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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of a broad-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). Tazobactam protects piperacillin from degradation by many bacterial beta-lactamases, thereby extending its spectrum of activity.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Usual dose:** 3.375 grams (piperacillin 3g/tazobactam 0.375g) intravenously every 6 hours.
* **Severe infections/higher inoculums:** 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 6 or 8 hours.
* **Maximum dose:** Generally not to exceed 18 grams (piperacillin 16g/tazobactam 2g) per day divided into 3 or 4 doses. Specific dosing for febrile neutropenia may vary based on institutional 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 intravenously every 8 hours.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg intravenously every 8 hours, OR 75 mg piperacillin/9.375 mg tazobactam per kg intravenously every 6 hours.
* **Maximum pediatric dose:** Doses should not exceed the maximum adult dose of 4.5 grams per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce frequency to every 8 hours. If on hemodialysis, administer dose every 8 hours and supplement with an additional dose after each hemodialysis session.
* **Hepatic Impairment:** No dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate and severe allergic reaction to amoxicillin or amoxicillin/clavulanate.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, leukopenia), liver enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Methotrexate:** Piperacillin may decrease methotrexate serum concentrations.
* **Warfarin:** Monitor INR closely as piperacillin-tazobactam may decrease warfarin's anticoagulant effect.
## Monitoring
* Renal function (BUN, creatinine).
* Liver function tests (AST, ALT, bilirubin).
* Complete blood count (CBC) with differential, especially for prolonged treatment.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
## Clinical Pearls
* Piperacillin-tazobactam is a significant contributor to antibiotic-associated diarrhea and *C. difficile* infection.
* Reconstituted solution is typically stable for 24 hours at room temperature or 48 hours under refrigeration. Further dilution for IV infusion is also stable for 24 hours at room temperature or 48 hours refrigerated.
* The extended-release formulation (if available) has different dosing recommendations.
* Dosing for specific indications like febrile neutropenia may be guided by institutional protocols.
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*Disclaimer: This information is intended for healthcare professionals. Always verify current prescribing information, guidelines, and institutional protocols before making clinical decisions.*
