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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. This combination extends the spectrum of activity of piperacillin to include many beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
Standard dose: 3.375 grams (piperacillin 3g/tazobactam 0.375g) intravenously every 6 hours.
Higher doses for severe infections or certain pathogens: 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 6 or 8 hours.
Maximum daily dose: 18 grams (piperacillin 16g/tazobactam 2g) intravenously.
Duration of therapy depends on indication and clinical response, typically 7-14 days.
## Pediatric Dosing
Dosing varies by indication and age/weight.
**Children 2 months and older:**
* **Complicated Intra-abdominal Infections:** 100 mg piperacillin component/kg/day divided into 4 doses (e.g., 25 mg piperacillin component/kg every 6 hours). Maximum 4.5 grams per dose.
* **Hospital-acquired pneumonia:** 100 mg piperacillin component/kg/day divided into 4 doses (e.g., 25 mg piperacillin component/kg every 6 hours). Maximum 4.5 grams per dose.
* **Febrile Neutropenia:** 300 mg piperacillin component/kg/day divided into 4 doses (e.g., 75 mg piperacillin component/kg every 6 hours). Maximum 4.5 grams per dose.
*Note: Tazobactam component is typically dosed at 1/8th of the piperacillin component.*
*Refer to specific pediatric guidelines or institutional protocols for precise dosing based on indication and renal function.*
## Dose Adjustments
**Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 hours.
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours.
* Hemodialysis: Give a 4.5g dose every 12 hours and administer an additional 1.125g dose after each dialysis session.
**Hepatic Impairment:** No specific dose adjustments are recommended, but caution is advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, acute kidney injury.
## 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, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Complete blood count (including platelets and neutrophils), especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile* infection.
* Clinical signs of infection (temperature, white blood cell count, culture results).
## Clinical Pearls
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Rapid infusion can lead to hypersensitivity reactions. Administer intravenously over at least 30 minutes.
* Due to its sodium content, caution is advised in patients on sodium restriction.
* The 3.375g formulation contains 2.35 mmol sodium per gram of piperacillin. The 4.5g formulation contains 2.43 mmol sodium per gram of piperacillin.
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*Disclaimer: This information is intended for clinical pharmacists and healthcare professionals. It is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols before administering any medication.*
