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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active 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 dosing is typically 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 to 8 hours.
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections, Community-Acquired Pneumonia:** 3.375 grams IV every 6 hours OR 4.5 grams IV every 8 hours.
* **Nosocomial Pneumonia:** 3.375 grams IV every 6 hours OR 4.5 grams IV every 8 hours. Consider higher doses (e.g., 4.5 grams IV every 6 hours) for patients with risk factors for infection with resistant organisms.
* **Febrile Neutropenia:** 4.5 grams IV every 6 hours.
Duration of therapy is typically 7 to 14 days depending on the indication and clinical response.
## Pediatric Dosing
Dosing is based on piperacillin content.
* **3 months and older:**
* Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, and nosocomial pneumonia:
* **Mild to moderate:** 90-100 mg piperacillin/12.5-15 mg tazobactam per kg per dose IV every 6 hours.
* **Severe:** 90-100 mg piperacillin/12.5-15 mg tazobactam per kg per dose IV every 6 hours. Maximum dose of 4.5 grams per dose.
* Febrile neutropenia: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours. Maximum dose of 4.5 grams per dose.
* **Note:** Specific maximum doses per administration vary by institution. Dosing for neonates and infants under 3 months is not well-established and should be guided by institutional protocols.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: 2.25 grams IV every 6 hours (or 4.5 grams IV every 8 hours for higher dose regimens).
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours (or 4.5 grams IV every 12 hours for higher dose regimens).
* Hemodialysis: 2.25 grams IV every 8 hours, with an additional 0.75 grams dose after each hemodialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but monitor closely.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, insomnia, headache, fever, eosinophilia.
* **Serious:**
* Hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome, DRESS).
* Clostridioides difficile-associated diarrhea (CDAD).
* Seizures (especially with high doses or renal impairment).
* Hepatotoxicity.
* Neutropenia, thrombocytopenia, anemia.
* Interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin, increasing serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin, leading to reduced INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, increasing toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, BUN) for dose adjustments.
* Liver function tests (AST, ALT, bilirubin) periodically.
* Complete blood count (CBC) with differential and platelets, especially with prolonged therapy or suspected hematologic toxicity.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Piperacillin/tazobactam is administered as a continuous infusion or intermittent IV infusion. Consult institutional guidelines for specific infusion rates and durations.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours at room temperature.
* The beta-lactamase inhibitor, tazobactam, extends the spectrum of activity of piperacillin to include many beta-lactamase-producing bacteria.
* Ensure adequate hydration to minimize the risk of crystalluria.
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**Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the official prescribing information and institutional protocols for the most current and complete guidance. Always verify drug information before administration.
