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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It provides broad coverage against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours or 4.5 grams (4g piperacillin/0.5g tazobactam) every 8 hours intravenously.
* **Febrile neutropenia:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 hours intravenously.
The specific dose and frequency are often guided by local antibiogram data and institutional protocols.
## Pediatric Dosing
* **Intra-abdominal infections, skin and skin structure infections, pneumonia:** 80 mg piperacillin component/10 mg tazobactam component per kg per dose, every 6 hours intravenously. Maximum dose is typically 3.375 grams per dose.
* **Febrile neutropenia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose, every 6 hours intravenously. Maximum dose is typically 4.5 grams per dose.
Dosing in neonates and infants < 3 months is not well-established and requires careful consideration of renal function and clinical status.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 hours (for 3.375g q6h regimens) or every 12 hours (for 4.5g q8h regimens).
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours (for 3.375g q6h regimens) or every 12 hours (for 4.5g q8h regimens).
* Hemodialysis: Administer dose after dialysis and every 12 hours thereafter.
* *Note:* Dose adjustments are based on the piperacillin component.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, anaphylaxis, hypersensitivity reactions, seizures (especially with high doses or renal impairment), interstitial nephritis, neutropenia, thrombocytopenia, leukopenia, hemolytic anemia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests (LFTs).
* Complete blood counts (CBC) for hematologic changes.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* INR if patient is on warfarin.
## Clinical Pearls
* Tazobactam inhibits beta-lactamases, extending the spectrum of piperacillin.
* Reconstitute and dilute according to manufacturer instructions. Administer as a slow intravenous infusion.
* Duration of therapy is typically 7-14 days, depending on the infection, clinical response, and pathogen susceptibility.
* Consider de-escalation to a narrower-spectrum agent once culture and sensitivity results are available and the patient is clinically improving.
* Monitor for potential electrolyte disturbances, especially in patients receiving large volumes of fluid.
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*Disclaimer: This information is intended for healthcare professionals and does not substitute for a thorough review of the current prescribing information, institutional guidelines, and clinical judgment. Always verify current drug information and dosing with official sources before use.*
