Please check your internet connection and try again.
## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is an extended-spectrum penicillin 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 (cIAI)
* Complicated skin and skin-structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
* Empirical treatment of febrile neutropenia
### Adult Dosing
Standard dose: 3.375 grams (3.0g piperacillin / 0.375g tazobactam) IV every 6 hours.
High dose: 4.5 grams (4.0g piperacillin / 0.5g tazobactam) IV every 6 or 8 hours.
Maximum daily dose: Typically 18 grams (16g piperacillin / 2g tazobactam) per 24 hours for severe infections.
Dosing frequency and duration depend on the indication, severity of infection, and patient response. Specific protocols may dictate administration every 4 hours for continuous infusion or higher doses for certain indications.
### Pediatric Dosing
Dosing is based on piperacillin component.
**Patients > 2 months of age:**
* **cIAI, cSSSI, CAP, HAP, VAP:** 240 mg/kg/day piperacillin divided into 3 or 4 doses IV. Not to exceed 16 g piperacillin per day.
* **Febrile neutropenia:** 100 mg/kg/dose piperacillin every 8 hours IV. Not to exceed 4 g piperacillin per dose.
Maximum dose for neonates and infants < 2 months is not established; use with caution and close monitoring.
### Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: 2.25g or 3.375g IV every 8 hours (for standard dose regimens). For high-dose regimens, reduce dose by 25%.
* CrCl < 20 mL/min: 2.25g or 3.375g IV every 12 hours (for standard dose regimens). For high-dose regimens, reduce dose by 50%.
* Hemodialysis: 2.25g or 3.375g IV every 12 hours, plus an additional dose after each dialysis session. For high-dose regimens, reduce dose by 50%.
* **Hepatic Impairment:** No specific dose adjustment recommended, but monitor closely.
### Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated AST/ALT.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis, liver injury.
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, requiring increased monitoring of INR.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity.
### Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests (AST, ALT).
* Complete blood count (CBC) with differential, especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* Clinical response to therapy.
### Clinical Pearls
* Piperacillin/tazobactam is generally administered by IV infusion over 30 minutes.
* Continuous infusion may be considered for critically ill patients or those with severe infections to achieve higher drug concentrations and improve outcomes. Dosing for continuous infusion is typically higher (e.g., 3.375g every 8 hours as a continuous infusion or 4.5g every 8 hours).
* The reconstituted solution has limited stability; follow manufacturer guidelines for preparation and storage.
* Monitor for signs of Jarisch-Herxheimer reaction when treating syphilis.
***
*Disclaimer: This information is intended for healthcare professionals. Always consult the current official prescribing information and relevant clinical guidelines before making treatment decisions. Dosing can vary based on institutional protocols and patient-specific factors.*
