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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 bacteria, including those producing certain extended-spectrum beta-lactamases (ESBLs), carbapenemases (e.g., KPC, OXA-48-like), and AmpC beta-lactamases.
## Primary Indications
* Complicated intra-abdominal infections (cIAI) in combination with metronidazole.
* Complicated urinary tract infections (cUTI), including pyelonephritis.
* Nosocomial pneumonia, including ventilator-associated pneumonia (VAP).
These indications are typically reserved for situations where treatment options are limited due to resistance.
## Adult Dosing
The standard dose for cIAI, cUTI, and nosocomial pneumonia is **2.5 grams every 8 hours (given as aztreonam 2 grams and avibactam 0.5 grams)** administered by intravenous infusion over 30 minutes. For cIAI, it must be co-administered with metronidazole.
## Pediatric Dosing
Dosing in pediatric patients varies by indication, age, and weight. Specific protocols and guidelines should be consulted.
* **Complicated UTI/cIAI:**
* **3 months to < 6 months:** 90 mg/kg/dose of aztreonam component (equivalent to 112.5 mg/kg/dose of the combination) IV every 8 hours.
* **6 months to < 2 years:** 40 mg/kg/dose of aztreonam component (equivalent to 50 mg/kg/dose of the combination) IV every 8 hours.
* **2 years to < 12 years:** 50 mg/kg/dose of aztreonam component (equivalent to 62.5 mg/kg/dose of the combination) IV every 8 hours.
* **12 years to < 18 years:** 1.5 grams (aztreonam 1.2 g/avibactam 0.3 g) IV every 8 hours.
* **Hospital-acquired/Ventilator-associated bacterial pneumonia (HABP/VAP):**
* **3 months to < 6 months:** 90 mg/kg/dose of aztreonam component (equivalent to 112.5 mg/kg/dose of the combination) IV every 6 hours.
* **6 months to < 2 years:** 60 mg/kg/dose of aztreonam component (equivalent to 75 mg/kg/dose of the combination) IV every 6 hours.
* **2 years to < 12 years:** 75 mg/kg/dose of aztreonam component (equivalent to 93.75 mg/kg/dose of the combination) IV every 6 hours.
* **12 years to < 18 years:** 2.5 grams (aztreonam 2 g/avibactam 0.5 g) IV every 8 hours.
Dosing should not exceed the maximum dose for adults.
## Dose Adjustments
* **Renal Impairment (Adults):**
* **CrCl ≥ 60 mL/min:** No adjustment needed.
* **CrCl 30 to < 60 mL/min:** 1.5 grams (aztreonam 1.2 g/avibactam 0.3 g) every 8 hours.
* **CrCl 15 to < 30 mL/min:** 1 gram (aztreonam 0.8 g/avibactam 0.2 g) every 8 hours.
* **CrCl < 15 mL/min:** 0.75 grams (aztreonam 0.6 g/avibactam 0.15 g) every 8 hours.
* **Hemodialysis:** Dose administered post-dialysis; consult specific guidelines.
* **Hepatic Impairment (Adults):** No dose adjustment is generally required.
## Contraindications
* Known severe hypersensitivity to aztreonam, avibactam, or any component of the formulation.
* Known severe hypersensitivity to penicillins or cephalosporins may increase the risk of hypersensitivity reactions.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, headache, fever, phlebitis, local infusion site reactions, and elevated liver enzymes. Serious adverse effects include hypersensitivity reactions (including anaphylaxis) and Clostridioides difficile-associated diarrhea.
## Key Drug Interactions
* **Probenecid:** May increase plasma concentrations of aztreonam.
* **Valproic acid:** Aztreonam may decrease valproic acid levels. Monitor valproic acid concentrations.
## Monitoring
* **Renal function:** Monitor for changes, especially in patients with pre-existing renal impairment or those receiving other nephrotoxic agents.
* **Liver function:** Monitor for elevated liver enzymes.
* **Signs of hypersensitivity:** Monitor closely during and after infusion.
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
* **Microbiological cultures:** Obtain appropriate specimens for culture and susceptibility testing prior to initiating therapy.
## Clinical Pearls
* Aztreonam/avibactam is primarily active against aerobic Gram-negative bacteria; it lacks activity against most Gram-positive and anaerobic bacteria. Therefore, combination with metronidazole is required for cIAI.
* Prior to initiating therapy, assess for previous hypersensitivity reactions to beta-lactams.
* Infuse over 30 minutes.
* Consider the potential for cross-reactivity with penicillin or cephalosporin allergies, though the risk is generally considered lower with monobactams.
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**Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the most current prescribing information for definitive guidance and to adapt treatment based on individual patient factors and local institutional protocols.
