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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic (extended-spectrum penicillin) and a beta-lactamase inhibitor. It provides broad-spectrum coverage, including *Pseudomonas aeruginosa*, anaerobes, and many Gram-negative and Gram-positive organisms.
## Primary Indications
Treatment of moderate-to-severe infections including intra-abdominal infections, nosocomial pneumonia, skin and skin structure infections, and sepsis. It is commonly used for empirical coverage of suspected *Pseudomonas*.
## Adult Dosing
Standard dose is 3.375 g (3 g piperacillin / 0.375 g tazobactam) IV every 6 hours.
For serious infections (e.g., *Pseudomonas* or febrile neutropenia), 4.5 g IV every 6 hours is recommended.
Maximum dose: 18 g (piperacillin component) per 24 hours.
## Pediatric Dosing
Patients ≥ 9 months: 100 mg piperacillin/kg per dose IV every 8 hours.
Patients 2–9 months: 80 mg piperacillin/kg per dose IV every 8 hours.
Maximum dose: 4 g piperacillin / 0.5 g tazobactam per dose.
## Dose Adjustments
**Renal Impairment:** Requires adjustment based on CrCl. If CrCl is 20–40 mL/min, use 2.25 g q6h. If CrCl < 20 mL/min, use 2.25 g q8h.
**Hepatic Impairment:** No dosage adjustment indicated.
*Note: Always consult local institutional protocols or nephrology guidelines for specific adjustments in continuous renal replacement therapy (CRRT).*
## Contraindications
History of allergic reactions to any penicillin, cephalosporin, imipenem, or beta-lactamase inhibitor.
## Adverse Effects
Common: Diarrhea, constipation, nausea, headache, injection site reaction.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), rash, blood dyscrasias (leukopenia, thrombocytopenia with prolonged use), and seizure (with high doses in patients with renal failure).
## Key Drug Interactions
* **Probenecid:** Increases serum concentrations of piperacillin.
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro*; do not mix in the same IV line. Administer at separate times.
* **Anticoagulants:** May increase the risk of bleeding due to potential effect on platelet aggregation.
* **Methotrexate:** May increase serum levels of methotrexate.
## Monitoring
* Monitor CBC and differential (risk of neutropenia/thrombocytopenia).
* Assess changes in renal function (Cr, BUN).
* Watch for signs of hypersensitivity (rash, urticaria).
* Monitor for signs of *C. difficile* diarrhea (frequent, foul-smelling stools).
* Monitor electrolytes, specifically sodium (each gram contains ~2.8 mEq of sodium).
## Clinical Pearls
* **Extended Infusion:** In many institutions, extended (prolonged) IV infusion (e.g., 4.5 g over 4 hours) is preferred for critically ill patients to maximize the time the free drug concentration stays above the MIC.
* **Spectrum:** Does not cover methicillin-resistant *Staphylococcus aureus* (MRSA), *Acinetobacter* species, or carbapenem-resistant Enterobacteriaceae (CRE).
* **Staphylococcal impact:** Effective against methicillin-susceptible *S. aureus* (MSSA), but is generally sparing used for MSSA compared to nafcillin/oxacillin.
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**Educational Disclaimer:** This information is for clinical reference and educational purposes only. Always verify drug doses, contraindications, and compatibility with the most current institutional prescribing information, drug monographs, or clinical pharmacists before administration.
