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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
* 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 6 or 8 hours.
* **Maximum Dose:** Typically based on the piperacillin component; doses exceeding 4.5 grams every 6 hours are rarely used and require specific justification. Duration of therapy is variable, often 7-14 days depending on indication and clinical response.
## Pediatric Dosing
Dosing varies significantly by indication and age/weight. A common regimen for serious infections in patients **≥ 12 years**: 3.375 grams IV every 6 hours. For **children < 12 years**: Dosing is often calculated based on piperacillin content, typically ranging from 80-100 mg piperacillin/10 mg tazobactam per kg per dose administered every 6 or 8 hours. Dosing for neonates and infants requires careful consideration due to immature renal function and is often weight-based, given every 8 or 12 hours. **Consult specific pediatric guidelines or formulary for precise dosing.**
## Dose Adjustments
* **Renal Impairment:**
* CrCl 20-50 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* Hemodialysis: Administer usual dose every 8 hours, with an additional dose of 1.125 grams after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known history of severe allergic reaction (e.g., anaphylaxis) to piperacillin, tazobactam, other beta-lactam antibiotics, or penicillin.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, renal failure, liver injury.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Neuromuscular blocking agents:** May prolong the duration of neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Aminoglycosides:** While often used concomitantly, avoid co-administration in the same IV line due to potential inactivation.
## Monitoring
* Renal function (BUN, creatinine).
* Liver function tests (AST, ALT).
* Complete blood count (CBC), particularly for prolonged therapy or suspicion of hematologic effects.
* Signs and symptoms of infection and response to treatment.
* Signs and symptoms of hypersensitivity reactions and *C. difficile* infection.
## Clinical Pearls
* Piperacillin-tazobactam has a broad spectrum, including *Pseudomonas aeruginosa* and many anaerobes.
* Reconstitution and further dilution are required for IV infusion. Infusion rate should be slow (over at least 30 minutes) to reduce the risk of infusion-related reactions.
* Monitor for signs of superinfection, especially with prolonged use.
* Discontinue if a hypersensitivity reaction occurs.
* In patients with cystic fibrosis, higher doses may be required.
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*This information is intended for clinical decision support and does not replace a thorough review of the current prescribing information and institutional protocols.*
