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# Aztreonam-avibactam (Avycaz)
## Overview
Aztreonam-avibactam is a combination parenteral antibiotic. Aztreonam is a monobactam beta-lactam antibiotic. Avibactam is a beta-lactamase inhibitor that protects aztreonam from degradation by certain beta-lactamases, including extended-spectrum beta-lactamases (ESBLs), Klebsiella pneumoniae carbapenemases (KPCs), and some metallo-beta-lactamases (e.g., OXA-48-like). This combination is active against many Gram-negative bacteria, including those with certain highly resistant mechanisms.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated urinary tract infections (cUTI), including pyelonephritis
* Nosocomial pneumonia, including ventilator-associated pneumonia (VPA)
Use should be guided by susceptibility testing.
## Adult Dosing
The recommended dose for adults is **2.5 grams** (2 grams aztreonam and 0.5 grams avibactam) administered intravenously over **3 hours** every **6 hours**.
* **cIAI and cUTI:** Treat for 5 to 14 days.
* **Nosocomial pneumonia/VAP:** Treat for 7 to 14 days.
Duration of therapy depends on the site and severity of infection and pathogen susceptibility.
## Pediatric Dosing
Established pediatric dosing varies based on age, weight, indication, and renal function. Consult specific pediatric guidelines or the product insert for detailed recommendations.
* **For complicated UTI/cIAI in patients aged 3 months to <2 years:** Doses ranging from 30 mg/kg of aztreonam component up to 120 mg/kg total dose (based on aztreonam component) every 6 hours have been studied.
* **For complicated UTI/cIAI in patients aged 2 to <18 years:** Doses ranging from 30 mg/kg of aztreonam component up to 120 mg/kg total dose (based on aztreonam component) every 6 hours, with a maximum dose of 2.5 grams, have been studied.
* **For nosocomial pneumonia/VAP in patients aged 6 months to <18 years:** Doses ranging from 30 mg/kg of aztreonam component up to 120 mg/kg total dose (based on aztreonam component) every 6 hours, with a maximum dose of 2.5 grams, have been studied.
## Dose Adjustments
Dose adjustments are required for **renal impairment**.
* **CrCl 30-49 mL/min:** 1.5 grams IV every 8 hours.
* **CrCl 10-29 mL/min:** 1.5 grams IV every 12 hours.
* **CrCl <10 mL/min or ESRD/hemodialysis:** 1 gram IV every 12 hours. For patients on hemodialysis, administer after hemodialysis.
Dosing in hepatic impairment is generally not required.
## Contraindications
* Hypersensitivity to aztreonam, avibactam, or any component of the formulation.
* Specific contraindication for patients with a known history of severe allergic reaction to penicillins, cephalosporins, or other beta-lactam antibiotics, though cross-reactivity is generally considered low for aztreonam.
## Adverse Effects
Common adverse effects include:
* Nausea, vomiting, diarrhea
* Headache
* Elevated liver enzymes (AST, ALT)
* Hypokalemia
* Rash, pruritus
* Injection site reactions
Serious adverse effects:
* Hypersensitivity reactions (anaphylaxis)
* Clostridioides difficile-associated diarrhea
* Seizures (rarely, particularly in patients with renal impairment)
* Hepatotoxicity
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of aztreonam. Monitor for increased aztreonam-related adverse effects.
* **Valproic acid:** Cases of decreased valproic acid concentrations have been reported with concurrent use of carbapenems. While not definitively established for aztreonam-avibactam, cautious monitoring of valproic acid levels may be warranted.
## Monitoring
* Renal function (especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents).
* Liver function tests (baseline and periodically).
* Electrolytes (particularly potassium).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Clinical signs and symptoms of infection; evaluate for improvement.
* For patients receiving antiepileptic drugs like valproic acid, monitor drug levels.
## Clinical Pearls
* Gram-negative bacterial coverage is broad, but activity against some metallo-beta-lactamases (MBLs) is limited. Susceptibility testing is crucial.
* The aztreonam component is generally stable in the presence of serine beta-lactamases.
* Administer by IV infusion over **3 hours**; rapid infusion has been associated with adverse events.
* Consider the risk of hypersensitivity reactions, especially in patients with a history of allergies.
* The possibility of C. difficile-associated diarrhea should be considered in all patients with diarrhea during or after treatment.
This information is intended for healthcare professionals and does not replace comprehensive prescribing information. Always verify current prescribing information and consult with a qualified healthcare provider before making any treatment decisions.
