Usage
Ceftazidime + Tazobactum is prescribed for a range of bacterial infections, including complicated intra-abdominal infections, complicated urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, ventilator-associated pneumonia, skin and soft tissue infections, gynecological infections, septicemia, and bacterial meningitis. It’s particularly useful against aerobic Gram-negative infections where treatment options are limited. It belongs to the pharmacological classification of Beta-lactam/beta-lactamase inhibitor combination antibiotics.
Ceftazidime, a cephalosporin antibiotic, disrupts bacterial cell wall synthesis. Tazobactam, a beta-lactamase inhibitor, protects ceftazidime from degradation by bacterial enzymes, broadening its effectiveness against resistant strains.
Alternate Names
Ceftazidime/Tazobactam is also known by several brand names globally including Avycaz and Zavicefta. Other brand names include Forzid TZ, Bioceft T, Ceftradon-TZ, Drucefta Plus, Fordime-TZ, Fotaram-TZ.
How It Works
Pharmacodynamics: Ceftazidime exerts its bactericidal effect by binding to penicillin-binding proteins (PBPs) in bacterial cell walls. This binding disrupts cell wall synthesis, ultimately leading to bacterial cell death. Tazobactam inhibits beta-lactamase enzymes produced by bacteria, preventing these enzymes from inactivating ceftazidime.
Pharmacokinetics: Administered intravenously or intramuscularly, Ceftazidime + Tazobactam is well-distributed in body tissues and fluids. It is primarily eliminated through renal excretion, with dosage adjustments necessary for patients with renal impairment. It is also excreted in breast milk. It is metabolised minimally.
Dosage
Standard Dosage
Adults:
The typical adult dose is 1 to 2 grams every 8 to 12 hours via IV or IM injection or infusion, adjusted according to the severity and type of infection. For complicated infections, doses up to 3 grams every 8 hours might be necessary.
Children:
Pediatric dosing varies depending on age and weight. For newborns up to 4 weeks old, 30 mg/kg every 12 hours is recommended. For infants and children older than 2 months, dosing ranges from 90-150 mg/kg/day for non-Pseudomonal infections, divided every 8 hours, and 90-300 mg/kg/day for severe infections.
Special Cases:
-
Elderly Patients: No dosage adjustment is generally required, although those over 80 may have a maximum daily dose of 3g. Renal function should be monitored closely.
-
Patients with Renal Impairment: Dosage adjustment is essential. Reduced doses and/or increased dosing intervals are required depending on the degree of impairment. Hemodialysis patients usually need a supplemental dose after dialysis.
-
Patients with Hepatic Dysfunction: While specific dose adjustments are not routinely needed, liver function monitoring is advisable.
-
Patients with Comorbid Conditions: Caution is advised for patients with a history of allergies, asthma, or other allergic conditions, bleeding disorders, seizures or neurological disorders, or gastrointestinal conditions (especially colitis). Monitor liver and renal function as well as for signs of superinfection (e.g., Clostridium difficile).
Clinical Use Cases
Dosage recommendations are based on the specific infection and its severity rather than clinical setting. However, typical dosing may be 1 to 2 grams every 8 to 12 hours administered intravenously or intramuscularly, adjusted according to patient-specific factors.
Dosage Adjustments
Dosage adjustments are based on creatinine clearance. Doses are generally reduced for creatinine clearance (CrCl) less than 50 mL/min.
Side Effects
Common Side Effects:
Nausea, diarrhea, headache, vomiting, dizziness, rash, injection site reactions (pain, swelling, redness), elevated liver enzymes.
Rare but Serious Side Effects:
Severe allergic reactions (including anaphylaxis), seizures, Clostridium difficile-associated diarrhea, hepatic dysfunction, neurotoxicity (encephalopathy), bleeding disorders (especially in patients with a history of bleeding disorders).
Long-Term Effects:
Potential long-term effects could include development of antibiotic resistance, vitamin K deficiency (which can affect blood clotting), or secondary infections (like Candida overgrowth, resulting in oral thrush or vaginal yeast infections).
