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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
Standard dose is 3.375 g or 4.5 g IV every 6 or 8 hours. Duration varies by indication, typically 7-14 days. Higher doses may be used for severe infections or critically ill patients, often guided by susceptibility testing and local protocols.
## Pediatric Dosing
* **Infants and children (up to 12 years):** Dosing is based on piperacillin component. Typical doses range from 100 mg/kg/day piperacillin to 300 mg/kg/day piperacillin, divided every 6 to 8 hours. The corresponding tazobactam dose is 12.5 mg/kg/day piperacillin to 37.5 mg/kg/day piperacillin. Maximum pediatric dose of piperacillin is 4 g per dose (equivalent to 4.5 g of the combination product).
* **Adolescents (12 years and older):** Dosing typically follows adult recommendations based on weight (e.g., 50 mg/kg piperacillin, max 4.5 g per dose).
* **Neonates:** Dosing is complex and highly dependent on gestational and postnatal age, often requiring specialized consultation.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose by 25% or increase interval to 8 hours.
* CrCl < 20 mL/min: Reduce dose by 50% or increase interval to 8-12 hours.
* Hemodialysis: Dose every 8 hours with a supplemental dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever.
Serious: Clostridioides difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), hematologic abnormalities (neutropenia, thrombocytopenia), hepatotoxicity.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Monitor INR closely as beta-lactams can potentially alter the anticoagulant effect.
## Monitoring
* Renal function.
* Liver function tests.
* Complete blood count (especially in prolonged therapy).
* Signs and symptoms of hypersensitivity.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Dosing frequency (every 6 vs. 8 hours) may depend on severity of infection, specific pathogen, and institutional guidelines. Continuous infusion may be considered in critically ill patients to maintain target drug concentrations.
* Reconstituted solutions should be used promptly. Discard unused portions.
* Ensure adequate hydration in patients receiving high doses to minimize risk of crystalluria.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering this medication.
