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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. It is active against a broad spectrum of gram-positive and gram-negative bacteria, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
* **Standard Dose:** 3.375 grams intravenously every 6 hours or 4.5 grams intravenously every 8 hours.
* **Higher Doses for Severe Infections (e.g., *Pseudomonas*):** 4.5 grams intravenously every 6 hours or 4.5 grams every 8 hours for critical illness. Actual dosing for severe infections may vary based on specific pathogens and clinical judgment and may require extended or continuous infusions.
* **Maximum Dose:** Typically not to exceed 4.5 grams per dose given every 6 hours.
## Pediatric Dosing
* **Children younger than 12 years:** Dosing is based on piperacillin component weight-based and typically ranges from 80 mg/kg/day to 300 mg/kg/day, divided every 6 or 8 hours, depending on the indication and severity of infection. The maximum daily dose should not exceed 16 grams of piperacillin. Refer to specific pediatric guidelines for precise dosing by indication.
* **Children 12 years and older:** Dosed as adults (3.375 grams IV q6h or 4.5 grams IV q8h).
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams IV every 6 hours or 3.375 grams IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours.
* Consider increasing dose frequency or maintaining higher doses for severe infections in hemodialysis patients, as doses are removed by dialysis.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or other components of the formulation.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may reduce methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially in patients with pre-existing renal impairment or those on nephrotoxic agents).
* Liver function tests.
* Complete blood count (CBC) with differential and platelet count.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
## Clinical Pearls
* Consider using extended or continuous infusion for severe infections or in critically ill patients, particularly those with *Pseudomonas aeruginosa*, to achieve higher and more sustained drug concentrations.
* Reconstituted solution should be used within 24 hours if stored at room temperature or within 48 hours if refrigerated.
* Monitor for signs of dehydration and electrolyte imbalance, especially with diarrhea.
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***Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for complete details before administering any medication.*
