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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
Standard dose: 3.375 grams (3 grams piperacillin / 0.375 grams tazobactam) IV every 6 hours.
High-dose for *Pseudomonas* or severe infections: 4.5 grams (4 grams piperacillin / 0.5 grams tazobactam) IV every 6 or 8 hours.
Extended-infusion: 3.375 grams or 4.5 grams infused over 4 hours every 6 or 8 hours may improve efficacy, particularly against *Pseudomonas aeruginosa*.
## Pediatric Dosing
Dosing is typically based on piperacillin component.
* **1 month to 12 years:**
* Complicated intra-abdominal infections: 90-100 mg piperacillin/kg/dose IV every 8 hours.
* Complicated skin and skin structure infections: 90-100 mg piperacillin/kg/dose IV every 8 hours.
* Hospital-acquired pneumonia: 90-100 mg piperacillin/kg/dose IV every 8 hours.
* Maximum dose: 4 grams piperacillin/dose.
* **Neonates (<1 month):** Dosing is complex and often guided by specific protocols due to immature renal function. Generally, doses are lower and given more frequently. Consult specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No dose adjustment needed.
* CrCl 20-39 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) IV every 6 hours or 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) IV every 8 hours.
* Dosing for **high-dose regimens** in renal impairment will also require adjustments. Specific guidelines should be consulted.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* Diarrhea (common)
* Rash
* Nausea, vomiting
* Headache
* Insomnia
* Fever
* Thrombocytopenia, leukopenia, eosinophilia (reversible)
* Increased serum creatinine and BUN
* *Clostridioides difficile*-associated diarrhea
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (serum creatinine, BUN)
* Liver function tests
* Complete blood count (CBC), especially with prolonged therapy
* Signs and symptoms of infection resolution
* Electrolytes
## Clinical Pearls
* When using high doses for *Pseudomonas* or severe infections, consider extending the infusion time to 4 hours to achieve higher area under the curve (AUC) and improve outcomes.
* Risk of hypersensitivity reactions, including anaphylaxis, is present. Ensure patient has no history of penicillin allergy.
* Superinfection with resistant organisms, including *Candida*, may occur.
* Monitor for signs of *C. difficile*-associated diarrhea.
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*Please verify current prescribing information and institutional protocols for the most up-to-date and specific guidance.*
