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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial agent and a beta-lactamase inhibitor. It has a broad spectrum of activity against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **High Dose (for severe infections, especially hospital-acquired pneumonia or documented resistant organisms):** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 hours.
* **Maximum Dose:** Not explicitly defined, but higher doses are used for severe infections.
## Pediatric Dosing
* **Children < 2 months:** Dosing is not established and generally not recommended due to safety concerns.
* **Children ≥ 2 months:**
* **General:** 90 mg piperacillin/11.25 mg tazobactam per kg per dose intravenously every 8 hours.
* **Severe Infections (e.g., febrile neutropenia, hospital-acquired pneumonia):** 120 mg piperacillin/15 mg tazobactam per kg per dose intravenously every 8 hours.
* **Maximum Dose:** Typically capped at the adult dose of 4.5 grams per dose. Dosing for children > 50 kg should not exceed the adult dose.
* *Note: Specific pediatric dosing protocols may vary; consult institutional guidelines.*
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce frequency to every 8 hours (standard dose) or every 12 hours (high dose). For CrCl < 20 mL/min, consider giving 2.25 g (2g/0.25g) every 8 hours or 3.375 g (3g/0.375g) every 8 hours for standard and high dose respectively. Adjustments are also needed for CrCl 20-40 mL/min.
* **Hepatic Impairment:** No dose adjustment recommended.
* **Hemodialysis:** Administer dose after hemodialysis and supplement with 1.125 g (1g/0.125g) or 2.25 g (2g/0.25g) dose.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillin antimicrobials, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizure, neutropenia, thrombocytopenia, leukopenia, eosinophilia, prolonged prothrombin time.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate serum levels. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (especially in prolonged therapy).
* Electrolytes.
* Prothrombin time/INR, especially if co-administered with anticoagulants.
* Signs and symptoms of hypersensitivity or *C. difficile* infection.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many beta-lactamases, extending its spectrum of activity.
* Dosing is based on the piperacillin component.
* Ensure adequate hydration in patients with impaired renal function.
* Discontinue if hypersensitivity reaction occurs.
* Use with caution in patients with a history of gastrointestinal disease, particularly colitis.
* The 3.375 g and 4.5 g formulations are **not** interchangeable on a weight-for-weight basis due to different piperacillin:tazobactam ratios.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols for definitive guidance. Dosing and recommendations may vary.*
