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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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 (empiric treatment)
* Various other serious infections caused by susceptible organisms.
## Adult Dosing
The typical dose is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) administered intravenously every 6 to 8 hours.
* For severe infections or *Pseudomonas aeruginosa* infections, doses may be increased to 4.5 grams every 6 hours, or extended infusions of 3.375 grams or 4.5 grams over 4 hours every 6 hours may be used.
* Maximum daily dose is generally 18 grams (16g piperacillin/2g tazobactam) given as 4.5 grams every 6 hours. Dosing depends heavily on the indication and severity of illness. Consult institutional guidelines.
## Pediatric Dosing
* **Patients 2 months and older:** Dosing is typically based on piperacillin weight-based recommendations.
* **2 months to 12 years:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered intravenously every 8 hours.
* **12 years and older:** Doses are the same as adults (e.g., 3.375 g or 4.5 g every 6-8 hours).
* **For *Pseudomonas aeruginosa* or severe infections:** Doses can be increased to 150 mg piperacillin/18.75 mg tazobactam per kg per dose administered intravenously every 6 hours, not to exceed 4.5 grams per dose.
* Dosing in neonates and infants younger than 2 months is not well established due to immature renal function. Consult specialized pediatric resources.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer the usual dose every 8 hours.
* CrCl < 20 mL/min: Administer two-thirds of the usual dose every 8 hours.
* For patients on intermittent hemodialysis, administer the usual dose every 8 hours, and give an additional dose of two-thirds the usual dose after each dialysis session.
* **Hepatic Impairment:** No specific guidelines, but piperacillin is primarily cleared renally. Monitor for efficacy and toxicity.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to amoxicillin, ampicillin, piperacillin, or piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic changes (e.g., neutropenia, thrombocytopenia), liver enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin, increasing serum concentrations and risk of toxicity.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's effect; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, increasing toxicity.
## Monitoring
* Renal function (baseline and during therapy).
* Liver function tests.
* Complete blood count (especially with prolonged therapy for potential hematologic changes).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* Electrolytes.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often reserved for more serious infections or when resistance to narrower-spectrum agents is suspected.
* The duration of therapy should be guided by the clinical response and the specific infection.
* Ensure adequate hydration to minimize the risk of crystalluria.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours if refrigerated. Check manufacturer's instructions.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines for complete details.
