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# Aztreonam/Avibactam (Avycaz)
## Overview
Aztreonam/avibactam is a combination of a beta-lactamase-resistant monobactam antibiotic and a beta-lactamase inhibitor. It is active against many Gram-negative bacteria, including those with extended-spectrum beta-lactamases (ESBLs), carbapenemases (e.g., KPC, OXA-48-like), and some metallo-beta-lactamases (e.g., NDM).
## Primary Indications
* Complicated urinary tract infections (cUTI), including pyelonephritis.
* Complicated intra-abdominal infections (cIAI), in combination with metronidazole.
* Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), caused by susceptible Gram-negative organisms.
## Adult Dosing
* **cUTI, cIAI, HAP/VAP:** 2.5 grams (2 grams aztreonam/0.5 grams avibactam) intravenously every 8 hours.
* **Duration:** Typically 7-14 days, depending on infection site, severity, and pathogen.
## Pediatric Dosing
Dosing in pediatric patients is variable and should be determined based on specific guidelines and local protocols. Generally, doses range from 15 mg/kg aztreonam component to 60 mg/kg aztreonam component every 8 hours, adjusted for renal function and infection severity. Refer to institutional guidelines or PDR for precise dosing.
## Dose Adjustments
**Renal Impairment (CrCl):**
* **CrCl ≥ 50 mL/min:** No adjustment needed.
* **CrCl 30 to < 50 mL/min:** 1.5 grams (1.2 grams aztreonam/0.3 grams avibactam) IV every 8 hours.
* **CrCl 10 to < 30 mL/min:** 1 gram (0.8 grams aztreonam/0.2 grams avibactam) IV every 12 hours.
* **CrCl < 10 mL/min (and ESRD/hemodialysis):** 1 gram (0.8 grams aztreonam/0.2 grams avibactam) IV every 24 hours. Administer after hemodialysis on hemodialysis days.
**Hepatic Impairment:** No specific dose adjustment is typically recommended for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment.
## Contraindications
* Known hypersensitivity to aztreonam, avibactam, or any component of the formulation.
* Patients with a history of IgE-mediated hypersensitivity reactions to penicillins or cephalosporins may have an increased risk of cross-reactivity.
## Adverse Effects
* **Common:** Elevated liver enzymes (AST, ALT), nausea, vomiting, diarrhea, constipation, headache, fever, rash, infusion site reactions.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially in renal impairment), hepatic failure.
## Key Drug Interactions
* **Aminoglycosides:** Can have synergistic activity against some Gram-negative bacteria, but concurrent administration may increase nephrotoxicity/ototoxicity risk.
* **Probenecid:** May increase aztreonam serum concentrations.
* **Warfarin:** Monitor INR closely.
* **Vaccines:** Live bacterial vaccines may be less effective.
## Monitoring
* **Renal function:** Essential for dose adjustment.
* **Liver function tests:** Monitor for signs of hepatotoxicity.
* **Signs and symptoms of infection:** Clinical response.
* **Microbiological cultures and sensitivities:** To confirm susceptible pathogens and assess treatment efficacy.
* **INR/PT:** If on warfarin.
## Clinical Pearls
* Aztreonam is resistant to most serine beta-lactamases, including ESBLs, KPCs, and OXA-48-like carbapenemases. Avibactam inhibits these enzymes, restoring aztreonam activity.
* Due to aztreonam's monobactam structure, it typically does not cause cross-reactivity in patients with penicillin or cephalosporin allergies, making it a valuable option in such cases. However, caution is still advised. Monitor for hypersensitivity reactions.
* For cIAI, aztreonam/avibactam must be used in combination with metronidazole to cover anaerobic organisms.
* Ensure adequate hydration and appropriate dose adjustments in patients with renal impairment.
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*This information is intended for clinical professionals. Always consult the official prescribing information and institutional protocols for the most current and complete details before prescribing.*
