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# Ceftazidime-avibactam
## Overview
Ceftazidime-avibactam is a combination cephalosporin antibiotic and non-beta-lactam beta-lactamase inhibitor. It extends the spectrum of ceftazidime to include many multidrug-resistant Gram-negative pathogens, including *Pseudomonas aeruginosa* and carbapenem-resistant Enterobacterales (CRE) producing KPC or OXA-48 carbapenemases.
## 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
* **cUTI/cIAI:** 2.5 g (ceftazidime 2 g/avibactam 0.5 g) IV every 8 hours.
* **HABP/VABP:** 2.5 g IV every 8 hours.
* **Duration:** 7–14 days depending on infection severity and source.
## Pediatric Dosing
* **Patients ≥ 3 months:** Dosing is weight-based.
* **< 20 kg:** 50 mg/kg (ceftazidime component) every 8 hours (duration of infusion 2 hours).
* **20 to < 70 kg:** 37.5 mg/kg (ceftazidime component) every 8 hours (duration of infusion 2 hours).
* **≥ 70 kg:** 2.5 g (ceftazidime 2 g/avibactam 0.5 g) every 8 hours (duration of infusion 2 hours).
* *Note: Always consult institutional protocols for neonatal/pediatric dosing regimens.*
## Dose Adjustments
* **Renal Impairment:** Dosage must be adjusted based on creatinine clearance (CrCl). If CrCl ≤ 50 mL/min, the dose and/or frequency must be reduced.
* **End-stage Renal Disease (ESRD):** Supplemental dosing is required following hemodialysis.
* **Hepatic Impairment:** No dosage adjustment indicated.
## Contraindications
* Known severe hypersensitivity to ceftazidime, avibactam, or any cephalosporin.
* History of severe hypersensitivity reactions (e.g., anaphylaxis) to any other beta-lactam antibiotic.
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, abdominal pain, fever, constipation.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), seizures (particularly in patients with renal impairment who do not receive dose adjustments), and hypersensitivity reactions.
## Key Drug Interactions
* **Probenecid:** May inhibit the renal tubular secretion of ceftazidime, increasing plasma concentrations; co-administration is generally not recommended.
## Monitoring
* **Renal Function:** Monitor serum creatinine and calculate CrCl frequently, especially in patients with fluctuating renal status to avoid neurotoxicity (seizures).
* **Clinical Response:** Monitor for signs of therapeutic efficacy.
* **Safety:** Monitor for symptoms of CDAD (watery/bloody stools) and signs of hypersensitivity.
## Clinical Pearls
* **Spectrum:** It is inactive against anaerobic bacteria; it must be paired with metronidazole for intra-abdominal infections to cover anaerobes.
* **Spectrum Gap:** It does **not** cover *Acinetobacter baumannii* and has limited activity against metallo-beta-lactamase (e.g., NDM) producing organisms.
* **Infusion Time:** Standard infusion time is 2 hours; this is critical for pediatric dosing and recommended per current guidelines to optimize pharmacodynamics.
* **Neurotoxicity:** Ceftazidime has a dose-dependent risk of neurotoxicity (encephalopathy, confusion, tremor, seizures), particularly in patients with baseline renal impairment or those receiving excessive doses.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice guidelines vary by institution and region. Always verify dosages, contraindications, and compatibility with the latest FDA-approved prescribing information, your hospital’s antimicrobial stewardship program, or a current drug monograph before administration.
