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# Piperacillin Tazobactam (zosyn)
## Overview
A combination of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It provides coverage against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
## Primary Indications
Empiric therapy for hospital-acquired pneumonia, intra-abdominal infections, skin and soft tissue infections, and febrile neutropenia.
## Adult Dosing
* **Standard dosing:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* **Severe/Nosocomial infections:** 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours or 8 hours.
* **Maximum dose:** 18 g (piperacillin component) per day.
## Pediatric Dosing
* **Neonates (≤ 9 months):** Dosing is highly age/weight-dependent. Refer to specific institutional neonatal protocols.
* **Infants/Children (≥ 9 months) and Adolescents:** 80–100 mg/kg (piperacillin component) every 6–8 hours.
* **Maximum:** 4 g (piperacillin) per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Requires dose reduction or interval extension. Consult institutional protocols or pharmacopeia (e.g., Lexicomp/Sanford Guide) as adjustments vary significantly based on the degree of impairment and hemodialysis status.
* **Hepatic Impairment:** No standard adjustment required, but use with caution.
## Contraindications
History of hypersensitivity (anaphylaxis) to any penicillin, cephalosporin, or beta-lactamase inhibitor.
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (rash, anaphylaxis), leukopenia/neutropenia (with prolonged use), and seizure activity (high doses in renal failure).
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro*; do not mix in the same IV line. Administer at least 1 hour apart.
* **Probenecid:** Increases serum concentrations of piperacillin/tazobactam.
* **Methotrexate:** Penicillins may decrease renal clearance of methotrexate, increasing risk of toxicity.
* **Warfarin:** Potential for increased INR due to alteration of gut flora; monitor closely.
## Monitoring
* **Renal:** Monitor serum creatinine and urine output.
* **Hematologic:** Monitor CBC with differential (specifically neutrophils) if therapy exceeds 10–14 days.
* **Clinical:** Monitor for signs of allergic reaction, superinfection, or CDAD.
## Clinical Pearls
* **Extended Infusion:** Frequently administered via prolonged infusion (4-hour infusion) to optimize pharmacodynamics (time above MIC) for critically ill patients or MDR organisms.
* **Sodium Content:** Each 4.5 g dose contains approximately 2.35 mEq (54 mg) of sodium; adjust for patients on sodium-restricted diets.
* **Pseudomonas:** Reliable agent for *P. aeruginosa*, but check local antibiograms as resistance patterns vary.
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**Educational Disclaimer:** This information is for educational purposes only. Dosing, particularly in pediatric, renal, or hepatic populations, must be verified against current institutional protocols and the most recent package insert or clinical decision support tools before prescribing or administering.
