Tazobactum (Piperacillin/Tazobactam)

Usage

Tazobactam is a combination medication consisting of the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. It is prescribed for a variety of bacterial infections, including:

• Intra-abdominal infections: Such as appendicitis with rupture or abscess, and peritonitis.
• Skin and skin structure infections: Including uncomplicated and complicated cellulitis.
• Gynecological infections: Such as endometritis and pelvic inflammatory disease.
• Respiratory tract infections: Including community-acquired and nosocomial pneumonia.
• Bone and joint infections.
• Septicemia.
• Urinary tract infections.
• Bacterial infections in neutropenic patients.

Pharmacological Classification: Antibiotic (β-lactam/β-lactamase inhibitor combination).

Mechanism of Action: Piperacillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Tazobactam, a β-lactamase inhibitor, protects piperacillin from degradation by many bacterial β-lactamases, extending its spectrum of activity.

Alternate Names

• Piperacillin/Tazobactam
• Pip/Tazo

Brand Names: Tazocin, Zosyn, PipTaz-AFT.

How It Works

Pharmacodynamics: Piperacillin/tazobactam exhibits bactericidal activity against a wide range of gram-positive and gram-negative bacteria, including many strains producing β-lactamases. Tazobactam effectively inhibits most plasmid-mediated penicillinases and some chromosomal β-lactamases, significantly broadening piperacillin’s spectrum.

Pharmacokinetics:

• Absorption: Administered intravenously, resulting in rapid and complete absorption.
• Distribution: Widely distributed throughout the body, including tissues and fluids. Crosses the placenta and is found in low concentrations in breast milk.
• Metabolism: Piperacillin is minimally metabolized. Tazobactam is metabolized to a minor extent.
• Elimination: Both drugs are primarily excreted renally, with some elimination in bile. Dose adjustments are needed for patients with renal impairment.

Mode of Action: Piperacillin targets bacterial PBPs, crucial enzymes involved in the final stages of peptidoglycan synthesis for the bacterial cell wall. By binding to PBPs, piperacillin inhibits the cross-linking of peptidoglycan strands, leading to cell wall instability and bacterial lysis.

Receptor Binding/Enzyme Inhibition: Piperacillin binds to and inhibits PBPs. Tazobactam inhibits bacterial β-lactamases by forming a stable complex with the enzyme’s active site, preventing the hydrolysis of piperacillin.

Dosage

Standard Dosage

Adults:

• Most Indications: 3.375 g intravenously every 6 hours (over 30 minutes), or 4.5 g every 8 hours.
• Nosocomial Pneumonia: 4.5 g every 6 hours, plus an aminoglycoside.
• Severe Infections: Up to 18 g piperacillin/2.25 g tazobactam per day in divided doses.

Children (2 months to 12 years):

• 2 months to 9 months: 80 mg piperacillin/10 mg tazobactam per kg body weight every 6-8 hours (IV infusion over 30 minutes).
• >9 months and ≤ 40 kg: 100 mg piperacillin/12.5 mg tazobactam per kg body weight every 6-8 hours (IV infusion over 30 minutes).
• >40 kg: Same as adult dose.
• Duration of treatment: Typically 7-14 days, depending on infection severity and response.

Special Cases:

• Elderly Patients: Dose adjustment may be needed for those with impaired renal function.
• Patients with Renal Impairment: Dosage should be reduced based on creatinine clearance.
• Patients with Hepatic Dysfunction: No specific dose adjustment is usually necessary.
• Patients with Comorbid Conditions: Caution is advised for those with cystic fibrosis, seizures, or electrolyte imbalances.

Clinical Use Cases:

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use: Dosing is similar to standard recommendations, but may be adjusted based on infection severity and patient-specific factors.
• Emergency Situations: Dosage may be increased in life-threatening situations.

Dosage Adjustments:

Dosage modification is essential for renal impairment. Consult specific guidelines for creatinine clearance-based recommendations.

Side Effects

Common Side Effects:

• Diarrhea
• Constipation
• Nausea
• Headache
• Insomnia
• Rash
• Pruritus

Rare but Serious Side Effects:

• Clostridioides difficile infection
• Allergic reactions (including anaphylaxis)
• Thrombocytopenia (low platelet count)
• Neutropenia (low white blood cell count)
• Seizures
• Acute kidney injury
• Liver dysfunction

Long-Term Effects: No significant long-term adverse effects are typically associated with the usual course of Tazobactam therapy. However, prolonged use of any antibiotic may contribute to antibiotic resistance.

