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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is bactericidal and effective against a wide range of Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
## Adult Dosing
The typical dose is 3.375 grams every 6 hours or 4.5 grams every 8 hours, administered intravenously over 30 minutes. Higher doses or more frequent administration may be required for severe infections or those caused by less susceptible organisms. Dosing frequency and total daily dose depend on the specific indication and severity of infection, as guided by institutional protocols.
## Pediatric Dosing
Dosing varies significantly by age and indication.
* **Patients 3 months and older:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight every 8 hours.
* **Nosocomial pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight every 6 hours.
* **Maximum dose:** Should not exceed the adult maximum dose.
* **Dosing is typically based on institutional protocols and patient weight.**
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 g every 6 hours or 3.375 g every 8 hours.
* CrCl < 20 mL/min: 2.25 g every 8 hours.
* Consider intermittent hemodialysis: Administer dose after dialysis.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or beta-lactamase inhibitors.
* Serious hypersensitivity reactions to other drugs containing beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, and acute kidney injury.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **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 levels. Monitor methotrexate levels.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for diarrhea, especially *C. difficile*-associated diarrhea.
* Monitor renal function, electrolytes, and liver function tests.
* Monitor complete blood count, especially in patients with prolonged therapy.
* Monitor INR in patients taking warfarin.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often used for empiric therapy of serious infections, including those involving *Pseudomonas aeruginosa* and anaerobes.
* The addition of tazobactam extends the spectrum of activity to include many beta-lactamase producing organisms.
* Dosing adjustments are crucial in patients with renal impairment.
* Bacterial resistance, particularly to *Pseudomonas aeruginosa*, can emerge during therapy; de-escalation to narrower-spectrum agents should be considered when appropriate.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for definitive dosing, administration, and safety guidance.
