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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor.
## 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 adult dose is 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) every 6 hours intravenously.
Higher doses of 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) every 6 hours intravenously are used for more severe infections or hospital-acquired pneumonia.
Maximum daily dose should not exceed 18 grams (piperacillin 16 grams / tazobactam 2 grams).
## Pediatric Dosing
Dosing is based on piperacillin content.
* **Patients 2 months and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin / 1.25 mg tazobactam per kg administered every 8 hours intravenously.
* **Hospital-acquired pneumonia:** 100 mg piperacillin / 1.25 mg tazobactam per kg administered every 8 hours intravenously.
* **Febrile neutropenia:** 100 mg piperacillin / 1.25 mg tazobactam per kg administered every 6 hours intravenously.
* **Maximum dose:** 18 grams per day (piperacillin 16 grams / tazobactam 2 grams).
## Dose Adjustments
* **Renal Impairment:**
* If CrCl is > 20 mL/min, no dose adjustment is needed.
* If CrCl is 20-40 mL/min, administer the usual dose every 8 hours.
* If CrCl is < 20 mL/min, administer the usual dose every 12 hours.
* Hemodialysis: Administer dose every 12 hours and give an additional 2.25g dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam therapy.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, pruritus, elevated liver enzymes.
Serious: Anaphylaxis, Clostridioides difficile-associated diarrhea, seizures, interstitial nephritis, hepatotoxicity.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels; monitor methotrexate levels and consider dose adjustments.
## Monitoring
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of Clostridioides difficile infection.
* Renal function (especially with concomitant nephrotoxic agents).
* Liver function tests.
* Hematologic parameters.
* INR if patient is on warfarin.
* Methotrexate levels if patient is on methotrexate.
## Clinical Pearls
* Bactericidal activity is reduced in the presence of beta-lactamase-producing organisms.
* The duration of treatment depends on the severity and type of infection.
* Prepare reconstituted solutions according to manufacturer instructions and infuse over at least 30 minutes to minimize infusion-related reactions.
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*Disclaimer: This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive patient management.*
