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# Piperacillin-Tazobactam
## 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, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
The typical dose is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 to 8 hours intravenously. Dosing frequency and duration depend on the indication and severity of infection, as well as the patient's clinical response. For severe infections or *Pseudomonas aeruginosa* infections, doses of 4.5 grams every 6 hours may be preferred. The maximum daily dose should not exceed 18 grams (16g piperacillin/2g tazobactam) per day.
## Pediatric Dosing
Dosing for pediatric patients varies by indication and age/weight.
* **Intra-abdominal infections (3 months to 12 years):** 90 mg piperacillin/11.25 mg tazobactam per kg per dose administered every 8 hours. Maximum dose: 3.375 grams per dose.
* **Complicated skin and skin structure infections (3 months to 12 years):** 90 mg piperacillin/11.25 mg tazobactam per kg per dose administered every 8 hours. Maximum dose: 3.375 grams per dose.
* **Nosocomial pneumonia (3 months to 12 years):** 90 mg piperacillin/11.25 mg tazobactam per kg per dose administered every 8 hours. Maximum dose: 3.375 grams per dose.
For children weighing > 50 kg, adult dosing should be used. For neonates and infants younger than 3 months, safety and efficacy have not been established.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased dosing interval is recommended based on creatinine clearance (CrCl).
* CrCl 20-40 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* For doses of 4.5 grams every 6 hours, adjust to 3.375 grams every 6 hours if CrCl is 20-40 mL/min, and 2.25 grams every 6 hours if CrCl is < 20 mL/min.
* Hemodialysis: Administer usual dose every 8 hours. Give an additional 0.75g dose after each hemodialysis session.
* **Hepatic Impairment:** No specific dose adjustments are typically recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and injection site reactions. Serious adverse effects include *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, and hematologic abnormalities.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for *Clostridioides difficile*-associated diarrhea.
* Monitor renal function, electrolytes, and complete blood counts, especially with prolonged therapy.
* Monitor liver function tests.
* Monitor INR if co-administered with warfarin.
## Clinical Pearls
* Piperacillin-tazobactam is often reconstituted and further diluted for IV infusion over 30 minutes. A 30-minute infusion is standard, but a 4-hour infusion may be used for doses of 4.5 grams in patients with *Pseudomonas aeruginosa* infections. Consult local protocols.
* The potential for cross-reactivity with cephalosporins exists in patients with penicillin allergy.
* Ensure adequate hydration to prevent crystalluria.
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*This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions. Dosing and recommendations may vary based on local protocols and individual patient factors.*
