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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 has a broad spectrum of activity against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia (hospital-acquired pneumonia and ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
* Complicated urinary tract infections, including pyelonephritis
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
Higher dose for severe infections or *Pseudomonas* coverage: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours.
* **Maximum dose:** Typically 4.5 grams every 6 hours. Specific maximums may depend on indication and institutional guidelines.
* **Duration:** Varies based on infection severity and response, generally 7-14 days.
## Pediatric Dosing
Dosing varies significantly by age and indication. Consult specific pediatric guidelines.
* **General guideline (over 12 years):** 3.375 grams IV every 6 hours.
* **General guideline (2 months to 12 years):** Dosing is typically calculated based on piperacillin weight-based dose, ranging from 25 mg/kg to 100 mg/kg per dose (using the piperacillin component) IV every 6 or 8 hours. The tazobactam component is dosed proportionally.
* **Neonates:** Dosing is complex and requires expert consultation.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: 2.25 grams IV every 6 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours.
* For doses of 4.5 grams every 6 hours, adjust by administering 3.375 grams IV every 6 hours when CrCl is 20-39 mL/min, and 3.375 grams IV every 8 hours when CrCl is < 20 mL/min.
* Hemodialysis: Administer 2.25 grams IV every 8 hours, plus 0.75 grams IV after each dialysis session.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics.
* History of immediate or severe allergic reaction to penicillin or cephalosporins.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), Stevens-Johnson syndrome/toxic epidermal necrolysis, interstitial nephritis, hematologic changes (neutropenia, thrombocytopenia, eosinophilia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** While sometimes co-administered, there is a potential for inactivation of piperacillin in the presence of aminoglycosides in vitro. Avoid co-administration in the same IV bag.
## Monitoring
* Renal function (creatinine, BUN)
* Liver function tests
* Complete blood count (including platelets)
* Signs and symptoms of infection (fever, WBC count, inflammatory markers)
* Electrolytes
* Signs of hypersensitivity reactions
* Stool for *C. difficile* if diarrhea develops
## Clinical Pearls
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours if refrigerated. Consult manufacturer labeling for specific stability data.
* Administration is typically via IV infusion over 30 minutes.
* May be used for empiric therapy in critically ill patients due to broad spectrum.
* Discontinue immediately if hypersensitivity reaction occurs.
* Adjust dose for renal impairment.
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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 relevant clinical guidelines for complete details before making treatment decisions.*
