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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dosing:** 3.375 g (3 g piperacillin/0.375 g tazobactam) every 6 hours IV.
* **Severe Infections/Hospital-Acquired Pneumonia:** 4.5 g (4 g piperacillin/0.5 g tazobactam) every 6 hours IV.
* **Critically Ill Patients (especially with suspected or confirmed Pseudomonas aeruginosa infection):** 4.5 g (4 g piperacillin/0.5 g tazobactam) every 4 hours IV, often as an extended or continuous infusion.
* **Maximum Daily Dose:** 18 g (16 g piperacillin/2 g tazobactam) per 24 hours.
* **Infusion Time:** Doses should be infused over at least 30 minutes. Extended or continuous infusions are often preferred for severe infections.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Patients 2 months of age and older:**
* **Mild to moderate infections:** 90 mg piperacillin/11.25 mg tazobactam per kg per dose IV every 8 hours.
* **Severe infections:** 112.5 mg piperacillin/14.1 mg tazobactam per kg per dose IV every 6 hours.
* **Maximum dose:** 4.5 g per dose.
* **Note:** Dosing recommendations for neonates and infants younger than 2 months are not well established and should be based on institutional protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 25-50% and/or increase interval to every 8 hours. For doses every 4 hours, consider reducing dose by 50% and continuing every 6 hours, or reducing dose by 33% and continuing every 6 hours. Specific recommendations vary; consult institutional guidelines.
* **Hemodialysis:** Administer 3.375 g every 8 hours. Give an additional 0.75 g dose after each dialysis session. For severe infections, consider 4.5 g every 8 hours with an additional 0.75 g dose after dialysis.
## Contraindications
* History of immediate or severe allergic reaction to piperacillin, other penicillin, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT).
* **Serious:** Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; increased INR monitoring is recommended.
* **Methotrexate:** May decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (especially in prolonged therapy for hematologic effects).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against many Gram-negative aerobes (including *Pseudomonas aeruginosa*), Gram-positive aerobes, and anaerobes.
* Extended or continuous infusions can help achieve higher and more consistent drug concentrations, particularly important for pathogens with lower susceptibility and in critically ill patients.
* The beta-lactamase inhibitor tazobactam protects piperacillin from degradation by many bacterial beta-lactamases, extending its spectrum of activity.
* Electrolyte disturbances (especially hypernatremia) can occur due to the sodium content of the drug, particularly with high doses or prolonged infusions.
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*Please verify the current prescribing information for complete details and to ensure this information aligns with local institutional protocols.*
