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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic 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
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
Standard dose: 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) intravenously every 6 hours.
Higher dose: 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) intravenously every 6 or 8 hours.
* Dosing frequency and duration depend on the indication, severity of infection, and pathogen susceptibility.
* Maximum daily dose typically does not exceed 18 grams (16 grams piperacillin/2 grams tazobactam).
## Pediatric Dosing
Dosing is based on piperacillin component. Recommended doses vary by indication and patient weight.
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours for patients < 2 months. For patients ≥ 2 months, 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 6 or 8 hours, not to exceed 4 grams piperacillin/0.5 grams tazobactam per dose.
* **Hospital-acquired pneumonia:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose intravenously every 6 hours for patients ≥ 2 months, not to exceed 4 grams piperacillin/0.5 grams tazobactam per dose.
* Consult specific pediatric guidelines for precise dosing and adjustments for age and weight.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) IV every 6 hours or 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) IV every 8 hours.
* Hemodialysis: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) IV every 8 hours, plus an additional 0.75 grams (0.67 grams piperacillin/0.08 grams tazobactam) dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known history of severe allergic reaction to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* Most common: Diarrhea, nausea, vomiting, rash, headache, insomnia.
* Serious: Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, neutropenia, thrombocytopenia, seizures (especially with high doses or renal impairment), interstitial nephritis.
## 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 efficacy of warfarin; increased INR monitoring is recommended.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, BUN)
* Electrolytes
* Liver function tests
* Complete blood count (CBC), especially if prolonged therapy or risk factors for hematologic toxicity.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Reconstitute and dilute per manufacturer instructions. Administer as a slow intravenous infusion over at least 30 minutes.
* Ensure adequate hydration to minimize the risk of crystalluria.
* Monitor for signs of C. difficile-associated diarrhea.
* Be aware of the potential for false-positive results with certain urine glucose tests.
* Piperacillin/tazobactam has activity against *Pseudomonas aeruginosa*.
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*Disclaimer: This information is intended for healthcare professionals and should not replace professional medical advice. Always consult the most current prescribing information and institutional guidelines before administering any medication.*
