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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 (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia
## Adult Dosing
Standard dosing is typically **4.5 g** (piperacillin 4 g / tazobactam 0.5 g) every 6 hours intravenously. Doses can be increased to **9 g** (piperacillin 8 g / tazobactam 1 g) every 8 hours intravenously for severe or life-threatening infections, or infections due to less susceptible organisms. Duration of therapy varies based on indication and clinical response, generally 4-14 days.
## Pediatric Dosing
Dosing is based on piperacillin component and varies by indication and patient weight.
* **2 to < 12 months:** 75 mg/kg (piperacillin component) every 8 hours.
* **1 to 12 years:** 75 mg/kg (piperacillin component) every 6 hours or 100 mg/kg (piperacillin component) every 8 hours.
Maximum pediatric doses are generally capped at the adult dose of 4.5 g per dose for typical indications, and up to 9 g per dose for severe infections. Specific dosing for neonates and infants requires careful consideration and adherence to institutional guidelines.
## Dose Adjustments
* **Renal Impairment:** Adjust dose based on creatinine clearance (CrCl).
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* Hemodialysis: Administer usual dose every 8 hours and supplement with an additional dose of 2.25 g after each dialysis session.
## Contraindications
* Known serious allergic reaction to penicillin, cephalosporins, beta-lactamase inhibitors, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hepatotoxicity, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** Piperacillin can potentially decrease warfarin's anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, CrCl).
* Liver function tests.
* Complete blood count (CBC) with differential and platelets, particularly with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
## Clinical Pearls
* Piperacillin/tazobactam has excellent activity against *Pseudomonas aeruginosa*.
* Dosing in critically ill patients may require higher doses and/or more frequent administration based on pharmacokinetic principles and local protocols, particularly for infections with high bacterial burdens or resistant organisms.
* Reconstituted solutions should be used within specified timeframes.
* Ensure adequate hydration to minimize risk of crystalluria.
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*This information is intended for healthcare professionals. Always verify current prescribing information with the official product monograph or other reliable sources.*
