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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a penicillin-class antibiotic combined with a beta-lactamase inhibitor. It has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose is 3.375 g every 6 hours intravenously (IV).
High-dose regimens for severe infections or nosocomial pneumonia may include 4.5 g every 6 hours IV.
Doses are typically administered over 30 minutes. Prolonged infusions (e.g., 4 hours) may be used for some indications to achieve higher drug concentrations. Specific protocols should be consulted.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Children > 2 months:** 90 mg/kg (piperacillin component) every 8 hours IV.
* **Children > 2 months with severe infections or nosocomial pneumonia:** 112.5 mg/kg (piperacillin component) every 6 hours IV.
Maximum dose per administration is typically 4.5 g piperacillin. Consult institutional guidelines for exact weight-based dosing and infusion strategies in neonates and infants.
## Dose Adjustments
**Renal Impairment (CrCl < 40 mL/min):**
* **3.375 g every 6 hours:** Reduce to 2.25 g every 6 hours.
* **4.5 g every 6 hours:** Reduce to 3.375 g every 6 hours.
Dosing frequency may need further adjustment in severe renal failure or with hemodialysis.
**Hepatic Impairment:** No dose adjustment is typically recommended.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, or penicillins.
* History of allergic reaction to cephalosporins or other beta-lactams.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, fever, insomnia.
Serious: Clostridioides difficile-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic changes (leukopenia, neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May decrease renal clearance of piperacillin/tazobactam, leading to increased serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of neuromuscular blocking agents.
* **Warfarin:** Piperacillin may decrease serum concentrations of warfarin, potentially reducing INR. Monitor INR closely.
* **Live attenuated bacterial vaccines:** May reduce the efficacy of the vaccine.
## Monitoring
* Signs and symptoms of infection.
* Renal function (BUN, creatinine).
* Electrolytes.
* Liver function tests.
* Complete blood count (especially if prolonged therapy).
* Signs of hypersensitivity reactions.
* Clostridioides difficile infection.
## Clinical Pearls
* Piperacillin/tazobactam has significant activity against Pseudomonas aeruginosa.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing bacteria.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated. Consult manufacturer guidelines.
* Monitor for signs of superinfection, including fungal infections.
* Sodium content: Each gram of piperacillin/tazobactam contains approximately 2.05 mmol (47 mg) of sodium. Consider in patients on sodium-restricted diets.
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*This information is for educational purposes and does not substitute for current prescribing information or clinical judgment. Always verify with the most recent drug monograph and institutional guidelines.*
