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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and a beta-lactamase inhibitor. It has broad-spectrum activity against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Common adult dosing is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. Dosing frequency and total daily dose depend on the severity and type of infection. Higher doses may be used for severe infections or documented resistance.
## Pediatric Dosing
Pediatric dosing varies by indication and weight.
* **Intra-abdominal infections, skin and skin structure infections, and community-acquired pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours for patients 2 months to 12 years of age.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours for patients 2 months to 12 years of age.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours for patients 2 months to 12 years of age.
* **Neonates and infants younger than 2 months:** Dosing is highly variable and depends on gestational and postnatal age; consult specific pediatric guidelines.
Maximum dose is typically 4.5 grams every 6 or 8 hours, but may be higher in specific circumstances per institutional guidelines.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased dosing interval is required for creatinine clearance less than 40 mL/min.
* CrCl 20-40 mL/min: Reduce dose by 25%.
* CrCl < 20 mL/min: Reduce dose by 50% and/or increase interval to every 8-12 hours.
* Hemodialysis: Administer dose after dialysis and supplement with an additional 2.25g dose every 8 hours.
## Contraindications
* Hypersensitivity to piperacillin, other penicillin derivatives, tazobactam, or any component of the formulation.
* History of severe allergic reaction (e.g., anaphylaxis) to beta-lactam antibiotics.
## Adverse Effects
Common adverse effects include diarrhea, rash, nausea, vomiting, headache, insomnia, and eosinophilia. Serious adverse effects include C. difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), and hematologic changes (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** Increases and prolongs piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect; monitor INR closely.
* **Aminoglycosides:** While often used together, co-administration can lead to physical inactivation of piperacillin/tazobactam if mixed in the same IV bag or line; separate administration.
## Monitoring
* Renal function (creatinine clearance)
* Electrolytes
* Liver function tests
* Complete blood count (especially for prolonged therapy)
* Signs and symptoms of infection
* Signs of hypersensitivity reactions
## Clinical Pearls
* Reconstituted solution should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Piperacillin/tazobactam is typically administered as a continuous infusion or intermittent infusion over 30 minutes. Continuous infusions may achieve higher drug concentrations and reduce the risk of adverse effects. Dosing for continuous infusion often uses a higher total daily dose (e.g., 15g piperacillin/1.875g tazobactam over 24 hours).
* The risk of seizures is increased in patients with renal impairment and those receiving high doses.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and institutional protocols for the most up-to-date and complete drug information.*
