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# Aztreonam-avibactam (Avycaz)
## Overview
Aztreonam-avibactam is a combination antibiotic consisting of aztreonam, a monobactam beta-lactam antibiotic, and avibactam, a beta-lactamase inhibitor. It is active against Gram-negative aerobic bacteria, including many resistant strains producing extended-spectrum beta-lactamases (ESBLs), carbapenemases (e.g., KPC, OXA-48-like, VIM, IMP), and certain metallo-beta-lactamases (e.g., NDM).
## Primary Indications
* Complicated intra-abdominal infections (cIAI) - typically in combination with metronidazole.
* Complicated urinary tract infections (cUTI), including pyelonephritis.
* Complicated intra-abdominal infections (cIAI)
* Pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)
## Adult Dosing
**Complicated Intra-abdominal Infections (cIAI), Complicated Urinary Tract Infections (cUTI), and Pneumonia:**
* **Dose:** 2.5 grams (aztreonam 2 grams / avibactam 0.5 grams) administered intravenously every 8 hours.
* **Duration:** Typically 5 to 14 days, depending on the indication and severity. For cUTI, durations can range from 7 to 10 days. For cIAI, typically 5 to 14 days. For HAP/VAP, typically 7 days.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and depends on the indication:
* **cUTI and cIAI (3 months to <18 years):**
* **Dose:** 125 mg/kg aztreonam component (effective dose of 150 mg/kg aztreonam component if considering avibactam ratio) IV every 8 hours.
* **Maximum dose:** 2 grams aztreonam component (2.5 grams total for combination) every 8 hours.
* **Duration:** 7 to 14 days.
* **Complicated Intra-abdominal Infections, Hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HAP/VAP) (3 months to <18 years):**
* **Dose:** 125 mg/kg combined aztreonam/avibactam IV every 8 hours.
* **Maximum dose:** 2 grams aztreonam component (2.5 grams total for combination) every 8 hours.
* **Duration:** 7 to 14 days.
*Note: Pediatric dosing requires careful calculation with strict adherence to weight-based recommendations and maximum dosages. Avibactam component is generally dosed in a 4:1 ratio with aztreonam; therefore, a 2g aztreonam dose results in a 0.5g avibactam dose.*
## Dose Adjustments
* **Renal Impairment:**
* CrCl 30 to <90 mL/min: No dose adjustment needed but monitor closely for efficacy.
* CrCl <30 mL/min: Reduce the dose to 1.25 grams (aztreonam 1 gram / avibactam 0.25 grams) IV every 8 hours.
* Hemodialysis: No dose adjustment for aztreonam-avibactam. Administer dose after dialysis.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known hypersensitivity to aztreonam, avibactam, or any component of the formulation.
* Patients with known hypersensitivity to penicillins or cephalosporins may also be at risk for cross-reactivity, though caution, not absolute contraindication.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, headache, dizziness, infusion-related reactions (phlebitis, pain).
Less common: Rash, urticaria, elevated liver enzymes (AST, ALT), hypokalemia.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions including anaphylaxis, seizures (particularly in patients with renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of aztreonam.
* **Live bacterial vaccines:** May decrease the efficacy of live vaccines.
## Monitoring
* **Renal function:** Closely monitor in patients with or at risk for renal impairment.
* **Liver function tests:** Monitor for elevations.
* **Signs and symptoms of hypersensitivity reactions.**
* **Signs and symptoms of *Clostridioides difficile*-associated diarrhea.**
* **Clinical signs of infection:** Monitor for improvement in signs and symptoms of infection.
* **Culture and susceptibility results:** Adjust therapy as needed based on susceptibility data.
## Clinical Pearls
* Aztreonam-avibactam offers a valuable option for treating infections caused by multidrug-resistant Gram-negative organisms.
* For cIAI, it should be administered in combination with metronidazole to cover anaerobic pathogens.
* The aztreonam component is typically not hydrolyzed by many common beta-lactamases, and avibactam inhibits a broad spectrum of serine beta-lactamases. However, aztreonam is susceptible to hydrolysis by metallo-beta-lactamases (e.g., NDM), although avibactam can offer some protection against certain metallo-beta-lactamases. Specific susceptibility testing is essential.
* Dosing adjustments are crucial for patients with significant renal impairment.
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**Disclaimer:** This information is intended for healthcare professionals. Please consult the most current official prescribing information and relevant clinical guidelines for complete details, including contraindications, warnings, precautions, and adverse reactions, before making any therapeutic decisions. Dosing and duration may vary based on institutional protocols and individual patient factors.
