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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
* **Severe Infections/Hospital-Acquired Pneumonia:** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
* **Continuous Infusion (for severe infections or critical illness):** 13.5 grams (12g piperacillin/1.5g tazobactam) per 24 hours as a continuous infusion. Dosing may vary by institution.
* **Maximum Daily Dose:** Generally not to exceed 13.5 grams per day.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Patients 0 to 12 months:** Dosing varies significantly by indication and weight. Consult specific pediatric guidelines.
* **Patients 1 to 12 years:**
* **Complicated Intra-abdominal Infections:** 90 to 100 mg piperacillin/11.25 to 12.5 mg tazobactam per kg per dose intravenously every 6 hours or 80 to 90 mg piperacillin/10 to 11.25 mg tazobactam per kg per dose every 8 hours.
* **Febrile Neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 6 hours.
* **Maximum Dose:** Generally not to exceed 4.5 grams per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* For intermittent infusions (e.g., 3.375g or 4.5g every 6 or 8 hours), reduce frequency to every 8 or 12 hours.
* For continuous infusion (e.g., 13.5g/24hr), reduce the infusion rate by 50%.
* Dose should be adjusted further based on the degree of renal impairment and clinical response.
* **Hemodialysis:** Administer dose after dialysis and adjust frequency every 8 hours. An additional dose of 2.25 grams (2g piperacillin/0.25g tazobactam) should be administered after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, phlebitis.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, neutropenia, thrombocytopenia, increased serum creatinine and BUN, hepatic dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (LFTs)
* Complete blood count (CBC) with differential and platelet count
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea
## Clinical Pearls
* For intermittent infusion, reconstitute powder with sterile water for injection and dilute further in a compatible IV fluid (e.g., 0.9% sodium chloride, 5% dextrose).
* For continuous infusion, reconstitution and dilution require specific protocols. Refer to manufacturer's instructions or institutional guidelines.
* Piperacillin/tazobactam is typically reconstituted and infused over 30 minutes (intermittent) or as a continuous infusion.
* Extended infusion (over 4 hours) may be considered for some critically ill patients to optimize pharmacokinetic/pharmacodynamic targets.
* The risk of hypersensitivity reactions is higher in patients with a history of penicillin allergy.
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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 protocols before administering any medication.
