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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. Piperacillin targets bacterial cell wall synthesis, while tazobactam protects piperacillin from degradation by beta-lactamase enzymes produced by susceptible 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 is 3.375 g (3 g piperacillin/0.375 g tazobactam) or 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 hours. Duration varies by indication and patient response, typically 7-14 days. Dosing for febrile neutropenia may differ based on local protocols.
## Pediatric Dosing
* **Patients 2 months and older:** Dosing is based on piperacillin component.
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours. Maximum dose: 3.375 g per dose.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours OR 75 mg piperacillin/9.375 mg tazobactam per kg per dose IV every 6 hours. Maximum dose: 3.375 g per dose.
* Dosing for febrile neutropenia in pediatric patients should follow established institutional guidelines.
* Neonates and infants younger than 2 months: Safety and efficacy not established.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer same dose every 8 hours.
* CrCl < 20 mL/min: Administer same dose every 12 hours.
* Hemodialysis: Administer dose every 12 hours and supplement with 0.75 g after each dialysis session.
* Hepatic impairment: No dose adjustment generally required.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, pain at injection site.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome, DRESS), seizures (especially with high doses or renal impairment), hematologic abnormalities (neutropenia, thrombocytopenia), liver enzyme elevations, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin, potentially increasing INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function
* Liver function tests
* Complete blood count (especially if prolonged therapy or suspected hematologic effects)
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile*-associated diarrhea
* Electrolytes
* INR if patient is on warfarin
## Clinical Pearls
* Administer intravenously over at least 30 minutes.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated.
* Risk of cross-reactivity in patients with penicillin allergy. Use with caution.
* Tazobactam alone has minimal antibacterial activity but broadens piperacillin's spectrum.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before making clinical decisions.*
