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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## 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 Dosing:**
* 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 hours.
**Dosage Duration:**
* Typically 7 to 14 days. Duration is dependent on severity of infection, pathogen, and clinical response.
**Maximum Dose:**
* Generally, 4.5 g IV every 6 hours. Higher doses may be used in specific situations such as severe infections or for pathogens with reduced susceptibility, guided by local protocols and susceptibility data.
## Pediatric Dosing
Dosing is typically based on piperacillin component. Tazobactam is dosed proportionally.
* **3 months and older:**
* 9.7 g/m²/day (8 g piperacillin/1.7 g tazobactam) divided into 4 doses (2.44 g/m²/dose), administered IV.
* Alternative dosing based on weight:
* 30 mg/kg/dose (25 mg piperacillin/5 mg tazobactam per kg) IV every 8 hours for mild to moderate infections.
* 40 mg/kg/dose (33.3 mg piperacillin/6.7 mg tazobactam per kg) IV every 6 hours for severe infections.
* Maximum dose in pediatrics is generally capped at the adult equivalent dose of 4.5 g every 6 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) IV every 6 hours. For 4.5 g every 6 hour dosing, use 3.375 g IV every 6 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) IV every 8 hours. For 4.5 g every 6 hour dosing, use 2.25 g IV every 8 hours.
* Dosing in patients on hemodialysis: Administer dose after dialysis and supplement with an additional 0.75 g dose every 24 hours.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Known severe hypersensitivity to piperacillin, other penicillin antibiotics, tazobactam, or any component of the formulation.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, elevated liver enzymes.
* **Serious:** Hypersensitivity reactions (anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with renal impairment and high doses), neutropenia, thrombocytopenia.
## 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:** May decrease the efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* **Renal function:** Essential for dose adjustments.
* **Liver function tests:** Baseline and periodic monitoring.
* **Hematologic parameters:** CBC with differential, platelet count, especially for prolonged therapy.
* **Signs and symptoms of infection:** Clinical response to therapy.
* **Signs of hypersensitivity reactions:** Monitor during and after administration.
* **Signs of *C. difficile*-associated diarrhea:** Diarrhea, abdominal pain, fever.
## Clinical Pearls
* Administer IV infusions over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* Do not mix piperacillin/tazobactam with other medications in the same IV line unless compatibility is established.
* Dosing for specific pathogens (e.g., *Pseudomonas aeruginosa*) or critically ill patients may require higher doses or different dosing frequencies, which should be guided by local protocols and susceptibility testing.
* Sodium content: Each gram of piperacillin contains approximately 0.17 mmol of sodium. For 4.5 g dose, this is ~1.95 grams of sodium. Use with caution in patients requiring sodium restriction.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to ensure patient-specific appropriateness.
