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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) IV every 6 hours.
Common dose for more severe infections: 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) IV every 6 or 8 hours.
Maximum dose: Generally not to exceed 18 grams per day (16 grams piperacillin/2 grams tazobactam).
Duration of therapy depends on indication and clinical response.
## Pediatric Dosing
Dosing is based on piperacillin component. Consult specific guidelines or institutional protocols as pediatric dosing can vary significantly by indication and age/weight.
* **Intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours for children 3 months to 12 years.
* **Hospital-acquired pneumonia:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose IV every 6 hours for children 3 months to 12 years.
Dosing for neonates and infants < 3 months is complex and requires specific protocols.
## 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 IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours.
* For hemodialysis patients, administer a 2.25 gram dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, headache, rash, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT), increased creatinine.
* **Serious:** *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures (especially with high doses or renal impairment), interstitial nephritis, leukopenia, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Electrolytes.
* Signs and symptoms of infection (clinical response).
* Signs and symptoms of hypersensitivity reactions.
* INR if patient is on warfarin.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many beta-lactamases, broadening its spectrum of activity, particularly against Gram-negative aerobes and anaerobes.
* Ensure adequate hydration to minimize the risk of neurotoxicity.
* Infusion over at least 30 minutes is recommended to reduce the risk of infusion-related reactions.
* For indications like febrile neutropenia, therapy should be initiated promptly.
**Disclaimer:** This information is for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information or a qualified healthcare provider for definitive guidance.
