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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric therapy)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
High dose: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours. Dosing frequency depends on indication and severity. Duration of therapy varies by infection (e.g., 4-7 days for complicated intra-abdominal infections, minimum of 7 days for febrile neutropenia).
## Pediatric Dosing
* **Patients 3 months and older:** Dosing is based on piperacillin component.
* **2.25 grams/0.281 grams (2g piperacillin/0.25g tazobactam) per dose:** Administer every 6 hours.
* **3.0 grams/0.375 grams (3g piperacillin/0.375g tazobactam) per dose:** Administer every 6 hours.
* **4.5 grams/0.5625 grams (4g piperacillin/0.5g tazobactam) per dose:** Administer every 6 or 8 hours.
* **For febrile neutropenia:** Typically 3.0 grams/0.375 grams (3g piperacillin/0.375g tazobactam) per dose every 6 hours or 4.5 grams/0.5625 grams (4g piperacillin/0.5g tazobactam) per dose every 6-8 hours.
* Dosing may need to be adjusted for patients with renal impairment and for very low body weight infants. Consult specific pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed for standard dosing (e.g., 3.375g q6h). For higher doses or more frequent dosing, consult guidelines.
* CrCl 20-39 mL/min: 2.25g (2g piperacillin/0.25g tazobactam) IV every 6 hours.
* CrCl < 20 mL/min: 2.25g (2g piperacillin/0.25g tazobactam) IV every 8 hours.
* Hemodialysis: 2.25g (2g piperacillin/0.25g tazobactam) IV every 8 hours, plus an additional dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment recommended.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to amoxicillin or other beta-lactams.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures (especially with renal impairment or high doses), interstitial nephritis, eosinophilia, neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate serum levels. Monitor methotrexate levels.
## Monitoring
* Renal function (especially if CrCl < 40 mL/min).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Complete blood count (CBC) if prolonged therapy is anticipated.
* Liver function tests (LFTs) if clinically indicated.
## Clinical Pearls
* Administer by slow intravenous infusion over 30 minutes.
* Reconstituted solution stability varies by diluent and concentration; follow manufacturer instructions.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of activity by protecting piperacillin from degradation by many beta-lactamase enzymes.
* Consider de-escalation of therapy once culture and sensitivity results are available.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and institutional protocols before administering any medication.*
