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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 (cIAI)
* Complicated skin and skin structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Nosocomial pneumonia (HAP)
## Adult Dosing
The standard adult dose is **3.375 g (3 g piperacillin/0.375 g tazobactam) intravenously every 6 hours** or **4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 8 hours**. Dosing is typically based on piperacillin content. Duration of therapy varies by indication and clinical response, usually ranging from 4 to 14 days.
Higher doses, such as **4.5 g intravenously every 4-6 hours**, may be used for severe infections or infections caused by less susceptible organisms. Local protocols should be consulted for specific indications and dosing.
## Pediatric Dosing
Dosing in pediatric patients is based on piperacillin weight and varies by age and indication.
* **Children 2 months to 12 years:** Dosing is typically calculated as **90-100 mg piperacillin equivalent per kg per dose, administered intravenously every 6-8 hours**. The maximum dose should not exceed the adult maximum dose. Specific guidelines for cIAI, cSSSI, and HAP should be consulted.
* **Neonates and Infants < 2 months:** Dosing is less established and requires careful consideration of gestational and postnatal age. Consult specialized pediatric infectious disease resources or local protocols.
## Dose Adjustments
* **Renal Impairment:** Dose reduction and/or increased interval is required for CrCl < 20 mL/min.
* CrCl 20-50 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) IV every 6 hours or 3.375 g IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g IV every 8 hours.
* Hemodialysis: 2.25 g IV every 8 hours, plus an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustments are typically recommended, but caution is advised.
## Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or other components of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, elevated liver enzymes (AST, ALT), hypokalemia.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), anaphylaxis, hypersensitivity reactions, seizures (rare, especially with high doses or renal impairment), neutropenia, thrombocytopenia, prolonged prothrombin time.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests.
* Complete blood count (CBC), especially for prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of CDAD.
* Prothrombin time/INR if co-administered with warfarin.
## Clinical Pearls
* Piperacillin/tazobactam has broad coverage, including *Pseudomonas aeruginosa*.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours if at room temperature.
* The extended infusion (4 hours) may be associated with improved outcomes and lower rates of nephrotoxicity compared to short infusion, especially in critically ill patients. Consult local guidelines for extended infusion protocols.
* Discontinuation of piperacillin/tazobactam should be considered promptly upon confirmation of non-susceptibility or when alternative therapy is appropriate.
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*This information is intended for healthcare professionals. Always consult the current prescribing information and relevant guidelines for complete details and to ensure patient safety.*
