Usage
Ceftazidime is a third-generation cephalosporin antibiotic prescribed for a wide range of bacterial infections. These include, but are not limited to, meningitis, pneumonia, sepsis, urinary tract infections, joint infections, malignant otitis externa, Pseudomonas aeruginosa infections, and vibrio infections. Its pharmacological classification is antibiotic. Ceftazidime exerts its bactericidal effect by inhibiting bacterial cell wall synthesis.
Alternate Names
Ceftazidime is also known internationally by various names. Common brand names include Fortaz, Tazicef, Ceptaz, and Ceftazidime Kabi.
How It Works
Pharmacodynamics: Ceftazidime is a beta-lactam antibiotic that disrupts the synthesis of the peptidoglycan layer, a crucial component of bacterial cell walls. This disruption leads to cell lysis and bacterial death. Ceftazidime has a broad spectrum of activity against gram-negative bacteria, including Pseudomonas aeruginosa, and some gram-positive bacteria. It achieves high concentrations in various tissues and fluids, including cerebrospinal fluid, making it effective against meningitis.
Pharmacokinetics: Ceftazidime is administered parenterally (IV or IM). It is poorly absorbed orally. After administration, it is widely distributed throughout the body, achieving therapeutic concentrations in various tissues and fluids. It is primarily eliminated by renal excretion, with a small amount metabolized to inactive metabolites. The half-life is approximately 2 hours in patients with normal renal function.
Mode of action: Ceftazidime binds to penicillin-binding proteins (PBPs), which are enzymes essential for bacterial cell wall synthesis. This binding inhibits the transpeptidation and cross-linking reactions necessary for peptidoglycan formation, leading to a weakened cell wall and bacterial death.
Elimination: Ceftazidime is excreted primarily through the kidneys via glomerular filtration.
Dosage
Standard Dosage
Adults:
The usual adult dose is 1 to 2 grams every 8 to 12 hours via IV or IM injection, or IV infusion. The maximum daily dose can reach up to 9 grams, but typically does not exceed 6 grams. The dosage and route of administration are determined by the infection’s severity, the causative organism’s susceptibility, and the patient’s renal function.
Children:
- Neonates (0-2 months): 25-60 mg/kg/day, divided into two doses.
- Infants and children (over 2 months): 30-100 mg/kg/day (up to 150 mg/kg/day for severe infections), divided into 2-3 doses. Maximum daily dose: 6 grams.
- Children over 12 months: 25-100 mg/kg/day, given in two or three divided doses. For severe infections (e.g., immunocompromised, cystic fibrosis), the maximum dose is 6g/day.
Special Cases:
- Elderly Patients: For patients over 80 years old, the maximum daily dose should not typically exceed 3 grams due to age-related decrease in renal clearance.
- Patients with Renal Impairment: Dosage adjustments are necessary. See “Dosage Adjustments” section below.
- Patients with Hepatic Dysfunction: No dosage adjustments are typically required for mild to moderate hepatic dysfunction. Data for severe hepatic dysfunction is limited; close monitoring is advised.
- Patients with Comorbid Conditions: Consider underlying diseases like diabetes or cardiovascular issues when adjusting treatment duration.
Clinical Use Cases
Dosing recommendations are similar across various clinical settings, considering the standard dosage and adjustments for specific patient populations. For conditions like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations, the dose should be based on the infection being treated and follow the guidelines described above.
Dosage Adjustments
Ceftazidime dosage must be adjusted in patients with renal impairment based on creatinine clearance (CrCl):
- CrCl 31-50 mL/min: 1-2 g every 12 hours
- CrCl 16-30 mL/min: 1-2 g every 24 hours
- CrCl 6-15 mL/min: 500 mg - 1 g every 24 hours
- CrCl < 5 mL/min: 500 mg - 1 g every 48 hours
For patients on hemodialysis, a 1 gram loading dose is recommended, followed by 1 gram after each dialysis session. For patients on continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD), consult specific guidelines for dose optimization.
Side Effects
Common Side Effects
- Pain, swelling, redness, or bleeding at the injection site
- Diarrhea
- Nausea
- Vomiting
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis, angioedema)
- Clostridium difficile-associated diarrhea (pseudomembranous colitis)
- Seizures (particularly at high doses or in patients with renal impairment)
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Kidney damage
- Liver damage
- Neutropenia
- Thrombocytopenia
Long-Term Effects
Prolonged use can result in the development of antibiotic resistance and superinfections, such as fungal infections.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, pseudomembranous colitis, seizures, severe skin reactions, nephrotoxicity, and hepatotoxicity.
