** No dose adjustment needed for mild to moderate hepatic impairment. Data is limited for severe hepatic impairment. ## Contraindications * Known serious hypersensitivity to ceftazidime, avibactam, other cephalosporins, penicillins, or any component of the product. ## Adverse Effects * **Common:** Nausea, vomiting, diarrhea, headache, dizziness, constipation, abdominal pain, elevated liver enzymes (ALT, AST), rash, pruritus, insomnia, fever. * **Serious:** Severe hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with renal impairment). ## Key Drug Interactions * **Probenecid:** May increase and prolong plasma concentrations of ceftazidime. Avoid concomitant use or monitor closely. * **Valproic Acid:** Ceftazidime may reduce valproic acid concentrations, potentially leading to loss of seizure control. Monitor valproic acid levels and consider alternative antibiotics or increased valproic acid dose. ## Monitoring * Renal function (CrCl) regularly, especially in patients with known renal impairment or those at risk. * Liver function tests periodically. * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of Clostridioides difficile-associated diarrhea. * Clinical signs of infection and microbiological response. ## Clinical Pearls * Ceftazidime/avibactam is administered via intravenous infusion over 30 minutes. * When used for cIAI, it must be co-administered with metronidazole. * Consider susceptibility testing for infecting pathogens to guide therapy, especially in cases of treatment failure or suspected resistance. * Be vigilant for seizure activity, particularly in patients with reduced renal function. *** *Disclaimer: This information is intended for clinical professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and local institutional guidelines before initiating or modifying drug therapy.*