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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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
* Febrile neutropenia (empiric treatment)
## Adult Dosing
The typical dose is **3.375 grams every 6 hours** or **4.5 grams every 6 or 8 hours** administered intravenously. The specific ratio of piperacillin to tazobactam is usually 8:1. Higher doses may be used for severe infections or *Pseudomonas* infections. Dosing and frequency depend on the indication and severity of infection. Consult institutional guidelines for specific protocols.
## Pediatric Dosing
Dosing for pediatric patients varies significantly by age, weight, and indication.
* **3 months and older:**
* **Complicated intra-abdominal infections:** Doses range from 90 to 100 mg of piperacillin component per kg per dose, administered every 6 or 8 hours. Maximum dose is 4.5 grams per dose.
* **Hospital-acquired pneumonia and febrile neutropenia:** Doses range from 90 to 100 mg of piperacillin component per kg per dose, administered every 6 or 8 hours. Maximum dose is 4.5 grams per dose.
**Note:** Neonates and infants younger than 3 months have immature renal function, requiring specific dosing adjustments and potentially different frequency. Refer to specific pediatric guidelines or drug formularies for precise dosing in this population.
## Dose Adjustments
**Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: Administer the standard dose every 8 hours.
* CrCl < 20 mL/min: Administer standard dose every 12 hours.
* Hemodialysis: Administer standard dose every 12 hours and an additional 1.125 g dose after each dialysis session.
**Hepatic Impairment:** Dose adjustment is generally not required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, pruritus, and elevated liver enzymes. Serious adverse effects include *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), and seizures.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin-tazobactam levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant 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 diarrhea and signs of *C. difficile*-associated diarrhea.
* Renal and hepatic function tests may be warranted, especially with prolonged therapy or in patients with pre-existing impairment.
* Monitor electrolytes, particularly if given with other nephrotoxic agents or diuretics.
## Clinical Pearls
* Piperacillin-tazobactam can be reconstituted with sterile water for injection or sodium chloride 0.9%.
* Further dilution in compatible IV fluids (e.g., NaCl 0.9%, D5W) is required for infusion.
* Infusion should be over at least 30 minutes to reduce the risk of infusion-related reactions.
* Ensure adequate hydration to minimize the risk of crystalluria, especially with high doses.
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**Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. Always consult the most current prescribing information and institutional protocols for definitive dosing, administration, and safety guidance.