Adverse Drug Reactions (ADR):
Clinically significant ADRs are rare, but if any severe allergic reactions, signs of acute renal failure, liver failure or central nervous system toxicity occur, immediate medical intervention is crucial.
Contraindications
Known hypersensitivity to ceftazidime, tazobactam, other cephalosporins, penicillins, or beta-lactamase inhibitors. A history of severe allergic reactions to any beta-lactam antibiotic is a contraindication.
Drug Interactions
- Clinically Significant Drug Interactions: Probenecid may increase Ceftazidime levels. Aminoglycosides and loop diuretics can potentiate nephrotoxicity. Some anticoagulants may require dosage adjustments. Avoid alcohol.
- CYP450 Interactions: No significant CYP450 interactions.
- Other Interactions: Interactions with oral microbiota. Toripalimab might decrease the effectiveness of immune checkpoint inhibitors. Tobramycin increases the chances of ototoxicity, Voclosporin increases the risk of nephrotoxicity.
Pregnancy and Breastfeeding
Ceftazidime + Tazobactam should be used during pregnancy and breastfeeding only if clearly needed. It is excreted in breast milk, and while generally considered safe, potential effects on the infant should be monitored.
Drug Profile Summary
- Mechanism of Action: Ceftazidime inhibits bacterial cell wall synthesis; tazobactam protects ceftazidime from beta-lactamase degradation.
- Side Effects: Nausea, diarrhea, headache, injection site reactions; rarely, severe allergic reactions, C. difficile infection, seizures.
- Contraindications: Hypersensitivity to cephalosporins, penicillins, or beta-lactamase inhibitors.
- Drug Interactions: Probenecid, aminoglycosides, loop diuretics, some anticoagulants.
- Pregnancy & Breastfeeding: Use with caution if clearly needed.
- Dosage: Adults: 1-2 g every 8-12 hours IV/IM; Children: Dose by weight and age.
- Monitoring Parameters: Renal function, liver function, signs of superinfection.
Popular Combinations
A common combination is Ceftazidime/Tazobactam with metronidazole for complicated intra-abdominal infections. Metronidazole adds anaerobic coverage, expanding the spectrum of activity.
Precautions
- General Precautions: Screen for allergies to beta-lactams. Monitor renal and hepatic function, particularly in at-risk individuals. Assess for signs of superinfection.
- Specific Populations: Pregnancy/breastfeeding: Use cautiously if benefits outweigh risks. Neonates/children: Adjust dosage by weight and age.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ceftazidime + Tazobactam?
A: Adult dosage is typically 1-2 grams every 8-12 hours IV/IM. Pediatric dosage is weight-based and depends on age and infection severity.
Q2: How is Ceftazidime + Tazobactam administered?
A: It is administered intravenously (IV) or intramuscularly (IM) as an injection or infusion.
Q3: What are the common side effects?
A: Common side effects include nausea, diarrhea, headache, and injection site reactions.
Q4: What are the serious side effects?
A: Serious side effects include severe allergic reactions, seizures, Clostridium difficile infection, and hepatic dysfunction.
Q5: What are the contraindications?
A: Contraindications include hypersensitivity to cephalosporins, penicillins, or beta-lactamase inhibitors.
Q6: What are the key drug interactions?
A: Key drug interactions involve probenecid, aminoglycosides, loop diuretics, and some anticoagulants.
Q7: Can it be used during pregnancy or breastfeeding?
A: Use cautiously if clearly needed during pregnancy or breastfeeding. Monitor for potential effects on the infant.
Q8: How should the dosage be adjusted for renal impairment?
A: Dosage adjustments are essential for renal impairment based on creatinine clearance.
Q9: How should Ceftazidime + Tazobactam be stored?
A: It should be stored as a sterile powder in single-dose vials. It should be stored at controlled room temperature (20°C to 25°C) and protected from light.
Q10: How does tazobactam enhance the activity of ceftazidime?
A: Tazobactam inhibits beta-lactamase, an enzyme produced by bacteria that can break down ceftazidime. By inhibiting beta-lactamase, tazobactam protects ceftazidime, making it more effective against resistant strains.
