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# Aztreonam-avibactam (Avycaz)
## Overview
Aztreonam-avibactam is a combination antibiotic consisting of aztreonam, a monobactam antibiotic, and avibactam, a beta-lactamase inhibitor. This combination is active against many Gram-negative aerobic bacteria, including those with resistance mechanisms like extended-spectrum beta-lactamases (ESBLs), ceftazidime-resistant *Enterobacteriaceae* (CRE), *Pseudomonas aeruginosa*, and *Acinetobacter baumannii*.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated urinary tract infections (cUTI), including pyelonephritis
* Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP)
* Treatment of infections caused by problematic Gram-negative aerobic organisms such as *Pseudomonas aeruginosa* with limited or no susceptible agents.
## Adult Dosing
The recommended dose for adults is 2.5 grams (aztreonam 2 grams and avibactam 0.5 grams) administered intravenously every 8 hours. Aztreonam is typically administered as a continuous infusion over 3 hours (total daily dose 7.5 grams), while avibactam is administered as a 30-minute IV infusion. However, many institutions administer both as a continuous infusion of aztreonam 2g/avibactam 0.5g every 8 hours. Refer to local protocols for specific administration recommendations.
## Pediatric Dosing
Dosing for pediatric patients depends on age, weight, and indication.
* **cIAI, cUTI, HABP/VABP:**
* 25 kg to <40 kg: 63 mg/kg aztreonam and 15.75 mg/kg avibactam intravenously every 8 hours as a 3-hour continuous infusion.
* ≥40 kg: 2 grams aztreonam and 0.5 grams avibactam intravenously every 8 hours as a 3-hour continuous infusion.
* For patients weighing >50 kg, the adult dose of 2.5 grams (2g aztreonam/0.5g avibactam) may be used.
* **Gram-negative infections with limited susceptibility:**
* 25 kg to <40 kg: 80 mg/kg aztreonam and 20 mg/kg avibactam intravenously every 8 hours as a 3-hour continuous infusion (maximum of 2 grams aztreonam and 0.5 grams avibactam per dose).
* ≥40 kg: 2 grams aztreonam and 0.5 grams avibactam intravenously every 8 hours as a 3-hour continuous infusion.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 30 mL/min: No adjustment needed.
* CrCl < 30 mL/min: Adjust dose based on local protocols and CrCl. Generally, a dose reduction is recommended, with extended intervals. For example, a common recommendation for CrCl 15-29 mL/min is 1.5 grams (1.2g aztreonam/0.3g avibactam) every 12 hours or extended infusion. Consult prescribing information for detailed guidance.
* **Hepatic Impairment:** No dose adjustment is typically required for patients with 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 diarrhea, nausea, vomiting, injection site reactions, rash, fever, headache, and elevated liver enzymes. Serious adverse effects include hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, and seizures (more common with aztreonam alone in patients with predisposing factors, but possible with the combination).
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of aztreonam.
* **Valproic acid/Divalproex sodium:** Aztreonam has been associated with a reduction in valproic acid serum concentrations, leading to reduced efficacy. Monitor valproic acid levels and consider alternative antibiotics if clinical failure occurs.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions and *Clostridioides difficile*-associated diarrhea.
* Monitor renal function, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* Monitor liver function tests.
* If concomitant valproic acid is used, monitor its serum levels closely.
## Clinical Pearls
* Aztreonam-avibactam is primarily active against aerobic Gram-negative bacteria. It has no activity against anaerobic bacteria.
* The beta-lactamase inhibitor avibactam protects aztreonam from degradation by many clavulanic acid-resistant beta-lactamases, including certain class A and class C beta-lactamases.
* Consider combination therapy with an anti-anaerobic agent when anaerobic organisms are suspected.
* Ensure adequate renal and hepatic function assessment before and during therapy.
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*Please verify the current prescribing information for the most up-to-date details on dosing, administration, contraindications, adverse effects, and drug interactions. This information is intended for educational purposes and does not substitute for professional medical judgment.*
