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# Aztreonam-avibactam (Avycaz)
## Overview
Aztreonam-avibactam is an intravenous combination of aztreonam, a monobactam antibiotic, and avibactam, a beta-lactamase inhibitor. It is active against many Gram-negative bacteria, including those resistant to other beta-lactam antibiotics due to the production of certain beta-lactamases.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated urinary tract infections (cUTI), including pyelonephritis
* Nosocomial pneumonia, including ventilator-associated pneumonia (VAP)
* *Note: Generally reserved for situations where there are limited or no alternative treatment options due to resistance.*
## Adult Dosing
* **Standard Dose:** 2.5 grams (aztreonam 2 grams and avibactam 0.5 grams) administered intravenously every 8 hours.
* **Duration:** Typically 7 to 14 days, depending on the site of infection and clinical response.
* **Maximum Dose:** Not explicitly defined beyond the standard dose.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and patient age/weight. Refer to specific pediatric guidelines or FDA-approved labeling for exact regimens. Examples:
* **cIAI/cUTI:** 50 mg/kg (aztreonam component) with 12.5 mg/kg (avibactam component) per dose every 8 hours. Do not exceed the adult dose of 2.5 grams per dose.
* **Nosocomial Pneumonia/VAP:** 25 mg/kg (aztreonam component) with 6.25 mg/kg (avibactam component) per dose every 8 hours. Do not exceed the adult dose of 2.5 grams per dose.
* *Note: Dosing for pediatric patients weighing >120kg should usually not exceed the adult dose.*
## Dose Adjustments
* **Renal Impairment:**
* CrCl $\ge$ 60 mL/min: No dose adjustment.
* CrCl 30 to $<60$ mL/min: 1.5 grams (aztreonam 1.2 grams and avibactam 0.3 grams) every 8 hours.
* CrCl 15 to $<30$ mL/min: 1 gram (aztreonam 0.8 grams and avibactam 0.2 grams) every 8 hours.
* CrCl $<15$ mL/min or End-Stage Renal Disease (including hemodialysis): 0.75 grams (aztreonam 0.6 grams and avibactam 0.15 grams) every 12 hours. Administer immediately after hemodialysis if patient is on HD.
* **Hepatic Impairment:** No dose adjustment recommended for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment.
## Contraindications
* Known hypersensitivity to aztreonam, avibactam, or any component of the formulation.
## Adverse Effects
Common adverse effects include nausea, vomiting, diarrhea, headache, phlebitis or infusion site reactions, rash, elevated liver enzymes (AST, ALT), and hypersensitivity reactions.
## Key Drug Interactions
* **Probenecid:** May increase plasma concentrations of aztreonam; monitor for potential toxicity.
* **Valproic Acid:** May decrease valproic acid concentrations leading to loss of seizure control.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests.
* Signs and symptoms of hypersensitivity reactions.
* Clinical signs of infection and resolution of symptoms.
* For patients on hemodialysis, dosing timing relative to dialysis.
## Clinical Pearls
* Aztreonam is generally well-tolerated by patients with penicillin allergies.
* Avibactam inhibits a broad range of beta-lactamases, including some Extended-Spectrum Beta-Lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs), and some oxacillinases (OXAs). It does *not* inhibit metallo-$\beta$-lactamases (e.g., NDM).
* Susceptibility testing is crucial, especially for organisms with multiple resistance mechanisms.
* Administered as a 30-minute intravenous infusion.
* Reconstitute according to manufacturer instructions; further dilution is required before infusion.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information or a reliable drug compendium for complete details and potential updates.*
