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# Piperacillin/Tazobactam (Zosyn)
## 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, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (in combination with an antipseudomonal agent, if indicated)
## Adult Dosing
* **Standard Dosing:** 3.375 g (3 g piperacillin/0.375 g tazobactam) intravenously every 6 hours.
* **Severe Infections/Pseudomonas Coverage:** 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 or 8 hours. Higher doses (e.g., 3.375 g every 4 hours) may be used for severe infections or critically ill patients, but specific dosing often depends on institutional protocols.
* **Maximum Dose:** Not explicitly defined but typically capped by the frequency and infusion duration.
## Pediatric Dosing
Dosing is based on piperacillin component and patient weight. Actual dosing often depends on institutional protocols.
* **Patients 2 months and older:**
* **Complicated Intra-abdominal Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Complicated Skin and Skin Structure Infections:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose intravenously every 6 hours.
* **Nosocomial Pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Maximum Dose:** Generally not to exceed the adult dose of 4.5 g per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce frequency. For standard 6-hour dosing, administer every 8 hours. For 8-hour dosing, administer every 12 hours. Consider a 50% dose reduction for CrCl < 20 mL/min.
* **Hemodialysis:** Administer a dose after each dialysis session. Dose reduction may be necessary.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, abdominal pain.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes, renal dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect; increased INR monitoring is advised.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; increased toxicity may occur.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** With prolonged therapy, monitor for hematologic changes.
* **Signs and symptoms of hypersensitivity reactions.**
* **Signs and symptoms of *C. difficile*-associated diarrhea.**
## Clinical Pearls
* Infuse intravenously over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* Piperacillin/tazobactam is a broad-spectrum agent and should be used judiciously to minimize the development of resistance.
* Gram stain and culture and sensitivity testing should be performed before initiating treatment when clinically indicated.
* Dose and frequency for severe infections or critically ill patients should be guided by clinical response, renal function, and local institutional protocols.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for complete and up-to-date information before making any treatment decisions.*
