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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV).
* **Higher dose:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 hours IV for more severe infections or those with suspected resistant organisms.
* **Extended-infusion (4 hours):** Often used at 3.375 grams or 4.5 grams every 8 hours IV. Consult institutional guidelines for specific extended infusion dosing.
* Maximum daily dose is generally 18 grams (16g piperacillin/2g tazobactam).
## Pediatric Dosing
* **Patients 0 to 6 months:** Dosing is weight-based and depends on indication and renal function. Consult specialized pediatric guidelines.
* **Patients > 6 months:**
* **Complicated intra-abdominal infections:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 8 hours.
* **Nosocomial pneumonia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 6 hours.
* Maximum dose is 4.5 grams per dose.
## 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 for hemodialysis patients: Administer standard dose every 12 hours and supplement with an additional 2.25 grams dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically required, but monitor liver function tests.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
## Adverse Effects
* Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, elevated liver enzymes, eosinophilia, leukopenia, thrombocytopenia.
* Severe adverse effects include hypersensitivity reactions (anaphylaxis), C. difficile-associated diarrhea, seizures (rare, often with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase 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:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl)
* Liver function tests
* Complete blood count (CBC) with differential
* Signs and symptoms of infection
* Electrolytes
* INR if on warfarin
## Clinical Pearls
* The 3.375 g and 4.5 g formulations are common; ensure correct reconstitution and dilution for IV administration.
* For patients with cystic fibrosis, higher doses and more frequent administration may be necessary.
* Piperacillin/tazobactam is not recommended for patients with penicillin allergy. Consider desensitization if no alternatives exist.
* Tazobactam broadens the spectrum of activity to include many beta-lactamase producing organisms.
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*Disclaimer: This information is intended for clinical pharmacists and should not replace comprehensive drug information resources. Always verify current prescribing information, local protocols, and patient-specific factors before making clinical decisions.*
