ceftazidime-avibactam
Brand: Avycaz
Prototype: ceftazidime
Drug Class: beta-lactam/beta-lactamase inhibitor combination
Drug Family: antibiotic
Subclass: novel beta-lactam/beta-lactamase inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Ceftazidime inhibits PBPs; avibactam is a non-beta-lactam beta-lactamase inhibitor that reversibly inhibits KPC, OXA-48, and AmpC carbapenemases, restoring ceftazidime's activity against carbapenem-resistant Enterobacteriaceae.
penicillin-binding proteins (PBPs)KPC/OXA-48/AmpC beta-lactamases
Indications
- complicated UTI (cUTI)
- complicated intra-abdominal infection (cIAI)
- hospital-acquired pneumonia/VAP due to carbapenem-resistant organisms
- KPC-producing Enterobacteriaceae infections
Contraindications
- cephalosporin hypersensitivity
Adverse Effects
Common
- diarrhea
- nausea
- vomiting
- headache
Serious
- C. difficile colitis
- anaphylaxis
- neurological adverse effects (seizures, encephalopathy)
- renal impairment
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | both components widely distributed; CSF penetration similar to ceftazidime |
| Metabolism | ceftazidime: not metabolized; avibactam: minimal |
| Excretion | renal (both components, unchanged); dose-critical adjustment in CKD |
| Half-life | ceftazidime 2.7 h; avibactam 2.7 h |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 8 hours |
| Protein Binding | ceftazidime 10%; avibactam 8% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| probenecid | reduces renal excretion of avibactam | minor |
| nephrotoxic agents | additive renal toxicity risk | moderate |
Nursing Considerations
- Administer IV over 120 minutes (2-hour infusion) per prescribing information; administer each dose precisely on schedule for severe infections.
- Renal dose adjustment is mandatory; use adjusted body weight for patients with obesity; consult pharmacist for dosing in CRRT.
- Monitor for neurological adverse events including seizures, particularly in patients with renal impairment where accumulation of ceftazidime can occur.
- Obtain cultures before starting therapy; monitor for development of resistance during treatment.
Clinical Pearls
- Ceftazidime-avibactam is a key agent in the armamentarium against carbapenem-resistant Enterobacteriaceae (CRE) producing KPC enzymes.
- Avibactam does NOT inhibit metallo-beta-lactamases (NDM, VIM, IMP); ceftazidime-avibactam will not be effective against NDM-producing organisms without combination therapy.
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
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