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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin, and tazobactam, a beta-lactamase inhibitor. It has bactericidal 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
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 to 8 hours. Duration of therapy is typically 7 to 14 days depending on the indication and clinical response. Dosing for complicated intra-abdominal infections and hospital-acquired pneumonia may involve higher doses or more frequent administration per local protocol.
## Pediatric Dosing
For pediatric patients aged 2 months and older:
* **Complicated intra-abdominal infections:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose given every 8 hours.
* **Hospital-acquired pneumonia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose given every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose given every 8 hours.
Maximum dose: 4.5 grams per dose. Maximum daily dose: 18 grams. Weight-based dosing for neonates and infants younger than 2 months is not established.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer the usual dose every 8 hours.
* CrCl < 20 mL/min: Administer the usual dose every 12 hours.
* Hemodialysis: Administer the usual dose every 12 hours and supplement with 0.75 grams after each dialysis session.
## Contraindications
* History of severe allergic reaction to penicillin or cephalosporins.
* Known hypersensitivity to piperacillin, tazobactam, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia.
* **Serious:** Anaphylaxis, Clostridioides difficile-associated diarrhea, seizures (especially with renal impairment or high doses), interstitial nephritis, hepatic dysfunction, hematologic changes (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, leading to increased methotrexate toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests.
* Complete blood count (especially if prolonged therapy or neutropenia is suspected).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* The combination with tazobactam broadens the spectrum of activity to include beta-lactamase producing organisms.
* Administer by slow intravenous infusion over at least 30 minutes.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Discontinue immediately if a hypersensitivity reaction occurs.
* Consider potential for cross-reactivity in patients with penicillin allergy.
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*This information is intended for clinical pharmacy professionals and does not replace the official prescribing information. Always verify current prescribing information and local protocols before making therapeutic decisions.*
