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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 bactericidal and effective 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
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia
## Adult Dosing
Common adult doses are 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) administered intravenously every 6 or 8 hours. The choice of dose and frequency depends on the severity and type of infection, and local institutional guidelines. The maximum recommended daily dose of piperacillin is typically 18 grams.
## Pediatric Dosing
For pediatric patients (ages 2 months and older):
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose, administered intravenously every 8 hours.
* **Hospital-acquired pneumonia:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose, administered intravenously every 6 hours.
Dosing should not exceed the maximum adult dose. Dosing for neonates and infants younger than 2 months is not well established.
## Dose Adjustments
* **Renal Impairment:** Reduce dose and/or extend interval based on creatinine clearance (CrCl).
* CrCl 50-80 mL/min: Administer every 8 hours.
* CrCl 20-50 mL/min: Administer every 12 hours.
* CrCl < 20 mL/min: Administer every 24 hours.
* For patients on hemodialysis, administer dose every 12 hours and supplement with an additional dose after each hemodialysis session.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
* History of immediate and severe allergic reaction to penicillin or cephalosporins.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and elevated liver enzymes. Serious adverse effects can include *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures, neutropenia, and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin and tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin, requiring increased monitoring of INR.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, potentially leading to toxicity.
* **Aminoglycosides:** While often used synergistically, co-administration requires separate administration due to potential physical inactivation.
## Monitoring
* Renal function (creatinine, CrCl) for dose adjustments.
* Liver function tests.
* Complete blood count (CBC), especially in prolonged therapy, for potential hematologic effects.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
## Clinical Pearls
* Reconstituted solutions should be used within a specified time frame (e.g., 24 hours at room temperature or 48 hours refrigerated, depending on diluent).
* Dosing frequency for adults is often every 6 hours for severe infections and every 8 hours for less severe infections, though this can vary by local protocol.
* Tazobactam protects piperacillin from degradation by many beta-lactamases, broadening its spectrum of activity.
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*This information is for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any clinical decisions.*
