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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and beta-lactamase inhibitor. It has broad-spectrum activity against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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 grams (piperacillin 3 g/tazobactam 0.375 g) every 6 hours or 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) every 6 or 8 hours. Dosing and frequency depend on the severity and type of infection, as well as patient factors. Higher doses (e.g., 3.375 g every 4 hours or 4.5 g every 6 hours) may be used for severe infections or *Pseudomonas aeruginosa* infections.
## Pediatric Dosing
For pediatric patients (age 3 months to 12 years), dosing is typically based on piperacillin weight.
* **Complicated intra-abdominal infections:** 90 mg/kg (piperacillin component) every 8 hours.
* **Hospital-acquired pneumonia:** 90 mg/kg (piperacillin component) every 8 hours.
* **Febrile neutropenia:** 90 mg/kg (piperacillin component) every 6 hours.
Maximum dose is typically 4.5 grams per dose for non-neutropenic pediatric patients and 3.375 grams per dose for neutropenic pediatric patients. Dosing in neonates and infants less than 3 months is less established and should be based on institutional guidelines.
## Dose Adjustments
**Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose by 25% or increase interval to every 8 hours.
* CrCl < 20 mL/min: Reduce dose by 50% or increase interval to every 8-12 hours.
* Hemodialysis: Give dose every 8 hours and administer an additional dose of 2.25 grams after each dialysis session.
**Hepatic Impairment:** No dose adjustment is typically recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, particularly with high doses or renal impairment), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents:** May prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function
* Liver function tests
* Complete blood count (CBC) with differential, especially with prolonged therapy
* Signs and symptoms of infection resolution
* *Clostridioides difficile* testing if diarrhea develops
## Clinical Pearls
* Reconstitute and dilute according to manufacturer instructions.
* Administer over at least 30 minutes.
* Consider de-escalation to narrower-spectrum agents once culture and sensitivity results are available.
* Tazobactam is primarily to protect piperacillin from beta-lactamase degradation; it has minimal intrinsic antibacterial activity.
* The risk of seizures may be increased in patients with renal impairment or those receiving high doses.
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**Disclaimer:** This information is intended for clinical decision support and does not replace the official prescribing information or professional judgment. Always verify current prescribing information and institutional protocols.
