How to administer piperacillin/tazobactam (Zosyn) intravenously?

Administration of Piperacillin/Tazobactam (Zosyn)

Piperacillin/tazobactam should be administered intravenously over 30 minutes after reconstitution and dilution, with standard adult dosing of 4.5g every 6 hours for serious infections, adjusting for renal function as needed. 1

Reconstitution and Dilution Process

For Adult Patients:

1. Reconstitution:

   • 4.5g vial: Add 20mL of compatible diluent
   • 3.375g vial: Add 15mL of compatible diluent
   • 2.25g vial: Add 10mL of compatible diluent
   • After reconstitution, concentration will be 202.5 mg/mL (180 mg/mL piperacillin and 22.5 mg/mL tazobactam)

2. Compatible Reconstitution Diluents:

   • 0.9% sodium chloride for injection
   • Sterile water for injection
   • Dextrose 5%
   • Bacteriostatic saline/parabens
   • Bacteriostatic water/parabens
   • Bacteriostatic saline/benzyl alcohol
   • Bacteriostatic water/benzyl alcohol

3. Dilution:

   • Further dilute reconstituted solution to 50-150mL in compatible IV solution
   • Compatible IV solutions: 0.9% sodium chloride, sterile water (max 50mL), dextran 6% in saline, dextrose 5%
   • Final concentration should be between 20-80 mg/mL of piperacillin component

4. Administration:

   • Administer by IV infusion over at least 30 minutes
   • Use infusion pump for accurate dosing
   • During infusion, discontinue primary infusion solution

Dosing Guidelines

Standard Dosing for Adults with Normal Renal Function:

• For most infections: 3.375g IV every 6 hours
• For nosocomial pneumonia: 4.5g IV every 6 hours
• For critically ill patients: 4.5g IV every 6 hours 2

Renal Adjustment:

• CrCl 20-40 mL/min: 2.25g every 6 hours (3.375g every 6 hours for nosocomial pneumonia)
• CrCl <20 mL/min: 2.25g every 8 hours (2.25g every 6 hours for nosocomial pneumonia)
• Hemodialysis: 2.25g every 12 hours (2.25g every 8 hours for nosocomial pneumonia) plus 0.75g after each dialysis session
• CAPD: 2.25g every 12 hours (2.25g every 8 hours for nosocomial pneumonia) 1

Pediatric Dosing:

• Children >40kg: Use adult dosing
• Children 9 months to 40kg: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours for appendicitis/peritonitis or every 6 hours for nosocomial pneumonia
• Children 2-9 months: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 hours for appendicitis/peritonitis or every 6 hours for nosocomial pneumonia 1

Extended or Continuous Infusion Considerations

For critically ill patients or infections with less susceptible organisms, consider extended or continuous infusion:

• Extended infusion: Administer over 3-4 hours instead of 30 minutes
• Continuous infusion: After initial loading dose, administer continuously over 24 hours

These methods may improve clinical outcomes by maintaining drug concentrations above MIC for longer periods 2

Important Precautions

1. Incompatibilities:

   • Do not use with Lactated Ringer's solution
   • Do not mix with other drugs in syringe or infusion bottle
   • Not chemically stable in solutions containing only sodium bicarbonate
   • Do not add to blood products or albumin hydrolysates 1

2. Aminoglycoside Compatibility:

   • Due to in vitro inactivation, administer piperacillin/tazobactam and aminoglycosides separately
   • If Y-site administration is necessary, specific compatibility conditions must be followed 1

3. Storage After Reconstitution:

   • Use immediately after reconstitution when possible
   • If storage needed: 24 hours at room temperature (20-25°C) or 48 hours refrigerated (2-8°C)
   • Do not freeze after reconstitution 1

Clinical Pearls

• For severe infections, consider loading doses to rapidly achieve therapeutic concentrations 2
• In critically ill patients, therapeutic drug monitoring may be beneficial due to pharmacokinetic variability 3
• Extended or continuous infusions may be particularly beneficial for patients with infections due to non-fermenting gram-negative bacilli 2
• Piperacillin/tazobactam is a preferred agent for critically ill patients with community-acquired intra-abdominal infections 2

By following these administration guidelines, you can optimize the therapeutic efficacy of piperacillin/tazobactam while minimizing potential complications.