Contraindications

• Hypersensitivity to piperacillin, tazobactam, penicillins, cephalosporins, or β-lactamase inhibitors.

Drug Interactions

• Methotrexate: Tazobactam can decrease methotrexate clearance, leading to increased serum levels and toxicity.
• Warfarin: Tazobactam may enhance the anticoagulant effect of warfarin. Monitor INR closely.
• Probenecid: Concomitant use with probenecid can increase piperacillin levels.
• Aminoglycosides: Synergistic effects are seen against some gram-negative bacteria, but do not administer in the same IV line due to incompatibility.
• Vecuronium: Tazobactam may prolong the neuromuscular blockade of vecuronium and other neuromuscular blocking agents.
• Other medications: Numerous other drug interactions are possible; consult a comprehensive drug interaction resource.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (Australian categorization). Use during pregnancy only if clearly needed and the benefit outweighs the risk. Piperacillin and tazobactam cross the placenta.
• Breastfeeding: Piperacillin is present in low concentrations in breast milk. Tazobactam concentrations in human milk are unknown. Exercise caution when administering to breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Piperacillin inhibits bacterial cell wall synthesis; tazobactam protects piperacillin from β-lactamase degradation.
• Side Effects: Diarrhea, constipation, nausea, headache, insomnia, rash, allergic reactions, C. difficile infection, thrombocytopenia, neutropenia.
• Contraindications: Hypersensitivity to penicillins, cephalosporins, or β-lactamase inhibitors.
• Drug Interactions: Methotrexate, warfarin, probenecid, aminoglycosides, vecuronium.
• Pregnancy & Breastfeeding: Use cautiously if benefits outweigh risks.
• Dosage: Adults: 3.375 g IV every 6 hours or 4.5 g IV every 8 hours. Children: weight-based dosing.
• Monitoring Parameters: Renal function, signs of infection, complete blood count, liver function tests, observation for allergic reactions.

Popular Combinations

• Tazobactam is often combined with an aminoglycoside (e.g., gentamicin, tobramycin) for the treatment of severe infections, particularly those caused by Pseudomonas aeruginosa.

Precautions

• Monitor for signs of allergic reactions.
• Assess renal function before and during treatment.
• Observe for C. difficile infection.
• Monitor for bleeding or signs of thrombocytopenia.
• Monitor electrolyte levels, especially potassium, in patients receiving concomitant diuretics or cytotoxic agents.
• Dosage adjustment is crucial for patients with renal impairment.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Tazobactam?

A: Adults: 3.375 g IV every 6 hours or 4.5 g IV every 8 hours. Children: weight-based dosing. Adjust dose for renal impairment.

Q2: What are the common side effects of Tazobactam?

A: Diarrhea, constipation, nausea, headache, and insomnia are common side effects.

Q3: What are the serious side effects of Tazobactam?

A: Clostridioides difficile infection, allergic reactions, bleeding, thrombocytopenia, neutropenia, and seizures are rare but serious side effects.

Q4: What are the contraindications for Tazobactam?

A: A history of allergic reactions to penicillins, cephalosporins, or β-lactamase inhibitors.

Q5: How is Tazobactam administered?

A: Intravenous infusion over 30 minutes.

Q6: Does Tazobactam interact with other medications?

A: Yes, it can interact with methotrexate, warfarin, probenecid, aminoglycosides, and vecuronium, among others. Consult a comprehensive resource for a complete list of interactions.

Q7: Can Tazobactam be used during pregnancy or breastfeeding?

A: It should be used cautiously in pregnancy only if the benefit outweighs the potential risk. Exercise caution during breastfeeding, as piperacillin is excreted in breast milk and tazobactam’s presence is unknown.

Q8: What is the mechanism of action of Tazobactam?

A: Piperacillin inhibits bacterial cell wall synthesis, while tazobactam prevents its breakdown by bacterial enzymes (β-lactamases).

Q9: What infections can Tazobactam treat?

A: It is used to treat various bacterial infections, including intra-abdominal infections, pneumonia, skin infections, gynecological infections, urinary tract infections, and sepsis.

Q10: What monitoring parameters should be considered when using Tazobactam?

A: Renal function, signs and symptoms of infection, complete blood count, liver function tests, and observation for allergic reactions.

This information is current as of February 17, 2025, and is intended for use by qualified healthcare professionals. Always consult the latest prescribing information and specific product literature for detailed guidance. This information does not substitute professional medical advice.