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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination beta-lactam/beta-lactamase inhibitor antibiotic. Piperacillin is a broad-spectrum penicillin antibiotic, and tazobactam is a beta-lactamase inhibitor that 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
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (as part of combination therapy)
## Adult Dosing
Standard adult dose is **3.375 grams** (3g piperacillin / 0.375g tazobactam) or **4.5 grams** (4g piperacillin / 0.5g tazobactam) administered intravenously every 6 or 8 hours.
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia:** Typically **4.5 grams IV every 6 hours**. Duration varies based on infection severity and clinical response, generally 7-14 days.
* **Hospital-acquired pneumonia:** Typically **4.5 grams IV every 6 hours**. Duration generally 7 days.
* **Febrile neutropenia:** Typically **4.5 grams IV every 6 hours**, often used in combination with an aminoglycoside. Duration generally 7 days or until resolution of neutropenia and fever.
* **Maximum dose:** Not explicitly defined, but doses higher than 4.5 grams IV every 6 hours are uncommon.
## Pediatric Dosing
Dosing is based on the piperacillin component.
* **Children < 12 years:** Dosing varies based on indication and local protocol. Common regimens include **90 mg/kg/dose (80 mg piperacillin/10 mg tazobactam) IV every 6 hours** or **112.5 mg/kg/dose (100 mg piperacillin/12.5 mg tazobactam) IV every 8 hours**. Maximum single dose should not exceed the adult dose of 4.5 grams.
* **Children ≥ 12 years:** Dosed as adults, typically **4.5 grams IV every 6 hours**.
* **Neonates and infants < 2 months:** Generally not recommended due to immature renal and hepatic function. Dosing, if necessary, requires careful consideration of weight, gestational and postnatal age, and renal function, and is often guided by specialist recommendations.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased interval is required for creatinine clearance (CrCl) < 40 mL/min.
* CrCl 20-40 mL/min: **2.25 grams IV every 6 hours** or **3.375 grams IV every 8 hours**.
* CrCl < 20 mL/min: **2.25 grams IV every 8 hours**.
* Hemodialysis: Administer **2.25 grams IV every 8 hours** plus an additional **1.125 grams** after each dialysis session.
* **Hepatic Impairment:** No dose adjustment necessary.
## Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam therapy.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain, elevated liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, leukopenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; increased monitoring of INR is recommended.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Bacteriostatic agents (e.g., tetracyclines, chloramphenicol):** May antagonize the action of piperacillin.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for diarrhea and assess for *C. difficile*.
* Monitor renal function (BUN, creatinine) and electrolytes, especially in patients with renal impairment or those receiving nephrotoxic agents.
* Monitor liver function tests (AST, ALT, bilirubin).
* Monitor complete blood count (CBC) for potential hematologic changes, particularly with prolonged therapy.
* Monitor for signs of superinfection.
## Clinical Pearls
* Administer infusion over at least 30 minutes to reduce the risk of infusion-related reactions.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours if refrigerated.
* Adequate fluid intake is important for patients with renal impairment.
* Discontinue if hypersensitivity reaction occurs.
* The efficacy of piperacillin-tazobactam in treating infections caused by piperacillin-resistant Gram-negative organisms is not established.
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***Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines for definitive patient management decisions.*
