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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including many beta-lactamase producing strains.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
Doses are expressed as piperacillin-tazobactam. Each 3.375 g vial contains 3 g piperacillin and 0.375 g tazobactam. Each 4.5 g vial contains 4 g piperacillin and 0.5 g tazobactam.
Duration of therapy is typically 7-14 days, depending on severity and clinical response.
## Pediatric Dosing
* **3 months to < 12 years:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* Maximum dose: 4.5 grams/0.5625 grams per dose.
* **12 years and older:** Dosing as per adult recommendations.
* Dosing in neonates and infants < 3 months is not established and requires careful consideration due to immature renal function.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: 2.25 grams IV every 6 hours or 3.375 grams IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours or 3.375 grams IV every 12 hours.
* Consider intermittent hemodialysis: Dose after dialysis.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known serious allergic reaction to penicillins, cephalosporins, beta-lactams, or piperacillin-tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation.
* **Serious:**
* Hypersensitivity reactions (anaphylaxis, angioedema)
* Clostridioides difficile-associated diarrhea
* Seizures (especially with high doses or renal impairment)
* Hepatotoxicity
* Hematologic changes (neutropenia, thrombocytopenia, anemia)
* Acute kidney injury
## 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 INR; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and during therapy)
* Liver function tests (baseline and during therapy)
* Complete blood count (baseline and during therapy, especially for prolonged treatment)
* Signs and symptoms of infection
* Electrolytes
* Signs of hypersensitivity reactions
* Monitor for signs of C. difficile infection.
## Clinical Pearls
* Piperacillin-tazobactam has a broad spectrum of activity but resistance is increasing. Consider local antibiograms.
* Administer IV infusion over at least 30 minutes to reduce the risk of infusion-related reactions.
* Reconstituted solution stability varies; follow manufacturer's instructions.
* Dosing for febrile neutropenia may differ based on institutional protocols, often involving higher doses and longer durations.
* The risk of seizures may be increased in patients with renal impairment.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and institutional guidelines for complete and up-to-date details.*
