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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and a beta-lactamase inhibitor. It has broad-spectrum activity against many gram-positive, gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) IV every 6 hours.
* **Higher Dose (for severe infections or specific pathogens):** 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) IV every 6 hours or every 8 hours.
* **Duration:** Typically 7 to 14 days, depending on the infection.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Patients 3 months and older:** 100 mg/kg (piperacillin component) IV every 8 hours. For serious infections, 125 mg/kg (piperacillin component) IV every 6 hours.
* **Maximum dose:** Do not exceed the adult maximum of 4 grams of piperacillin per dose.
* **Note:** Tazobactam is dosed at 1/8th the weight-based dose of piperacillin.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: 2.25 g (piperacillin 2g/tazobactam 0.25g) IV every 6 hours or 3.375 g (piperacillin 3g/tazobactam 0.375g) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g (piperacillin 2g/tazobactam 0.25g) IV every 8 hours.
* **Hemodialysis:** Give a dose after each dialysis session.
* **Hepatic Impairment:** No specific guidelines, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin derivatives, or cephalosporins.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, liver enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Warfarin:** May decrease the effect of warfarin; increased monitoring of INR is recommended.
* **Neuromuscular blocking agents:** May prolong the neuromuscular blockade.
* **Methotrexate:** May decrease methotrexate levels.
## Monitoring
* Monitor for signs of hypersensitivity reactions.
* Monitor for signs and symptoms of *C. difficile* infection.
* Monitor renal and hepatic function.
* Monitor complete blood counts, especially with prolonged therapy.
* Monitor electrolytes.
## Clinical Pearls
* Piperacillin/tazobactam is often reconstituted and further diluted for IV infusion over 30 minutes.
* The 3.375 g and 4.5 g formulations contain different ratios of piperacillin to tazobactam (8:1 and 8:1, respectively). Ensure correct product is used for dosing.
* Consider de-escalation of therapy once culture and sensitivity results are available.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most up-to-date and complete information before making any treatment decisions.*
