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# Aztreonam / Avibactam (AVYCAZ)
## Overview
- Combination antibiotic: aztreonam (monobactam) + avibactam (β-lactamase inhibitor)
- Avibactam protects aztreonam from degradation by extended-spectrum β-lactamases (ESBLs), KPC, and OXA-48 carbapenemases
- Aztreonam retains activity against metallo-β-lactamase (MBL)-producing organisms (e.g., NDM, VIM) but avibactam does not protect against MBLs; the combination is primarily used for infections due to MBL-producers when aztreonam alone is co-administered with avibactam
## Primary Indications
- Complicated intra-abdominal infections (cIAI) (in combination with metronidazole)
- Hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP)
- Complicated urinary tract infections (cUTI), including pyelonephritis
- Infections caused by carbapenem-resistant Enterobacterales (CRE) producing ESBLs, KPC, OXA-48 (not MBL)
- Off-label: Used with ceftazidime-avibactam (or high-dose aztreonam alone) for MBL-producing infections; local protocols vary
## Adult Dosing
- **cUTI, cIAI, HABP/VABP (FDA-approved):** Aztreonam 3 g / avibactam 1.5 g IV over 3 hours every 8 hours
- **Dosing in infections due to CRE (including MBL producers with avibactam co-administration):** Same 3 g / 1.5 g every 8 hours; duration based on infection site and clinical response
- **Renal impairment:** CrCl 31–50 mL/min: 2.25 g (aztreonam 1.5 g / avibactam 0.75 g) IV every 8 hours; CrCl 16–30 mL/min: 2.25 g IV every 12 hours; CrCl ≤15 mL/min or hemodialysis: 1.5 g (aztreonam 1 g / avibactam 0.5 g) IV every 12 hours (give after HD on dialysis days)
## Pediatric Dosing
- **Not FDA-approved for children <18 years.** Limited data from clinical trials for cIAI or cUTI in children ≥9 months (weight-based dosing: aztreonam 50 mg/kg / avibactam 25 mg/kg IV over 3 hours every 6–8 hours; max single dose = 3 g aztreonam/1.5 g avibactam). Dosing depends on local protocols and renal function.
- Verify with infectious disease specialist and current pediatric guidelines.
## Dose Adjustments
- **Renal impairment:** Adjust as above; use Cockcroft-Gault for CrCl
- **Hepatic impairment:** No adjustment required
## Contraindications
- Hypersensitivity to aztreonam, avibactam, or any component of the formulation
- Severe allergic reactions to other β-lactams (potential cross-reactivity is very low but caution advised)
## Adverse Effects
- Nausea, vomiting, diarrhea (including *Clostridioides difficile*)
- Injection site reactions (phlebitis, pain)
- Elevated liver enzymes, transaminitis
- Headache, dizziness
- Rash, pruritus
- Serious: anaphylaxis, hypersensitivity, seizures (rare, more likely in renal impairment)
## Key Drug Interactions
- **Probenecid:** Decreases renal clearance of aztreonam and avibactam; co-administration not recommended
- **Antibiotics:** No major antagonistic interactions; synergistic when used with other β-lactams/β-lactamase inhibitors (e.g., ceftazidime-avibactam) for MBLs
- **Live bacterial vaccines (e.g., BCG):** Avoid during use due to potential reduction in efficacy
## Monitoring
- Renal function (baseline and at least every 48–72 hours; adjust dosing accordingly)
- Liver function tests (baseline and weekly if prolonged use)
- Signs of infusion reactions or hypersensitivity during administration (especially with prolonged infusion)
- Clinical response and cultures (blood, urine, respiratory) to guide duration
## Clinical Pearls
- AVYCAZ is a fixed-dose combination with avibactam; it does NOT contain added clavulanate, tazobactam, or sulbactam
- For MBL-producing organisms (e.g., NDM, VIM), dual therapy with ceftazidime-avibactam plus aztreonam (or AVYCAZ alone) is used to provide avibactam to protect aztreonam; this is off-label but increasingly standard in carbapenem-resistant infections
- Infuse over 3 hours (prolonged infusion) for optimal pharmacokinetic/pharmacodynamic target attainment
- No reliable oral alternative exists for this combination; IV only
- In renal impairment, dosing adjustments are critical to avoid neurotoxicity and excessive accumulation
*This information is for educational purposes only and does not replace clinical judgment. Always verify dosing, indications, and patient-specific details against current prescribing information (e.g., FDA/EMA labeling, local guidelines).*
