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# Aztreonam-Avibactam
## Overview
Aztreonam-avibactam is a fixed-dose combination of a monobactam antibiotic and a non-beta-lactam beta-lactamase inhibitor. It is specifically designed to overcome resistance mediated by metallo-beta-lactamases (MBLs), such as NDM-1, which are typically resistant to most other beta-lactam/beta-lactamase inhibitor combinations.
## Primary Indications
Treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible Gram-negative organisms, particularly when MBL-producing organisms are suspected or confirmed.
## Adult Dosing
* **Standard dose:** 500 mg (aztreonam) / 1373 mg (avibactam) administered intravenously every 8 hours.
* **Infusion time:** Administer over 2 hours.
## Pediatric Dosing
Safety and efficacy in pediatric patients have not been fully established. Use in this population is generally off-label or restricted to compassionate use programs. Decisions should be guided by institutional infectious disease specialists and pediatric pharmacology.
## Dose Adjustments
* **Renal Impairment:** Requires dose adjustment based on estimated creatinine clearance (CrCl). If CrCl ≤ 50 mL/min, the dosing interval or dose must be reduced. Specific calculators per institutional protocols or product manufacturer prescribing information (e.g., Vabomere/Avycaz guidance equivalents) are required, as dosing thresholds vary by site.
* **Hepatic Impairment:** No specific adjustments currently recommended, but use with caution.
## Contraindications
* Known hypersensitivity to aztreonam or avibactam.
* History of severe hypersensitivity (e.g., anaphylaxis) to any other beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, dizziness, and constipation.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), and elevation in liver transaminases.
## Key Drug Interactions
* **Probenecid:** May increase serum concentrations of aztreonam; co-administration is generally not recommended.
* **Synergy:** Often used in combination with other agents (e.g., ceftazidime-avibactam) to provide "double-coverage" against multi-drug resistant organisms, though these combinations should be vetted by clinical microbiology and pharmacy.
## Monitoring
* **Renal function:** Monitor serum creatinine and adjust dosing if renal function declines.
* **Signs/Symptoms of Infection:** Monitor for clinical improvement or signs of superinfection.
* **Gastrointestinal:** Monitor for persistent or severe diarrhea (screen for *C. difficile*).
## Clinical Pearls
* **MBL Activity:** Unlike other beta-lactamase inhibitors, avibactam does not inhibit MBLs; however, aztreonam is unique among beta-lactams because it is stable against hydrolysis by MBLs. Adding avibactam protects the aztreonam from degradation by other co-produced beta-lactamases (like ESBLs, KPCs, and AmpC enzymes).
* **Not a Carbapenem:** Aztreonam-avibactam is safe to use in patients with a history of penicillin or cephalosporin allergy (with the exception of ceftazidime-avibactam cross-reactivity).
* **Therapeutic Drug Monitoring (TDM):** Where available, TDM may be considered in complex patients, renal replacement therapy (RRT), or high-volume distribution states to ensure target attainment (fT>MIC).
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practice varies by institution. Always verify current prescribing information, dose-adjustment protocols, and local antimicrobial stewardship guidelines before prescribing or administering medication.
