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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. The addition of tazobactam extends the spectrum of activity of piperacillin to include many beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
Standard dose is 3.375 grams (piperacillin 3g/tazobactam 0.375g) every 6 hours intravenously.
Higher doses may be used for severe infections, including 4.5 grams (piperacillin 4g/tazobactam 0.5g) every 6 or 8 hours intravenously.
Maximum daily dose for adults is typically 18 grams (piperacillin 16g/tazobactam 2g). Duration of therapy is generally 7 to 14 days.
## Pediatric Dosing
For patients 2 months of age and older:
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered intravenously every 8 hours.
* **Nosocomial pneumonia:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose administered intravenously every 6 hours.
* Maximum dose: Do not exceed the adult maximum dose of 4.5 g per dose.
Dosing should be adjusted based on the severity of illness and renal function.
## Dose Adjustments
**Renal Impairment:**
* CrCl 50-80 mL/min: 3.375 g every 8 hours.
* CrCl 20-50 mL/min: 2.25 g every 8 hours.
* CrCl <20 mL/min: 2.25 g every 12 hours.
* Hemodialysis: 2.25 g every 8 hours, plus an additional dose of 0.75 g after each dialysis session.
Doses are typically adjusted by reducing the dose or extending the interval.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other piperacillin/tazobactam formulations, or beta-lactams.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, fever, elevated liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, drug reaction with eosinophilia and systemic symptoms (DRESS).
## Key Drug Interactions
* **Probenecid:** Increases piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate levels. Monitor methotrexate levels.
* **Live attenuated bacterial vaccines:** May decrease efficacy.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count (CBC) for signs of hematologic toxicity, particularly with prolonged therapy.
* Electrolytes, especially in patients with renal impairment.
* Signs and symptoms of infection.
* For *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours under refrigeration.
* Ensure adequate hydration to minimize risk of crystalluria.
* Monitor for signs of hypersensitivity, especially in patients with a history of penicillin allergy.
* Adjust dose in renal impairment.
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*This information is intended for healthcare professionals. It is essential to consult the official prescribing information and relevant clinical guidelines for complete details and to verify current recommendations before making clinical decisions.*
