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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It provides 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 is **3.375 g** (3 g piperacillin/0.375 g tazobactam) every **6 hours** intravenously (IV).
Higher doses of **4.5 g** (4 g piperacillin/0.5 g tazobactam) every **6 hours** IV are often used for more severe infections, hospital-acquired pneumonia, or when treating *Pseudomonas aeruginosa*.
Continuous infusion regimens are also used, typically a **13.5 g** (12 g piperacillin/1.5 g tazobactam) per 24-hour period administered as a loading dose of **4.5 g** followed by a continuous infusion of **9 g** every 24 hours.
Dosing frequency and duration are guided by infection severity, pathogen susceptibility, and clinical response.
## Pediatric Dosing
Dosing varies by indication and patient weight.
For patients **≥ 2 months of age**:
* **Intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia**: Typically **90 mg/kg/dose** (80 mg piperacillin/10 mg tazobactam) every **6 hours** IV.
* **Hospital-acquired pneumonia, febrile neutropenia**: Typically **112.5 mg/kg/dose** (100 mg piperacillin/12.5 mg tazobactam) every **6 hours** IV.
Maximum single dose should not exceed the adult dose of 4.5 g.
Dosing should be adjusted based on the severity of illness.
## Dose Adjustments
**Renal Impairment**:
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: **3.375 g** every **8 hours** (or **4.5 g** every **8 hours** for higher doses).
* CrCl < 20 mL/min: **2.25 g** every **8 hours** (or **3.375 g** every **8 hours** for higher doses).
* For continuous infusion: Reduce the continuous rate by 50%.
Hemodialysis requires further dose adjustments.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, beta-lactamase inhibitors, or any component of the formulation.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
Most common: Diarrhea, rash, nausea, vomiting, headache, insomnia.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, especially with high doses or renal impairment), neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid**: May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Warfarin**: May decrease the effect of warfarin; requires increased INR monitoring.
* **Neuromuscular blocking agents (e.g., vecuronium)**: Piperacillin may prolong the neuromuscular blockade.
* **Methotrexate**: May decrease methotrexate clearance and increase toxicity; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests (AST, ALT, bilirubin).
* Complete blood count (CBC) for potential hematologic changes (neutropenia, thrombocytopenia).
* Signs and symptoms of infection for efficacy.
* Signs and symptoms of hypersensitivity reactions.
* INR if patient is on warfarin.
## Clinical Pearls
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours if refrigerated.
* Dosing and duration of therapy should be guided by institutional protocols and clinical response, especially for complex infections or resistant organisms.
* Monitor for signs of *Clostridioides difficile* infection.
* When used for febrile neutropenia, continue until neutropenia resolves and fever has been absent for at least 48 hours.
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**Disclaimer**: This information is intended for healthcare professionals. Always consult the official prescribing information and current clinical guidelines for definitive recommendations. Drug information can change rapidly.
