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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic with a beta-lactamase inhibitor. Piperacillin has broad-spectrum activity against many Gram-positive, Gram-negative, and anaerobic bacteria. Tazobactam inhibits bacterial beta-lactamases, which can inactivate piperacillin.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Bacterial meningitis (in select cases based on susceptibility)
* Febrile neutropenia
## Adult Dosing
The typical dose is 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) or 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 to 8 hours. Dosing and frequency depend on the severity and type of infection and patient factors. Duration of therapy is typically 7 to 14 days. Specific dosing for febrile neutropenia is often guided by institutional protocol.
## Pediatric Dosing
Dosing is based on piperacillin weight and should be administered intravenously every 6 to 8 hours.
* **Intra-abdominal infections:** 100 mg/kg (piperacillin component) every 8 hours.
* **Hospital-acquired pneumonia:** 100 mg/kg (piperacillin component) every 8 hours or 125 mg/kg (piperacillin component) every 6 hours.
Maximum dose for pediatrics should not exceed the adult maximum of 4 grams of piperacillin per dose.
Neonates and infants < 3 months generally receive 30-50 mg/kg every 12 hours, or 30 mg/kg every 8 hours depending on gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased dosing interval is required for patients with a creatinine clearance (CrCl) < 40 mL/min.
* CrCl 20-40 mL/min: Administer 2.25 grams every 6 hours.
* CrCl < 20 mL/min: Administer 2.25 grams every 8 hours.
* Dosing should be adjusted for hemodialysis patients (typically 40 mg/kg every 8 hours, plus an additional dose after each dialysis session).
## Contraindications
* Known history of severe allergic reaction to penicillins, cephalosporins, beta-lactams, or beta-lactamase inhibitors.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and elevated liver enzymes. Serious adverse effects include anaphylaxis, Clostridioides difficile-associated diarrhea, neutropenia, thrombocytopenia, and seizures (especially with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin plasma concentrations.
* **Neuromuscular blocking agents:** May prolong the duration of neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Complete blood counts (CBC) with differential and platelet count, especially with prolonged therapy or in patients with renal impairment.
* Liver function tests (LFTs).
* Electrolytes.
## Clinical Pearls
* Administer by intravenous infusion over at least 30 minutes.
* Reconstituted solution should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Consider the spectrum of activity and local resistance patterns when initiating therapy.
* Discontinue if hypersensitivity reaction occurs.
* Monitor for electrolyte imbalances, especially in patients receiving large fluid volumes or with impaired renal function, as the drug contains sodium.
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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 relevant clinical guidelines before making treatment decisions.
