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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. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
Higher dose: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours, or 3.375 grams IV every 4 hours for severe infections or those caused by less susceptible organisms.
Maximum dose: Generally, 4.5 grams IV every 4 hours or 18 grams per day.
## Pediatric Dosing
Dosing in pediatric patients is highly variable and depends on indication, patient weight, and severity of illness. A common approach for serious infections is:
* Neonates and infants: 80 mg piperacillin/10 mg tazobactam per kg per dose IV every 8 to 12 hours.
* Children 3 months to 12 years: 90 to 100 mg piperacillin/11.25 to 12.5 mg tazobactam per kg per dose IV every 6 to 8 hours.
Maximum pediatric dose is typically capped at the adult maximum per dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) IV every 6 hours or 3.375 grams IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours.
* For patients on intermittent hemodialysis, give 2.25 grams IV every 8 hours, and administer an additional 0.75 grams dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to any beta-lactam antibacterial.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, pruritus, fever, elevated liver enzymes (AST, ALT).
Serious: Anaphylaxis, Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis.
## 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 efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and during therapy).
* Liver function tests (baseline and periodically).
* Complete blood count (periodic monitoring, especially with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* Piperacillin/tazobactam is often used for broad-spectrum empiric therapy, especially in critically ill patients or those with suspected resistant organisms.
* Reconstitution and further dilution are required for intravenous administration. Infusion rates should be slow to minimize adverse effects.
* When reconstituting, use sterile water for injection or compatible IV fluids. Further dilute in a compatible IV fluid such as 0.9% sodium chloride or 5% dextrose to a concentration no greater than 40 mg piperacillin/5 mg tazobactam per mL.
* The infusion time for doses of 2.25 g/0.281 g or 3.375 g/0.422 g should be no less than 30 minutes. The infusion time for doses of 4.5 g/0.563 g should be no less than 40 minutes.
* Avoid co-administration with other antibiotics in the same IV line if incompatibilities exist.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and local protocols for definitive guidance.
