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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin antibiotic and 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
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours. Doses are expressed as the piperacillin component (e.g., 3g piperacillin/0.375g tazobactam or 4g piperacillin/0.5g tazobactam).
Maximum dose: Generally limited by administration volume and patient's renal/hepatic function. Higher doses, such as 4.5 grams IV every 6 hours, may be used for severe infections.
## Pediatric Dosing
Dosing is based on the piperacillin component.
* **3 months to 12 years:** 90 to 100 mg piperacillin per kg per dose IV every 6 or 8 hours. Maximum dose not to exceed 4 grams per dose.
* **12 years and older:** Dosing typically follows adult recommendations.
* **Neonates and infants < 3 months:** Dosing is complex and depends on gestational and postnatal age. Consult specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment.
* CrCl 20-40 mL/min: 2.25 grams IV every 6 hours or 3.375 grams IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours or 3.375 grams IV every 12 hours.
* Doses for pediatric patients will also require adjustment.
* **Hepatic Impairment:** No specific dose adjustment, but monitor closely for adverse effects.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* Diarrhea (most common)
* Rash, pruritus
* Nausea, vomiting
* Headache
* Fever
* Eosinophilia
* Thrombocytopenia, neutropenia, leukopenia (more common with prolonged therapy)
* Increased serum creatinine and BUN
* *Clostridioides difficile*-associated diarrhea
* Seizures (especially with high doses or renal impairment)
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (serum creatinine, BUN)
* Electrolytes
* Complete blood count (CBC), especially with prolonged therapy
* Liver function tests
* Signs and symptoms of infection
* Signs of hypersensitivity reactions
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often reserved for more serious infections or when resistance to other agents is suspected.
* Reconstituted solutions should be administered promptly. Stability varies with diluent.
* Infusion-related adverse events (e.g., phlebitis) can occur; consider using a central venous catheter for prolonged infusions.
* The 4.5 g formulation offers a higher piperacillin-to-tazobactam ratio and may be preferred in certain situations (e.g., *Pseudomonas aeruginosa* infections).
* Consult local antibiograms for resistance patterns.
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*This information is intended for healthcare professionals. Always verify current prescribing information and consult relevant guidelines before making treatment decisions.*
