General Information


  • Infused over 4 hours (extended-infusion protocol)
  • Continuous Infusion: 13.5 g over 24 hours in 250 to 500 mL D5W or NS
  • Loading doses can be administered over 30 minutes
  • If patient is also receiving Aminoglycoside therapy, separate doses due to potential for AG inactivation


  • 2.25g vial reconstituted with 10mL of D5W, NS or SWFI giving volume of 11.6mL (concentration piperacillin 172.4mg/mL)
  • 3.375g vial reconstituted with 15mL diluent giving volume of 17.36mL (concentration piperacillin 172.8mg/mL)
  • 4.5g vial reconstituted with 20mL diluent giving volume of 23.15mL (concentration piperacillin 172.8mg/mL)
  • Further dilute in D5W or NS to volume of 50-150 mL


  • NS, D5W, sterile water for injection (maximum volume 50 mL), dextran 6% in saline, or LR

Broad spectrum agent with anti-pseudomonal activity.

Used for severe infections including:

  • Pneumonia
  • Intra-abdominal/hepatobiliary
  • UTI
  • Polymicrobial skin and soft tissue infection
  • Febrile neutropenia

Tier 2 Protected Antimicrobial

  • Broad spectrum, but 1st line for common infections, comes with a high risk of poor stewardship if initial workup and follow-up are not in place

Strategies Used:

  1. Appropriate workup initially
  2. Pharmacists audit/de-escalate
  3. Set EBM Duration
  • SCr and BUN to monitor for nephrotoxicity
  • CBC with differential
  • PT and PTT, signs of bleeding
  • Serum electrolytes
  • LFTs
  • Urinalysis
  • Allergy/rash (immediate or delayed)
  • Cytopenias- esp. drug-induced thrombocytopenia
  • Eosinophilia
  • Delayed and immediate hypersensitivity reactions
  • Neurotoxicity
  • Nephrotoxicity
  • Myelosuppression
  • Interstitial nephritis
  • Abnormal liver enzymes
  • N/V/D and abdominal pain
  • Headache
  • Increases levels of methotrexate
  • Decreases levels of mycophenolate
  • Inactivation of aminoglycosides
  • Probenecid can increase levels of Zosyn

Antimicrobial class: Ureidopenicillin with a beta-lactamase inhibitor

Pregnancy category: B

Average serum half life: 0.7-1.2 hour

  • Neonatal half life: 1.7-8.9 hours

Biliary penetration: Therapeutic

CSF penetration: Poor especially with noninflamed meninges

Lung penetration: Therapeutic

Urine penetration: Therapeutic

Dosing per AHSM Extended Infusion/Alternative Dosing of Antibiotics Protocol


  • Patients not being admitted (i.e. Emergency Department)
  • One-time pre-operative surgery dosing
  • Medication incompatibility problems upon initiation of therapy or after. A pharmacist must review these medications and determine if patient is unable to utilize protocol dosing
  • Patients < 17 y.o. and under the minimum weight
  • Pregnancy
  • Physician writes "Do Not Substitute"