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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
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3 g piperacillin/0.375 g tazobactam) or 4.5 grams (4 g piperacillin/0.5 g tazobactam) intravenously every 6 or 8 hours.
* **Higher Dosing (e.g., severe infections, pseudomonas coverage):** 4.5 grams intravenously every 6 or 8 hours. Higher doses may be used based on institutional guidelines and susceptibility data.
* **Maximum Dose:** Not clearly defined, but doses up to 4.5 grams every 6 hours are common.
## Pediatric Dosing
Dosing varies by indication, age, and weight. Consult specific pediatric guidelines or institutional protocols. General guidelines:
* **Neonates and Infants (up to 12 months):** Dosing is complex and often based on piperacillin component (e.g., 50-100 mg piperacillin per kg per dose IV every 8-12 hours, with tazobactam dose adjusted accordingly).
* **Children (1 to 12 years):** 90-100 mg piperacillin per kg per dose (equivalent to 80-90 mg piperacillin/10-11.25 mg tazobactam per kg per dose) IV every 6 or 8 hours. Do not exceed adult doses.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Reduce dose by 25% or increase dosing interval to every 8 hours.
* CrCl < 20 mL/min: Reduce dose by 50% or increase dosing interval to every 8 hours.
* **Hemodialysis:** Administer dose after dialysis and increase dosing interval to every 8 hours. An additional 1 g of piperacillin component should be given after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known history of severe allergic reaction to piperacillin, tazobactam, other penicillin antibiotics, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, constipation.
* **Serious:** Hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, hepatotoxicity.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (serum creatinine, BUN).
* Liver function tests (AST, ALT).
* Complete blood count (CBC) for potential hematologic changes.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Therapeutic drug monitoring is generally not required but may be considered in specific situations (e.g., critical illness, altered pharmacokinetics).
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against Pseudomonas aeruginosa.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours if at room temperature.
* Ensure adequate hydration to minimize the risk of crystalluria.
* Monitor for signs of superinfection.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for clinical judgment. Always refer to the most current prescribing information and institutional protocols before administering any medication.
