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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal and has activity against many Gram-positive, Gram-negative, and anaerobic bacteria, including *Pseudomonas aeruginosa*.
## 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 dose is 3.375 g every 6 hours or 4.5 g every 6 or 8 hours administered intravenously (IV). Dosing is based on piperacillin component. The 3.375 g dose contains 3 g piperacillin and 0.375 g tazobactam. The 4.5 g dose contains 4 g piperacillin and 0.5 g tazobactam. Specific dose and frequency may depend on the severity of infection and local institutional protocols.
## Pediatric Dosing
* **Intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, hospital-acquired pneumonia:**
* 3 months to < 2 years: 90 mg/kg (piperacillin component) IV every 8 hours.
* ≥ 2 years: 90 mg/kg (piperacillin component) IV every 6 hours.
* Maximum dose: 4.5 g per dose.
* **Febrile neutropenia:**
* 6 months to < 12 years: 100 mg/kg (piperacillin component) IV every 8 hours.
* ≥ 12 years: 3.375 g IV every 6 hours or 4.5 g IV every 6 or 8 hours.
* Maximum dose: 4.5 g per dose.
Dosing in neonates and infants < 3 months is not established.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: 2.25 g (piperacillin) every 6 hours or 3.375 g (piperacillin) every 8 hours.
* CrCl < 20 mL/min: 2.25 g (piperacillin) every 8 hours or 3.375 g (piperacillin) every 12 hours.
* Hemodialysis: Administer dose after dialysis and supplement with an additional dose.
Consider dose adjustments for pediatric patients based on CrCl.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain, fever.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis, hepatic dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Aminoglycosides:** Consider additive or synergistic effects, but also potential antagonism; separate administration if possible.
* **Warfarin:** May decrease warfarin effect; increased monitoring of INR is recommended.
* **Neuromuscular Blocking Agents:** Penicillins may prolong the action of neuromuscular blocking agents.
* **Methotrexate:** Piperacillin may reduce methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically, especially with dose adjustments).
* Liver function tests (periodically).
* Complete blood count (periodically, especially with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* For patients on warfarin, monitor INR closely.
## Clinical Pearls
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours under refrigeration. Further dilution for IV infusion is typically done in 0.9% Sodium Chloride or 5% Dextrose.
* Administer IV infusion over at least 30 minutes to minimize infusion-related reactions.
* Tazobactam component protects piperacillin from degradation by many beta-lactamase enzymes, extending its spectrum of activity.
* Consider de-escalation based on culture and sensitivity results when appropriate.
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**Disclaimer:** This information is intended for educational purposes only and does not substitute for professional medical advice. Always consult with a qualified healthcare provider and refer to the current prescribing information for the most up-to-date and comprehensive details regarding drug use, safety, and indications.
