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# Piperacillin-tazobactam (Zosyn)
## Overview
A fixed-ratio combination of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It provides bactericidal activity against many Gram-positive, Gram-negative, and anaerobic organisms.
## Primary Indications
* Moderate-to-severe infections: hospital-acquired pneumonia, intra-abdominal infections, skin and skin structure infections, and sepsis.
* Empiric coverage for febrile neutropenia.
## Adult Dosing
* **Standard:** 3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 6 hours.
* **Severe Infections (e.g., Pseudomonas pneumonia):** 4.5 g (4 g piperacillin / 0.5 g tazobactam) IV every 6 hours.
* **Extended Infusion:** 4.5 g infused over 4 hours every 8 hours is often utilized to optimize pharmacodynamics (time above MIC).
* **Maximum Dose:** 18 g (piperacillin component) per day.
## Pediatric Dosing
* **Neonates (≤ 9 months):** Dosage varies significantly by weight and age—consult institutional guidelines.
* **Pediatrics (≥ 9 months):** 100 mg/kg (piperacillin component) every 8 hours for intra-abdominal infections.
* **NOTE:** Always use institutional weight-based protocols; dosing varies by infection severity.
## Dose Adjustments
* **Renal Impairment:** Requires reduction based on creatinine clearance (CrCl).
* CrCl 20–40 mL/min: Reduce dose to 2.25 g every 6 hours or 3.375 g every 8 hours.
* CrCl < 20 mL/min: Reduce dose to 2.25 g every 8 hours.
* **Hemodialysis:** Significant removal; 2.25 g after each dialysis session is common.
## Contraindications
* History of severe hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome) to piperacillin, tazobactam, or any beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, headache, constipation, nausea, insomnia.
* **Serious:** C. difficile-associated diarrhea, hypersensitivity reactions, seizures (rare, mostly in setting of renal failure), and hematologic toxicity (thrombocytopenia/leukopenia with prolonged therapy > 14 days).
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides physically; administer at least 1 hour apart.
* **Probenecid:** Increases serum concentrations of piperacillin/tazobactam.
* **Warfarin:** Beta-lactams may alter gut flora and vitamin K synthesis, potentially increasing INR.
* **Methotrexate:** Penicillins may decrease renal clearance, increasing risk of toxicity.
## Monitoring
* **Renal Function:** Monitor BUN and serum creatinine; adjust dose accordingly.
* **Hematology:** CBC with differential if therapy exceeds 10–14 days (risk of neutropenia).
* **Clinical:** Monitor for signs of persistent infection or therapeutic failure.
## Clinical Pearls
* **Stability:** Once reconstituted, solutions are stable for short periods; follow specific IV room temperature/refrigeration guidelines.
* **Sodium Load:** Each 4.5 g dose contains approximately 2.35 mEq of sodium; consider in patients on strict sodium restriction.
* **Empiric Use:** Excellent anaerobic coverage makes it a staple for polymicrobial infections, but it is often overused. Target therapy based on culture results to facilitate antibiotic stewardship.
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*Disclaimer: This information is for educational purposes only. Clinical practice protocols vary by institution. Always consult the most current package insert and your hospital’s antimicrobial stewardship guidelines before prescribing or administering medication.*
