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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. This combination broadens the spectrum of activity of piperacillin to include many beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
The usual dose is 3.375 g (piperacillin 3 g/tazobactam 0.375 g) every 6 hours, or 4.5 g (piperacillin 4 g/tazobactam 0.5 g) every 6 or 8 hours, administered intravenously.
Dosing varies based on indication and severity of infection. Higher doses (e.g., 4.5 g every 6 hours) may be used for severe infections or those caused by less susceptible organisms. Duration of therapy is typically 7 to 14 days.
## Pediatric Dosing
* **For patients 2 months and older:**
* Dosing is based on the piperacillin component.
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight every 8 hours.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight every 8 hours OR 75 mg piperacillin/9.375 mg tazobactam per kg of body weight every 6 hours.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight every 8 hours.
* Maximum dose: 4.5 g per dose.
* For patients weighing over 40 kg, use adult doses.
* **Neonates and infants younger than 2 months:** Dosing is not established due to immature renal and hepatic function.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* Doses should be reduced and/or dosing intervals extended.
* For 3.375 g every 6 hours regimen:
* CrCl 20-40 mL/min: 2.25 g every 6 hours.
* CrCl < 20 mL/min: 2.25 g every 8 hours.
* For 4.5 g every 8 hours regimen:
* CrCl 20-40 mL/min: 3.375 g every 8 hours.
* CrCl < 20 mL/min: 2.25 g every 8 hours.
* For 4.5 g every 6 hours regimen:
* CrCl 20-40 mL/min: 3.375 g every 6 hours.
* CrCl < 20 mL/min: 2.25 g every 6 hours.
* Hemodialysis: Administer dose at the end of dialysis and extend interval.
## Contraindications
* Known history of severe allergic reaction to piperacillin, other penicillins, other beta-lactam antibiotics, or tazobactam.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, increased liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, hemolytic anemia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the efficacy of warfarin, monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Complete blood count (CBC) for potential hematologic effects.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Piperacillin/tazobactam is associated with a higher risk of hypersensitivity reactions compared to other penicillins.
* Ensure adequate hydration to minimize the risk of crystalluria.
* For suspected or confirmed carbapenem-resistant Enterobacteriaceae (CRE) or *Pseudomonas aeruginosa* infections, consider alternative agents or combination therapy.
* Tazobactam alone does not provide significant antibacterial activity.
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*This information is intended for clinical use and does not replace professional judgment. Always consult the current prescribing information and relevant guidelines before making treatment decisions.*
