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# Aztreonam/Avibactam (Avycaz)
## Overview
Aztreonam/avibactam is a combination antibiotic. Aztreonam is a monobactam beta-lactam antibiotic that inhibits bacterial cell wall synthesis. Avibactam is a beta-lactamase inhibitor that protects aztreonam from degradation by certain beta-lactamase enzymes. This combination is active against many Gram-negative aerobic bacteria, including those resistant to other beta-lactam antibiotics due to production of certain beta-lactamases.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated urinary tract infections (cUTI)
* Complicated intra-abdominal infections and complicated urinary tract infections, in patients 18 years and older, when caused by or suspected to be caused by infections eligible for treatment based on the following cases:
* Caused or suspected to be caused by Gram-negative aerobic bacteria:
* Carbapenem-resistant Enterobacteriaceae (CRE)
* *Pseudomonas aeruginosa* (multidrug-resistant)
* *Acinetobacter baumannii*-calcoaceticus complex (multidrug-resistant)
* Other Gram-negative aerobic bacteria susceptible to aztreonam.
## Adult Dosing
The recommended dosage for adults is **2.5 grams** (2 grams aztreonam and 1 gram avibactam) administered intravenously over 3 hours every 8 hours for 7 to 14 days.
* **cIAI:** Consider adding metronidazole for anaerobic coverage.
* **cUTI:** 1.5 grams (1 gram aztreonam and 0.5 gram avibactam) administered intravenously over 3 hours every 8 hours for 7 to 10 days.
## Pediatric Dosing
Dosing in pediatric patients (1 month to less than 18 years of age) is **weight-based** and depends on the indication and severity of infection. Consult specific pediatric guidelines or the product insert for precise dosing which typically ranges from **50 mg/kg to 125 mg/kg of aztreonam component every 6 to 8 hours**, with avibactam component dosed proportionally. Maximum doses should not be exceeded.
## Dose Adjustments
* **Renal Impairment (CrCl < 30 mL/min):**
* **2.5 g regimen:** Reduce to 1.25 grams every 8 hours.
* **1.5 g regimen:** Reduce to 0.75 grams every 8 hours.
* **Hemodialysis:** Administer dose after hemodialysis on dialysis days. Dosage reduction as above for CrCl < 30 mL/min is recommended. The need for additional doses on hemodialysis days should be based on the patient's CrCl.
* **Hepatic Impairment:** No dosage adjustment is required for mild to moderate hepatic impairment. Data is limited 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, constipation, rash, pruritus, infusion site reactions, fever, headache, and elevated liver enzymes (ALT, AST). Serious adverse effects can include hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, and seizures.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of aztreonam, potentially increasing the risk of adverse effects. Avoid co-administration.
* **Valproic Acid:** Concomitant use may decrease serum valproic acid concentrations, potentially leading to loss of seizure control. Monitor valproic acid levels and consider alternative agents if needed.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (ALT, AST, bilirubin)
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea
* Therapeutic drug monitoring of valproic acid if co-administered.
## Clinical Pearls
* This combination is particularly useful for infections caused by multidrug-resistant Gram-negative organisms, including those producing ESBLs, AmpC, and some carbapenemases (e.g., KPC, OXA-48-like).
* Aztreonam is typically stable in the presence of serine beta-lactamases but is hydrolyzed by metallo-beta-lactamases (MBLs); avibactam inhibits MBLs. However, aztreonam is still susceptible to hydrolysis by some carbapenemases (e.g., NDM-1).
* Not active against Gram-positive bacteria or anaerobes.
* For cIAI, combination with an agent with anaerobic activity (e.g., metronidazole) is generally recommended.
* Ensure appropriate dose adjustments are made for renal impairment.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the current prescribing information approved by regulatory agencies and your institution's guidelines for complete and up-to-date drug information before making clinical decisions.
