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# Piperacillin-Tazobactam (Zosyn)
## Overview
A fixed-combination extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor. It provides coverage against Gram-positive, Gram-negative, and anaerobic organisms, including *Pseudomonas aeruginosa*.
## Primary Indications
Empiric therapy for hospital-acquired pneumonia, intra-abdominal infections, skin and skin structure infections, and sepsis. Often used as a broad-spectrum "workhorse" antibiotic in inpatient settings.
## Adult Dosing
* **Standard dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* **Severe infections (P. aeruginosa):** 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours.
* **Extended infusion:** 4.5 g IV infused over 4 hours every 8 hours is common in institutional protocols to optimize pharmacodynamics.
## Pediatric Dosing
* **General infection (≥ 9 months):** 80–100 mg/kg (based on piperacillin component) IV every 8 hours.
* **Maximum dose:** 4 g piperacillin per dose (4.5 g total combination).
* *Note: Always verify unit-specific protocols, as pediatric dosing is frequently weight-based and indication-dependent.*
## Dose Adjustments
* **Renal Impairment:** Requires significant reduction based on CrCl. Use 2.25 g to 3.375 g every 8–12 hours depending on the degree of impairment.
* **Hemodialysis:** Administer supplemental dose (0.75 g) post-dialysis.
* *Consult institutional renal dosing guidelines or pharmacists for specific CrCl breakpoints.*
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics (e.g., cephalosporins, carbapenems).
* History of severe allergic reactions (e.g., anaphylaxis, SJS/TEN) to any beta-lactam.
## Adverse Effects
* **Gastrointestinal:** Diarrhea (risk of *C. difficile*-associated diarrhea).
* **Hematologic:** Reversible leukopenia, neutropenia, and thrombocytopenia (especially with prolonged therapy > 14 days).
* **Renal:** Possible increased rate of acute kidney injury (AKI), particularly when combined with vancomycin.
* **Other:** Rash, infusion site reactions, and elevated liver enzymes.
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides (e.g., gentamicin, tobramycin). Administer at least 1 hour apart.
* **Probencid:** Decreases renal excretion; increases piperacillin levels.
* **Methotrexate:** May increase methotrexate toxicity by decreasing renal clearance.
* **Warfarin:** Theoretical increased risk of bleeding (hypoprothrombinemic effect of high-dose penicillins).
## Monitoring
* **Renal function:** Monitor BUN and serum creatinine, especially in patients with baseline impairment.
* **Hematology:** CBC with differential weekly during prolonged therapy to monitor for neutropenia.
* **Infection:** Monitor clinical signs (fever, WBC count, site-specific symptoms).
* **C. difficile:** Monitor for frequency of stools or signs of colitis.
## Clinical Pearls
* **Stability:** Administer via slow IV infusion (usually 30 minutes to 4 hours).
* **Pseudomonal Coverage:** Highly effective; however, screen for institutional resistance patterns (antibiograms).
* **Sodium Load:** Each 4.5 g dose contains approximately 235 mg (10.2 mEq) of sodium, which may be clinically significant in patients with CHF or hypertension.
* **Culture Directed:** De-escalate therapy based on susceptibility reports to minimize antimicrobial pressure.
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**Educational Disclaimer:** This information is for educational purposes only. Clinical practices vary by institution. Always verify current prescribing information, institutional protocols, and patient-specific factors via reliable pharmacological resources (e.g., Lexicomp, UpToDate) before administering medication.
