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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic and 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 (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
Standard adult dosing is typically **3.375 grams (piperacillin 3 g / tazobactam 0.375 g) or 4.5 grams (piperacillin 4 g / tazobactam 0.5 g)** given intravenously every 6 to 8 hours. Dosing frequency and duration depend on the indication, severity of infection, and clinical response. Higher doses and more frequent administration may be used for severe infections. The maximum daily dose for adults is generally **18 grams (piperacillin 16 g / tazobactam 2 g)**.
## Pediatric Dosing
* **For children 2 months to 12 years of age:** Dosing is based on piperacillin weight.
* **Uncomplicated intra-abdominal infections:** 90 mg piperacillin / 11.25 mg tazobactam per kg per dose, administered every 8 hours.
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, or community-acquired pneumonia:** 112.5 mg piperacillin / 14.1 mg tazobactam per kg per dose, administered every 6 hours.
* Maximum dose: 4.5 grams per dose.
* **Children < 2 months of age:** Dosing recommendations are not well established and should be guided by clinical judgment and institutional protocols.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased dosing interval is required for CrCl < 20 mL/min.
* For a 6-hour interval: 2.25 g IV every 8 hours.
* For an 8-hour interval: 2.25 g IV every 12 hours.
* For CrCl 20-50 mL/min, increase the dosing interval. Consult prescribing information for specific recommendations.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin-class drugs, or any component of the formulation.
* History of immediate and severe allergic reaction to penicillin or beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, increased liver enzymes, elevated creatinine.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, prolonged prothrombin time.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** Piperacillin may decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, BUN)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC) with differential, especially if prolonged therapy
* Electrolytes
* Signs and symptoms of infection (fever, WBC count, clinical improvement)
* Signs of hypersensitivity reactions
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum antibiotic, but resistance can occur. Consider de-escalation once culture and sensitivity results are available.
* Adjust dose for renal impairment.
* Monitor for diarrhea and consider *C. difficile* infection.
* Administer infused over at least 30 minutes to reduce the risk of infusion-related reactions.
* Ensure adequate hydration to minimize the risk of crystalluria.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines before making any treatment decisions.
