Piperacillin + Tazobactam

Usage

Piperacillin + Tazobactam is prescribed for a variety of bacterial infections, including:

• Intra-abdominal infections (e.g., appendicitis, peritonitis, biliary infections)
• Skin and soft tissue infections (including diabetic foot infections)
• Respiratory tract infections (e.g., nosocomial pneumonia)
• Urinary tract infections (including pyelonephritis)
• Sepsis
• Febrile neutropenia
• Gynecological infections (e.g., pelvic inflammatory disease)
• Bone and joint infections
• Polymicrobial infections

Pharmacological Classification: Antibiotic; specifically, a beta-lactam antibiotic combined with a beta-lactamase inhibitor.

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

Alternate Names

Piperacillin/Tazobactam

Brand Names: Tazocin®, Zosyn®, PipTaz®

How It Works

Pharmacodynamics: Piperacillin + Tazobactam exerts its bactericidal effect by disrupting bacterial cell wall synthesis, ultimately leading to cell lysis and death. Tazobactam enhances piperacillin’s effectiveness by inhibiting a wide range of beta-lactamases produced by bacteria, which would otherwise inactivate piperacillin.

Pharmacokinetics:

• Absorption: Administered intravenously, achieving rapid and complete bioavailability.
• Distribution: Distributes widely into various tissues and body fluids, including the pleural, peritoneal, and cerebrospinal fluids.
• Metabolism: Piperacillin undergoes minimal metabolism. Tazobactam is partially metabolized to an inactive metabolite.
• Elimination: Primarily eliminated via renal excretion, with both piperacillin and tazobactam exhibiting a similar half-life.

Mode of Action: Piperacillin binds to PBPs, enzymes essential for bacterial cell wall synthesis. This binding disrupts the cross-linking of peptidoglycans, a crucial component of the cell wall, resulting in cell wall instability and eventual bacterial death. Tazobactam forms stable complexes with beta-lactamases, preventing them from hydrolyzing the beta-lactam ring of piperacillin.

Receptor Binding/Enzyme Inhibition: Piperacillin acts by inhibiting PBPs. Tazobactam inhibits beta-lactamases.

Elimination Pathways: Primarily renal excretion.

Dosage

Standard Dosage

Adults:

• Standard dose: 3.375 g every 6 hours or 4.5 g every 8 hours, administered intravenously over 30 minutes.
• Maximum daily dose: Up to 18 g piperacillin/2.25 g tazobactam.

Children (2-12 years):

• Intra-abdominal infections: 100 mg piperacillin/12.5 mg tazobactam per kg every 8 hours IV.
• Febrile neutropenia: 80 mg piperacillin/10 mg tazobactam per kg every 6 hours IV (often combined with an aminoglycoside).
• Children >40 kg: Use adult dosing.
• Children < 2 years: Safety and efficacy not established.

Special Cases:

• Elderly Patients: Dose adjustment may be necessary in the presence of renal impairment.
• Patients with Renal Impairment: Dosage adjustment is necessary based on creatinine clearance (CrCl).
• Patients with Hepatic Dysfunction: No dose adjustment is typically needed.
• Patients with Comorbid Conditions: Consider individual patient factors.

Clinical Use Cases

Dosage and frequency should be tailored to the specific infection and patient condition. In severe infections, higher doses (up to 18 g piperacillin/2.25 g tazobactam per day) and more frequent administration (every 6 hours) may be necessary. Combination therapy with an aminoglycoside is often recommended for serious infections caused by Pseudomonas aeruginosa, especially in neutropenic patients. Dosage adjustments should be made in patients with renal impairment based on their creatinine clearance.

• Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Dosage should be adjusted according to the severity of the infection and patient factors.

Dosage Adjustments

See above under “Special Cases”.

Side Effects

Common Side Effects

• Diarrhea
• Constipation
• Nausea
• Vomiting
• Headache
• Rash
• Insomnia
• Pain at injection site
• Phlebitis

Rare but Serious Side Effects

• Allergic reactions (including anaphylaxis)
• Clostridium difficile infection (pseudomembranous colitis)
• Neutropenia
• Thrombocytopenia
• Seizures
• Acute kidney injury
• Hepatic dysfunction
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Long-Term Effects

With prolonged use: C. difficile infection, superinfections, antibiotic resistance.

Adverse Drug Reactions (ADR)

See “Rare but Serious Side Effects”

Contraindications

• Known hypersensitivity to piperacillin, tazobactam, any penicillin or cephalosporin, or any component of the formulation.

Drug Interactions

• Aminoglycosides: Synergistic against certain bacteria but physically incompatible and should not be mixed in the same IV solution. Administer separately.
• Probenecid: May increase piperacillin concentrations.
• Anticoagulants: May enhance anticoagulant effects.
• Methotrexate: Piperacillin may decrease methotrexate clearance.
• Vecuronium: Piperacillin may prolong neuromuscular blockade.
• Other medications: Consult a comprehensive drug interaction resource for specific interactions.

Pregnancy and Breastfeeding

• Pregnancy: Crosses the placenta. Use only if the potential benefit outweighs the potential risk to the fetus.
• Breastfeeding: Piperacillin is excreted in low concentrations in breast milk. Tazobactam concentrations in human milk are unknown. Caution is advised.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial cell wall synthesis. Tazobactam extends piperacillin’s spectrum by inhibiting beta-lactamases.
• Side Effects: Diarrhea, constipation, nausea, headache, rash, allergic reactions, C. difficile infection.
• Contraindications: Hypersensitivity to penicillins, cephalosporins, or beta-lactamase inhibitors.
• Drug Interactions: Aminoglycosides, probenecid, anticoagulants, methotrexate.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: Adults: 3.375 g every 6 hours or 4.5 g every 8 hours IV. Children: weight-based dosing.
• Monitoring Parameters: Renal function, liver function, complete blood count, signs of infection, clinical response.

Popular Combinations

Aminoglycosides (e.g., gentamicin, tobramycin, amikacin) for synergistic effect against Pseudomonas aeruginosa, especially in severe infections or neutropenic patients.

Precautions

• Hypersensitivity reactions
• Renal impairment
• Bleeding tendencies
• Clostridium difficile infection
• Monitor for superinfections.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Piperacillin + Tazobactam?

A: Adults: 3.375 g every 6 hours or 4.5 g every 8 hours IV. Children: weight-based dosing; see detailed dosage section.

Q2: What are the common side effects?

A: Diarrhea, constipation, nausea, rash, headache.

Q3: What are the serious side effects?

A: Allergic reactions (including anaphylaxis), C. difficile infection, neutropenia, thrombocytopenia.

Q4: How is Piperacillin + Tazobactam administered?

A: Intravenous infusion over 30 minutes.

Q5: Can it be used in pregnant or breastfeeding women?

A: Use with caution if potential benefit outweighs potential risk. Consult guidelines.

Q6: What are the contraindications?

A: Hypersensitivity to penicillins, cephalosporins, or beta-lactamase inhibitors.

Q7: Does Piperacillin + Tazobactam interact with other medications?

A: Yes, see the drug interactions section. Consult a drug interaction resource.

Q8: How should dosage be adjusted in renal impairment?

A: Dosage adjustment is necessary based on CrCl; see detailed dosage information.

Q9: What is the role of Tazobactam in this combination?

A: Tazobactam protects piperacillin from degradation by bacterial beta-lactamases, broadening its spectrum of activity.