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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor. It has a broad spectrum of activity against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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)
* Febrile neutropenia (as empiric therapy)
## Adult Dosing
Standard adult doses are typically based on piperacillin content:
* **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 or every 8 hours**
Dosing frequency and duration depend on the type and severity of infection, as well as clinical response. Higher doses (e.g., 4.5 g IV every 6 hours) or extended infusions may be considered for severe infections or pathogens requiring higher drug concentrations, such as *Pseudomonas aeruginosa*.
## Pediatric Dosing
Dosing is based on piperacillin content and patient weight. Recommended doses vary by indication and age:
* **Neonates and Infants (0-3 months):** Dosing is complex and often based on weight and gestational age. Consult specialized pediatric guidelines. A common starting point might be 75 mg piperacillin/kg/day divided every 8-12 hours.
* **Children (3 months to 12 years):** Doses generally range from 240-300 mg piperacillin/kg/day divided every 6-8 hours. For example, 90 mg piperacillin/kg/dose (delivering 80 mg piperacillin and 10 mg tazobactam per kg) administered every 6 hours.
* **Children >12 years:** Dosing often mirrors adult dosing, 3.375 g or 4.5 g IV every 6 or 8 hours.
**Note:** Specific pediatric dosing can depend on local protocols and the severity of infection.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: Reduce dose frequency to every 8 hours.
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours.
* Hemodialysis: Administer dose after hemodialysis and reduce frequency to every 12 hours.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate and severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, liver enzyme elevations.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, typically with high doses or renal impairment), interstitial nephritis, hematologic abnormalities (e.g., 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:** Piperacillin-tazobactam may decrease the effectiveness of warfarin, leading to an increased risk of clotting. Monitor INR closely.
* **Methotrexate:** Piperacillin-tazobactam may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically, especially in those with risk factors).
* Liver function tests (periodically).
* Complete blood count (periodically, especially with prolonged therapy).
* Signs and symptoms of infection and clinical response.
* Signs of hypersensitivity reactions.
* INR if co-administered with warfarin.
## Clinical Pearls
* Piperacillin-tazobactam is often reserved for more serious infections due to its broad spectrum and potential for resistance development.
* Administer by IV infusion over at least 30 minutes. Extended infusions (e.g., over 4 hours) may be beneficial for achieving higher and more consistent drug concentrations, particularly against *Pseudomonas aeruginosa*.
* When reconstituting, use the provided diluent or compatible solutions (e.g., sterile water for injection, normal saline). Avoid solutions containing sodium bicarbonate.
* The reconstituted solution is stable for a limited time; follow manufacturer instructions.
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*Please verify current prescribing information and institutional protocols for the most up-to-date recommendations.*
