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## Overview
Piperacillin/tazobactam (Zosyn) is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor.
## Primary Indications
Treatment of moderate to severe infections caused by piperacillin-susceptible organisms, including those producing beta-lactamase, in the following areas:
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Uncomplicated skin and skin-structure infections
* Febrile neutropenia (empiric treatment)
* Bacterial meningitis (when other agents are not suitable)
## Adult Dosing
The usual dose is 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 6 hours or 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) every 6 or 8 hours intravenously. Duration of therapy is typically 7 to 14 days, depending on the infection severity and patient response.
## Pediatric Dosing
For children from 2 months to 12 years of age:
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg body weight administered every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg body weight administered every 8 hours.
* **Hospital-acquired pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg body weight administered every 8 hours.
For children less than 2 months of age, dosing is not well established and should be based on institutional guidelines or expert consultation. The maximum dose in children should not exceed the adult dose of 4.5 grams every 6 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) every 6 hours. For the 4.5 g formulation, administer 3.375 g (3 g piperacillin/0.375 g tazobactam) every 6 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) every 8 hours. For the 4.5 g formulation, administer 2.25 g (2 g piperacillin/0.25 g tazobactam) every 8 hours.
* **Hemodialysis:** Administer the usual dose and supplement with an additional dose (2.25 g) after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustments are recommended, but caution should be exercised.
## Contraindications
* Known severe allergic reaction (e.g., anaphylaxis) to piperacillin, tazobactam, other penicillins, or beta-lactam antibacterial agents.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and abdominal pain. Serious adverse effects include hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), and hematologic changes.
## Key Drug Interactions
* **Aminoglycosides:** Concurrent use may lead to inactivation of piperacillin; administer separately.
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade 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 (especially with concomitant nephrotoxic agents).
* Electrolyte balance.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Bleeding parameters if co-administered with warfarin.
* Neurological status for signs of seizures.
* Blood counts, liver function tests, and coagulation parameters may be monitored periodically.
## Clinical Pearls
* The reconstituted solution must be further diluted for intravenous infusion.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours when refrigerated.
* Monitor for signs of hypersensitivity reactions throughout treatment.
* Discontinue if a severe hypersensitivity reaction occurs.
* If a patient develops diarrhea, consider C. difficile-associated diarrhea.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering any medication.*
