Avibactam is not available as a standalone drug but is used in combination with other antibiotics, such as ceftazidime. This information pertains to the combination of ceftazidime/avibactam.
Usage
Ceftazidime/avibactam is prescribed for the treatment of complicated intra-abdominal infections (cIAI) (in combination with metronidazole), complicated urinary tract infections (cUTI) including pyelonephritis, and hospital-acquired pneumonia/ventilator-associated bacterial pneumonia (HAP/VABP) in adults and certain pediatric populations. It is classified as a beta-lactam/beta-lactamase inhibitor combination. Avibactam itself acts as a beta-lactamase inhibitor, protecting ceftazidime from degradation by bacterial enzymes, thereby extending its effectiveness against resistant strains.
Alternate Names
Ceftazidime/avibactam is marketed under brand names such as Avycaz® and Zavicefta®. There are no widely used alternate names for avibactam itself.
How It Works
Pharmacodynamics: Ceftazidime exerts its antibacterial action by binding to penicillin-binding proteins (PBPs), disrupting bacterial cell wall synthesis, leading to cell death. Avibactam inhibits a wide range of beta-lactamases (enzymes produced by bacteria that degrade beta-lactam antibiotics), preventing ceftazidime’s breakdown and expanding its spectrum of activity against resistant organisms.
Pharmacokinetics: Both ceftazidime and avibactam are administered intravenously. They distribute widely into various body tissues and fluids, including the lungs. Ceftazidime is primarily eliminated renally as unchanged drug, while avibactam is eliminated through both renal and non-renal pathways (including metabolism).
Mode of Action: Avibactam acts as a suicide inhibitor of beta-lactamases. It forms a covalent adduct with the active site of these enzymes, irreversibly inactivating them and preventing their degradation of ceftazidime.
Elimination: Ceftazidime is primarily eliminated by renal excretion. Avibactam is eliminated by multiple pathways, including renal excretion (as unchanged drug and metabolites) and non-renal mechanisms involving hydrolysis and conjugation.
Dosage
Standard Dosage
Adults:
- Normal Renal Function (Creatinine Clearance [CrCl] > 50 mL/min): 2.5 grams (ceftazidime 2 g/avibactam 0.5 g) every 8 hours by intravenous (IV) infusion over 2 hours.
- cIAI: Administer with metronidazole.
Children:
- 3 months to <18 years (CrCl >50 mL/min) cIAI/cUTI including Pyelonephritis: 62.5 mg/kg (ceftazidime 50 mg/kg, avibactam 12.5 mg/kg) IV every 8 hours (max 2g/0.5g) infused over 2 hours. Patients <18 years of age with renal impairment have separate guidelines.
Special Cases:
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Elderly Patients: No dose adjustment is necessary for patients over 65 years with normal renal function (CrCl > 50 mL/min). Dosage should be adjusted for renal impairment based on CrCl.
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Patients with Renal Impairment: Dosage adjustments are needed based on the patient’s CrCl.
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Patients with Hepatic Dysfunction: No dose adjustment is required.
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Patients with Comorbid Conditions: Close monitoring is recommended.
Clinical Use Cases
Dosing is consistent across approved clinical use cases. Refer to the Standard Dosage section.
Dosage Adjustments
Dosage adjustments are based on creatinine clearance (CrCl). Consult the package insert or reputable clinical resources for specific dose adjustments.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, constipation, headache, and infusion site reactions.
Rare but Serious Side Effects:
Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures, acute kidney injury, and hepatotoxicity.
Long-Term Effects:
Potential for development of antibiotic resistance with prolonged use.
Adverse Drug Reactions (ADR):
Severe hypersensitivity reactions and C. difficile infection require immediate intervention.
Contraindications
Hypersensitivity to ceftazidime, avibactam, or other cephalosporins. Severe hypersensitivity to any other beta-lactam antibacterial agent (penicillins, carbapenems, monobactams).
Drug Interactions
Probenecid can decrease avibactam elimination and is not recommended for co-administration. Ceftazidime may cause false-positive urine glucose tests with some methods. Use enzymatic glucose oxidase methods.
Pregnancy and Breastfeeding
Ceftazidime is excreted in human milk in low concentrations. The presence of avibactam in human milk is unknown. Use with caution in breastfeeding mothers. If the drug is necessary, monitor the infant for adverse effects.
Drug Profile Summary
- Mechanism of Action: Ceftazidime inhibits bacterial cell wall synthesis; avibactam protects ceftazidime from beta-lactamase degradation.
- Side Effects: Nausea, vomiting, diarrhea, hypersensitivity reactions, C. difficile infection, seizures.
- Contraindications: Hypersensitivity to ceftazidime, avibactam, cephalosporins, or other beta-lactams.
- Drug Interactions: Probenecid.
- Pregnancy & Breastfeeding: Use with caution if clearly needed; ceftazidime is present in breast milk, avibactam’s presence is unknown.
- Dosage: Varies according to renal function. See Dosage section.
- Monitoring Parameters: Renal function (serum creatinine, CrCl), signs of hypersensitivity, and clinical response to therapy.
Popular Combinations
Ceftazidime/avibactam is often used in combination with metronidazole for the treatment of cIAI.
Precautions
Assess renal function, history of drug allergies (especially to beta-lactams), and monitor for signs of superinfection (e.g., C. difficile infection). Caution is advised when using in patients with a history of seizures.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ceftazidime/Avibactam?
A: See the detailed Dosage section above. It varies based on age, renal function, and the infection being treated.
Q2: How is Ceftazidime/Avibactam administered?
A: It is administered intravenously over a period of 2 hours.
Q3: What is the role of avibactam in this combination?
A: Avibactam protects ceftazidime from being broken down by bacterial beta-lactamases, expanding its activity against resistant bacteria.
Q4: What are the most common side effects?
A: Common side effects include nausea, vomiting, diarrhea, and constipation.
Q5: Are there any serious side effects to be aware of?
A: Yes, rare but serious side effects include hypersensitivity reactions (including anaphylaxis), Clostridioides difficile infection, and seizures.
Q6: Can Ceftazidime/Avibactam be used in pregnant or breastfeeding women?
A: It should be used with caution during pregnancy and breastfeeding only if the potential benefit outweighs the risk. Ceftazidime is known to be excreted in breast milk; avibactam’s presence is unknown.
Q7: What are the contraindications to using this medication?
A: Contraindications include known serious hypersensitivity to ceftazidime, avibactam, or other cephalosporins.
Q8: Are there any important drug interactions?
A: Concurrent use of probenecid is not recommended as it can decrease the elimination of avibactam.
Q9: How should dosage be adjusted for patients with renal impairment?
A: Dosage adjustments are essential for patients with renal impairment. Consult the prescribing information for specific recommendations based on creatinine clearance (CrCl).