Contraindications
Ceftazidime is contraindicated in patients with a known hypersensitivity to ceftazidime, other cephalosporins, or any other β-lactam antibacterial agent (penicillins, monobactams, carbapenems). Caution is advised in patients with a history of penicillin allergy.
Drug Interactions
Ceftazidime may interact with aminoglycosides, potentially increasing the risk of nephrotoxicity. Probenecid can decrease ceftazidime elimination, leading to higher serum levels. Ceftazidime may also interact with certain oral contraceptives, anticoagulants like warfarin, and other medications metabolized by CYP450 enzymes. Alcohol can slow the immune response, potentially interfering with the efficacy of the antibiotic. Always consult a comprehensive drug interaction resource before co-prescribing medications with ceftazidime.
Pregnancy and Breastfeeding
Ceftazidime is generally considered safe to use during pregnancy, as it is not expected to increase the risk of major congenital malformations. It is also considered safe during breastfeeding, although monitoring the infant for gastrointestinal symptoms (e.g., diarrhea, thrush) is recommended. However, the decision to use ceftazidime in pregnant or breastfeeding women should be made based on a careful risk-benefit assessment.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial cell wall synthesis by binding to PBPs.
- Side Effects: Common: Injection site reactions, diarrhea. Serious: Allergic reactions, C. difficile infection, seizures, severe skin reactions.
- Contraindications: Hypersensitivity to cephalosporins or other β-lactam antibiotics.
- Drug Interactions: Aminoglycosides, probenecid, oral contraceptives, anticoagulants.
- Pregnancy & Breastfeeding: Generally considered safe; monitor infant for GI symptoms.
- Dosage: Adults: 1-2g every 8-12 hours IV/IM. Children: Dose by weight. Renal adjustments needed.
- Monitoring Parameters: Renal function, signs of superinfection, liver enzymes, complete blood count.
Popular Combinations
Ceftazidime is sometimes combined with other antibiotics, such as aminoglycosides (e.g., gentamicin), to broaden the spectrum of coverage or to enhance efficacy against certain resistant organisms. However, this combination increases the risk of nephrotoxicity, and careful monitoring is essential. Avibactam is a beta-lactamase inhibitor combined with ceftazidime to address certain drug-resistant bacteria.
Precautions
General precautions include checking for allergies, monitoring renal function, assessing for signs of superinfection, and adjusting dosage as needed for specific patient populations (elderly, renally impaired, etc.). Lifestyle considerations like alcohol consumption should be discussed with the patient.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ceftazidime?
A: Adults: 1-2 g IV/IM every 8-12 hours. Children: 25-150 mg/kg/day divided into 2-3 doses (adjust based on age and infection severity). Renal adjustments are crucial.
Q2: How is Ceftazidime administered?
A: Intravenously (IV) or intramuscularly (IM) injection or IV infusion.
Q3: What are the common side effects of Ceftazidime?
A: Pain, redness, or swelling at the injection site, diarrhea, nausea, vomiting.
Q4: What are the serious side effects of Ceftazidime?
A: Allergic reactions (including anaphylaxis), C. difficile infection, seizures, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
Q5: What are the contraindications for Ceftazidime?
A: Hypersensitivity to ceftazidime, other cephalosporins, or other β-lactam antibiotics.
Q6: Does Ceftazidime interact with other medications?
A: Yes, it can interact with aminoglycosides (increased nephrotoxicity risk), probenecid, oral contraceptives, and anticoagulants. Check drug interaction resources for a complete list.
Q7: Can Ceftazidime be used during pregnancy and breastfeeding?
A: Generally considered safe for both, but clinical judgment is essential. Monitor infants for GI symptoms during breastfeeding.
Q8: What should be monitored in patients receiving Ceftazidime?
A: Renal function, signs of superinfection, liver function tests, and complete blood count.
Q9: What is the mechanism of action of Ceftazidime?
A: It inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins.
Q10: Is Ceftazidime effective against Pseudomonas aeruginosa?
A: Yes, it is active against many strains of P. aeruginosa, making it a valuable option for infections caused by this organism.
Q11: What is the difference between Ceftazidime and other cephalosporins?
A: Ceftazidime is a third-generation cephalosporin with greater activity against gram-negative bacteria, including P. aeruginosa, compared to earlier generations.
