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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Nosocomial intra-abdominal infections
* Febrile neutropenia (in combination with an aminoglycoside, depending on local guidelines and patient factors)
## Adult Dosing
* **Standard dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) intravenously every 6 hours.
* **High dose for severe infections or nosocomial pneumonia:** 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 hours.
* **Maximum dose:** Dosing is typically capped at the high dose regimen.
## Pediatric Dosing
* **Infections (excluding UTI and CNS infections):** 80 mg piperacillin component/10 mg tazobactam component per kg per dose intravenously every 6 hours.
* Maximum dose: 3.375 g per dose.
* **Febrile neutropenia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose intravenously every 4 hours or 80 mg/10 mg per kg every 6 hours.
* Maximum dose: 4.5 g per dose.
* **UTI and CNS infections:** Dosing is generally higher and frequency may be every 4 or 6 hours. Consult specific pediatric guidelines.
* **Neonates:** Dosing and frequency are highly variable based on gestational and postnatal age. Consult specialized neonatal guidelines.
## Dose Adjustments
* **Renal impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer standard dose every 8 hours.
* CrCl < 20 mL/min: Administer standard dose every 12 hours.
* Dose adjustments should be based on the piperacillin component.
* **Hepatic impairment:** No specific dose adjustment is recommended.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, or other penicillin antibiotics.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, headache, rash, pruritus, insomnia, fever, eosinophilia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (particularly with high doses and renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes.
## 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:** Monitor INR closely as piperacillin may decrease INR.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, BUN)
* Liver function tests (AST, ALT)
* Complete blood count (CBC), especially for prolonged therapy or signs of hematologic toxicity
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile*-associated diarrhea
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
* Tazobactam inhibits many beta-lactamases, extending the spectrum of piperacillin against resistant organisms.
* Administration is typically via intravenous infusion over 30 minutes. For higher doses (4.5 g), infusion over 30-45 minutes is recommended.
* Reconstituted solution should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* The final reconstituted solution should be administered without further dilution.
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**Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant institutional protocols for complete details and to ensure appropriate patient management.
