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# Piperacillin/Tazobactam (Zosyn)
## Overview
A fixed-combination extended-spectrum penicillin antibiotic and beta-lactamase inhibitor. It provides broad-spectrum coverage, including *Pseudomonas aeruginosa*, streptococci, enterococci, anaerobes, and many Enterobacterales.
## Primary Indications
Empiric treatment of serious infections including hospital-acquired pneumonia, complicated intra-abdominal infections, skin/soft tissue infections, and febrile neutropenia.
## Adult Dosing
Standard dose is 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
For severe infections (e.g., *Pseudomonas* or nosocomial pneumonia), 4.5 g IV every 6 hours is indicated.
Maximum dose: 18 g (piperacillin component) per day. Infusions should typically be administered over 4 hours (extended infusion) to optimize pharmacodynamics.
## Pediatric Dosing
Patients ≥ 2 months of age: 80–100 mg/kg (piperacillin component) administered every 8 hours.
For febrile neutropenia: 80 mg/kg every 6 hours.
Maximum pediatric dose: 4 g/0.5 g per dose (not to exceed 16 g/2 g per day).
## Dose Adjustments
Renal impairment requires dose reduction based on CrCl. If CrCl is 20–40 mL/min, use 2.25 g every 6 hours. If CrCl < 20 mL/min, use 2.25 g every 8 hours. Supplemental dosing is required post-hemodialysis. Always consult institutional/Lexicomp renal nomograms for precise adjustments.
## Contraindications
Hypersensitivity to piperacillin, tazobactam, or any beta-lactam (due to potential cross-reactivity). History of beta-lactamase inhibitor-associated cholestatic jaundice or hepatitis.
## Adverse Effects
Common: Diarrhea, constipation, nausea, headache, rash.
Serious: *Clostridioides difficile*-associated diarrhea (CDAD), neutropenia (prolonged use), interstitial nephritis, and hypersensitivity reactions (anaphylaxis).
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro*; do not mix in the same solution.
* **Methotrexate:** May increase serum levels of methotrexate; monitor levels.
* **Probenecid:** Increases serum half-life of piperacillin/tazobactam.
* **Warfarin:** Theoretical risk of increased bleeding due to coagulation alterations; monitor INR.
## Monitoring
* Baseline and periodic CBC (especially with prolonged therapy >10 days to monitor for leukopenia/neutropenia).
* Renal function (BUN/Cr) at initiation and during therapy.
* Signs of allergic reaction (rash, wheezing).
* Electrolytes (each 4.5 g vial contains 2.35 mEq of sodium).
## Clinical Pearls
* **Empiric choice:** Generally not the drug of choice for suspected ESBL-producing organisms (Carbapenems are preferred).
* **Extended Infusion:** Prolonged IV infusion (4 hours) is frequently utilized in critically ill patients to keep free drug concentrations above the MIC for a higher percentage of the dosing interval.
* **Stewardship:** High-broad spectrum; switch to narrow-spectrum therapy as soon as culture and sensitivity results are available.
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**Educational Disclaimer:** This information is for educational purposes and does not substitute for professional medical judgment. Always verify dosing and indications against institutional protocols and current prescribing information (package insert).
