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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, 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 (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV).
* **Higher Dose (for severe infections, e.g., HAP/VAP, febrile neutropenia):** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV. Dosing every 8 hours may be preferred for critically ill patients to achieve higher trough concentrations.
Duration of therapy typically ranges from 4 to 14 days, depending on the infection and clinical response.
## Pediatric Dosing
* **Children 1 month to 12 years:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight per dose, administered every 8 hours IV.
* **Children > 12 years:** Same as adult dosing.
* **Neonates (< 1 month):** Dosing is less established and should be guided by institutional protocols or expert consultation, often based on weight and gestational age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer the recommended dose every 8 hours.
* CrCl < 20 mL/min: Administer one-half of the recommended dose every 8 hours, or one-third of the recommended dose every 12 hours.
* Hemodialysis: Administer one-half of the recommended dose every 8 hours. An additional dose of one-half the recommended dose should be given after each hemodialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, constipation.
* **Serious:** Hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), liver enzyme elevations, hematologic changes (neutropenia, thrombocytopenia, eosinophilia).
## 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 effectiveness of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count, including platelet count.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Electrolytes.
## Clinical Pearls
* The 3.375g dose contains 3g piperacillin and 0.375g tazobactam. The 4.5g dose contains 4g piperacillin and 0.5g tazobactam.
* Reconstituted solution should be infused over at least 30 minutes.
* Monitor for signs of superinfection, especially in patients on prolonged therapy.
* Can be reconstituted with sterile water for injection, 0.9% sodium chloride, or dextrose 5% injection. Check compatibility with other IV medications.
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*Disclaimer: This information is intended for clinical decision-making support and does not replace professional judgment or current prescribing information. Always consult the official product monograph or other reliable sources for complete and up-to-date information before administering any medication.*
