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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibacterial and beta-lactamase inhibitor.
## 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 is 3.375 g intravenously every 6 hours or 4.5 g intravenously every 8 hours. Dosing is based on piperacillin content (e.g., 3 g piperacillin/0.375 g tazobactam or 4 g piperacillin/0.5 g tazobactam). Duration of therapy varies by indication and clinical response, typically 7-14 days.
## Pediatric Dosing
* **3 months to < 12 years of age:** 90-100 mg piperacillin component per kg per dose intravenously every 8 hours. For cystic fibrosis patients, 100 mg piperacillin component per kg per dose every 6 hours. Maximum dose is typically 100 mg piperacillin component/kg/dose, not to exceed the adult dose of 4.5 g per dose.
* **12 years of age and older:** Same as adult dosing.
## Dose Adjustments
* **Renal Impairment:** Adjust dose based on creatinine clearance (CrCl).
* CrCl 20-50 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* Hemodialysis: Administer usual dose every 12 hours and supplement with an additional dose equal to one-third of the usual dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment recommended.
## Contraindications
* Known serious allergy to piperacillin, tazobactam, or other beta-lactam antibiotics.
* History of hypersensitivity to piperacillin-tazobactam.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, eosinophilia, elevated liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with renal impairment and high doses), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin-tazobactam.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; increased monitoring of INR is recommended.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests.
* Complete blood count (CBC) for hematologic changes.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Piperacillin-tazobactam has broad-spectrum activity, including against many Gram-negative organisms (including *Pseudomonas aeruginosa*), Gram-positive organisms, and anaerobes.
* Dose adjustments for renal impairment are crucial.
* The beta-lactamase inhibitor tazobactam extends the spectrum of activity of piperacillin against beta-lactamase-producing bacteria.
* Preparation and administration require careful attention to product labeling, as formulations and reconstitution instructions may vary.
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*Disclaimer: This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols for definitive guidance.*
