Usage
Avibactam + Ceftazidime is prescribed for the treatment of various bacterial infections caused by susceptible Gram-negative bacteria. It is particularly useful against complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) including pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). It’s also employed for infections due to aerobic Gram-negative organisms in patients with limited treatment options where other antibiotics have failed or are unsuitable. Its pharmacological classification is “antibiotic,” specifically a combination of a beta-lactam antibiotic (ceftazidime) and a beta-lactamase inhibitor (avibactam). Ceftazidime exerts its antibacterial action by binding to and inhibiting penicillin-binding proteins (PBPs), crucial enzymes involved in bacterial cell wall synthesis. Avibactam protects ceftazidime from degradation by certain beta-lactamases produced by bacteria, thereby expanding ceftazidime’s effectiveness against resistant strains.
Alternate Names
A common alternate name is Ceftazidime/Avibactam. Popular brand names include Avycaz and Zavicefta.
How It Works
Pharmacodynamics: Ceftazidime inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), leading to bacterial cell death. Avibactam inhibits a broad range of beta-lactamases, including Ambler classes A, C, and some D enzymes. It restores ceftazidime’s activity against bacteria that would otherwise be resistant.
Pharmacokinetics:
- Absorption: Administered intravenously, achieving rapid and complete systemic availability.
- Metabolism: Ceftazidime undergoes minimal metabolism. Avibactam is also minimally metabolized.
- Elimination: Both drugs are primarily eliminated via renal excretion, necessitating dose adjustments in patients with renal impairment.
Mode of Action: Ceftazidime primarily targets PBP3 in Gram-negative bacteria. Avibactam forms a covalent adduct with the active site serine residue of beta-lactamases, preventing their hydrolytic activity against ceftazidime.
Dosage
Standard Dosage
Adults:
2.5 g (ceftazidime 2 g + avibactam 0.5 g) IV every 8 hours, infused over 120 minutes for Avycaz or 2 hours for Zavicefta.
Children (3 months to <18 years):
Dosing depends on age, weight, and renal function.
Special Cases:
- Elderly Patients: No dose adjustment required unless renal impairment is present.
- Patients with Renal Impairment: Dose adjustments are required based on CrCl.
- Patients with Hepatic Dysfunction: No dose adjustment required.
- Patients with Comorbid Conditions: Careful monitoring is advisable, especially in patients with seizures or neurological conditions.
Clinical Use Cases
Dosage recommendations remain consistent across various clinical settings, including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations. Adjust dose based on renal function.
Dosage Adjustments
Dosage modifications based on renal impairment are needed. Refer to specific brand labeling for detailed dose reduction guidelines based on CrCl or eGFR.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Headache
- Rash
- Elevated liver enzymes
- Injection site reactions
Rare but Serious Side Effects
- Clostridium difficile-associated diarrhea
- Seizures (especially in patients with renal impairment)
- Allergic reactions (including anaphylaxis)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
Long-Term Effects
Long-term effects are rarely reported.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, Clostridium difficile infection, and seizures.
Contraindications
- Hypersensitivity to ceftazidime, avibactam, or other cephalosporins.
Drug Interactions
- Probenecid may decrease renal clearance of ceftazidime.
Pregnancy and Breastfeeding
Ceftazidime/avibactam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data are available regarding the use of this medication during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Ceftazidime: PBP inhibition; Avibactam: beta-lactamase inhibition.
- Side Effects: Diarrhea, nausea, vomiting, rash, C. difficile infection, seizures.
- Contraindications: Hypersensitivity to ceftazidime, avibactam, or other cephalosporins.
- Drug Interactions: Probenecid.
- Pregnancy & Breastfeeding: Caution advised; potential benefits must outweigh risks.
- Dosage: Adults: 2.5 g IV q8h; Children: dose based on age, weight, and renal function.
- Monitoring Parameters: Renal function (CrCl or eGFR), signs of hypersensitivity, signs of superinfection (e.g., C. difficile infection), neurological status.
Popular Combinations
Metronidazole is frequently combined with Avibactam/Ceftazidime for cIAI. Other antibacterials active against Gram-positive pathogens may be added when such infections are suspected or confirmed.
Precautions
Monitor renal function, particularly in patients with pre-existing renal impairment. Assess for history of allergies to beta-lactams. Observe for signs and symptoms of C. difficile infection. In patients with a history of seizures, monitor for neurological adverse events.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Avibactam + Ceftazidime?
A: Adults: 2.5 g IV every 8 hours. Children: Dosage depends on age, weight and renal function. Dose adjustments needed for patients with renal impairment.
Q2: What are the most common side effects?
A: Diarrhea, nausea, vomiting, headache, and rash.
Q3: Is Avibactam + Ceftazidime safe to use in pregnancy?
A: Limited data are available. Use only if the potential benefit outweighs the potential risk to the fetus.
Q4: How is Avibactam + Ceftazidime administered?
A: Intravenous infusion over 120 minutes (Avycaz) or 2 hours (Zavicefta).
Q5: What infections is Avibactam + Ceftazidime commonly used to treat?
A: cIAI, cUTI (including pyelonephritis), HAP, and VAP.
Q6: Are there any significant drug interactions?
A: Probenecid may reduce the renal clearance of ceftazidime.
Q7: What is the mechanism of action of Avibactam + Ceftazidime?
A: Ceftazidime: Inhibits bacterial cell wall synthesis; Avibactam: Protects ceftazidime from beta-lactamase degradation.
Q8: Does hepatic impairment affect the dosing of Avibactam + Ceftazidime?
A: No dosage adjustment is required for hepatic impairment.
Q9: What should be monitored in patients receiving Avibactam + Ceftazidime?
A: Renal function, signs of allergic reactions, and potential superinfections, such as C. difficile infection.
Q10: What is the difference between Avycaz and Zavicefta?
A: Both are brand names for ceftazidime/avibactam, the primary difference being the recommended infusion times.
