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# Piperacillin-tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is an extended-spectrum penicillin antibiotic combined with 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 Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours intravenously (IV).
* **Higher Dosing (e.g., severe infections, hospital-acquired pneumonia, febrile neutropenia):** May use 4.5 grams every 6 or 8 hours IV. Some protocols may utilize continuous infusion for critically ill patients, with a loading dose followed by a continuous infusion. Specific protocols vary.
* **Maximum Daily Dose:** Generally not to exceed 18 grams per day (4.5g every 6 hours).
## Pediatric Dosing
* **Age < 12 years:** Dosing varies based on indication and weight.
* **Intra-abdominal infections:** 90 mg piperacillin component/11.25 mg tazobactam component per kg per dose every 6 hours IV.
* **Hospital-acquired pneumonia:** 90 mg piperacillin component/11.25 mg tazobactam component per kg per dose every 6 hours IV.
* **Age ≥ 12 years:** Same as adult dosing.
* **Maximum Pediatric Dose:** Should not exceed the maximum adult dose.
* **Neonates:** Dosing and frequency are complex and depend on gestational and postnatal age. Consult specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: Reduce dose frequency to every 8 hours (for 6-hour interval regimens) or every 12 hours (for 8-hour interval regimens).
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours (for 6-hour interval regimens) or every 12 hours (for 8-hour interval regimens). Consider further dose reduction or increased interval based on clinical response and local protocols.
* **Hepatic Impairment:** No specific guidelines; use with caution.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to penicillin or beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, eosinophilia, elevated AST/ALT.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin and increase serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may reduce the clearance of methotrexate. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (especially with prolonged therapy).
* Signs and symptoms of infection.
* Electrolytes, especially in patients with renal impairment or receiving large fluid volumes.
* INR if co-administered with warfarin.
* Signs of hypersensitivity reactions.
## Clinical Pearls
* Piperacillin-tazobactam has broad-spectrum activity, including against *Pseudomonas aeruginosa*.
* Dosing frequency and route (intermittent vs. continuous infusion) can impact efficacy and safety, especially in critically ill patients. Consult institutional guidelines.
* The beta-lactamase inhibitor tazobactam protects piperacillin from degradation by many bacterial beta-lactamases.
* Discontinue if hypersensitivity reactions occur.
* Monitor for *C. difficile* infection.
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*Please verify current prescribing information for the most up-to-date details.*
