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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a penicillinase-resistant penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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
## Adult Dosing
Standard dosing is 3.375 g (piperacillin 3 g/tazobactam 0.375 g) or 4.5 g (piperacillin 4 g/tazobactam 0.5 g) intravenously every 6 or 8 hours. Duration of therapy depends on the indication and clinical response, typically 7-14 days. The maximum daily dose is generally considered to be 18 g (piperacillin 16 g/tazobactam 2 g) divided into doses. Specific dosing for different indications may vary based on local protocols and severity of infection.
## Pediatric Dosing
Dosing for pediatric patients is typically based on the piperacillin component.
* **Patients ≥ 12 years:** Same as adult dosing.
* **Patients < 12 years:** Dosing varies by indication. Common ranges include 80-100 mg piperacillin/kg/day divided every 6 or 8 hours. For example, 100 mg piperacillin/kg/dose every 8 hours is often used for serious infections.
* **Neonates and Infants < 4 weeks or weighing < 50 kg:** Dosing is more complex and often weight-based, with consideration for gestational and chronological age. It is crucial to consult specific pediatric guidelines or institutional protocols.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or extension of interval is recommended.
* CrCl 20-40 mL/min: Reduce dose by 25%.
* CrCl < 20 mL/min: Reduce dose by 50% and/or increase interval to every 8 hours.
* Hemodialysis: Administer usual dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of severe allergic reactions to beta-lactam antibiotics.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and phlebitis at the injection site. Serious adverse effects include *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (particularly with high doses or renal impairment), neutropenia, and thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count (CBC) for hematologic changes (e.g., neutropenia, thrombocytopenia).
* Electrolytes.
* Signs and symptoms of infection for therapeutic response.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Dosing and duration are highly dependent on the specific infection, pathogen susceptibility, and patient factors.
* Piperacillin/tazobactam is often considered a broad-spectrum agent for empiric therapy of serious infections, including those involving *Pseudomonas aeruginosa*.
* The reconstituted solution is typically administered as an intravenous infusion over 30 minutes.
* Monitor for signs of superinfection with resistant organisms, especially with prolonged therapy.
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*This information is intended for clinical pharmacists and prescribers. Always verify current prescribing information, institutional protocols, and guidelines before making treatment decisions.*
