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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination penicillin-type antibiotic and 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)
* Febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 8 hours.
* **Severe Infections/High Inoculum:** May require higher doses, such as 4.5 grams every 6 hours.
* **Maximum Dose:** Not clearly defined, but commonly dosed up to 4.5 grams every 6 hours. Dosing should be guided by institutional protocols and clinical response.
* **Duration:** Typically 7 to 14 days, depending on the indication and severity.
## Pediatric Dosing
* **Children 2 months and older:** Dosing varies based on indication and indication. A common starting point for uncomplicated infections is 90 mg/kg/day (as piperacillin) divided every 6 or 8 hours. For complicated infections or those requiring higher levels, doses up to 300 mg/kg/day (as piperacillin) divided every 6 or 8 hours have been used.
* **Maximum Pediatric Dose:** Generally not to exceed the adult maximum of 4 grams of piperacillin per dose.
* **Specific pediatric dosing is complex and highly dependent on indication, severity, and local protocols.** Consultation with pediatric infectious disease or pharmacy is recommended.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) IV every 8 hours or 3.375 grams IV every 12 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 12 hours.
* **Hemodialysis:** 2.25 grams IV every 8 hours, with an additional 0.75 grams dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is usually necessary.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, any other piperacillin/tazobactam formulation, or any of its components.
* History of immediate or severe allergic reaction to beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, elevated liver enzymes.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, neutropenia, thrombocytopenia, seizure (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:** Piperacillin may decrease the efficacy of warfarin, leading to an increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Complete blood count (CBC) for potential hematologic changes (neutropenia, thrombocytopenia).
* Electrolytes.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Clinical signs of infection resolution.
## Clinical Pearls
* Piperacillin-tazobactam is a large molecule and is not typically removed by hemodialysis, but the tazobactam component is. Therefore, an additional dose is recommended after hemodialysis.
* Tazobactam is a beta-lactamase inhibitor, extending the spectrum of piperacillin to include many beta-lactamase-producing organisms.
* Reconstituted solutions should be used within 24 hours when stored at room temperature or within 48 hours when refrigerated.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the current prescribing information and institutional protocols for the most up-to-date and comprehensive guidance before administering any medication.
