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# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It has broad-spectrum activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
Standard doses are 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, depending on the severity of infection and institution protocol. Higher doses (e.g., 3.375 g or 4.5 g every 4 hours as a continuous infusion) may be used for severe infections or those caused by less susceptible organisms.
## Pediatric Dosing
Dosing is based on piperacillin weight.
* **1 month to 12 years:** 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hours. Maximum dose 4.5 g per dose.
* **12 years and older:** Dosing as per adult guidelines.
## Dose Adjustments
Renal impairment:
* **CrCl ≥ 50 mL/min:** No adjustment needed.
* **CrCl 20-50 mL/min:** Reduce dose frequency to every 8 hours (if on intermittent dosing) or extend the intermittent infusion duration.
* **CrCl < 20 mL/min:** Reduce dose frequency to every 12 hours (if on intermittent dosing) or extend the intermittent infusion duration.
* Hemodialysis: Administer usual dose, followed by an additional dose of 2.25 g (2 g piperacillin/0.25 g tazobactam) after each dialysis.
Dose adjustments for hepatic impairment are not typically required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium. Monitor closely.
* **Warfarin:** Piperacillin may decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically, especially with concomitant nephrotoxic agents).
* Electrolytes.
* Liver function tests.
* Complete blood count (including platelets) with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
## Clinical Pearls
* Continuous infusion may be preferred for severe infections or critically ill patients to maintain higher and more consistent drug concentrations.
* The final reconstituted solution should be infused over at least 30 minutes for intermittent infusions.
* Piperacillin/tazobactam is active against *Pseudomonas aeruginosa*.
* Discontinue if hypersensitivity reaction occurs.
* Consider risk of seizure activity, particularly in patients with renal impairment.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines for complete and up-to-date details.*
