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# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and beta-lactamase inhibitor. It has a broad spectrum of activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria, including Pseudomonas aeruginosa.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Bacterial meningitis (where susceptibility is confirmed)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 g (3 g piperacillin/0.375 g tazobactam) every 6 hours or 4.5 g (4 g piperacillin/0.5 g tazobactam) every 6 or 8 hours IV.
Dosing frequency and duration depend on the type and severity of infection and clinical response.
For severe infections or *Pseudomonas aeruginosa* infections, doses up to 4.5 g every 6 hours may be used.
## Pediatric Dosing
Dosing is based on piperacillin component weight.
* **2 months and older:** 90 mg piperacillin/1.5 mg tazobactam per kg per dose administered intravenously every 6 hours.
* **Maximum single dose:** 4.5 g.
* **For febrile neutropenia:** 90 mg piperacillin/1.5 mg tazobactam per kg per dose administered intravenously every 6 hours.
* **For meningitis:** May require higher doses or more frequent administration based on susceptibility and clinical judgment, though definitive pediatric guidelines are less established. Consult infectious disease specialists.
## 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 or 3.375 g (3 g piperacillin/0.375 g tazobactam) every 8 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) every 8 hours.
* Consider intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT): Administer a dose after each dialysis session. Dose reduction may be needed for CrCl < 20 mL/min. Consult specific CRRT protocols.
## Contraindications
* Known serious allergy to piperacillin, tazobactam, other beta-lactam antibacterials, or any component of the formulation.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT), positive Coombs test.
Serious: Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis.
## 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 warfarin's effect.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl)
* Liver function tests
* Complete blood counts (CBC) with differential, especially with prolonged therapy
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea
* Clinical signs of infection and therapeutic response
## Clinical Pearls
* Reconstituted solutions must be infused over at least 30 minutes.
* Extended infusion (e.g., 4 hours) may be considered for patients with severe infections or those with reduced susceptibility of the pathogen, but evidence is variable. Local protocols should be consulted.
* Tazobactam protects piperacillin from degradation by beta-lactamase enzymes.
* Ensure adequate hydration to minimize the risk of crystalluria.
* Discontinue if hypersensitivity reaction or *C. difficile* colitis occurs.
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This information is intended for healthcare professionals and should not replace consultation of the official prescribing information and current clinical guidelines. Always verify current prescribing information with the manufacturer's package insert or a reliable drug information resource.
