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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 (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Bacterial meningitis (if indicated by susceptibility testing)
* Febrile neutropenia
* Other serious infections caused by piperacillin-susceptible or piperacillin-tazobactam-resistant organisms.
## Adult Dosing
Standard dose: 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
Higher doses (e.g., 4.5 grams IV every 6 hours) may be used for severe infections or nosocomial pneumonia, depending on institutional protocol and organism susceptibility.
## Pediatric Dosing
Dosing is based on piperacillin component. Tazobactam is dosed at a fixed ratio to piperacillin.
* **Age < 12 years and weight < 40 kg:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Age < 12 years and weight > 40 kg:** Use adult dosing.
* **Age ≥ 12 years:** Use adult dosing.
* **Neonates and infants < 3 months:** Dosing varies significantly based on gestational and chronological age and renal function. Consult specific pediatric guidelines or institutional protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce frequency. For standard 3.375 g q6h regimen, administer 2.25 g IV every 8 hours. For standard 4.5 g q8h regimen, administer 3.375 g IV every 8 hours. For higher dose regimens, further adjustments are necessary based on specific dose and frequency.
* **Hemodialysis:** Administer dose after hemodialysis and supplement with an additional dose.
* **Hepatic Impairment:** No dose adjustment is typically recommended.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillin derivatives, or beta-lactamase inhibitors.
* History of immediate and severe allergic reaction to penicillin or beta-lactams.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, injection site reaction.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, leukopenia, eosinophilia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests.
* Complete blood count (especially for prolonged therapy).
* Signs and symptoms of hypersensitivity.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Electrolytes.
## Clinical Pearls
* Infusion should be administered over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* For patients with penicillin allergies, careful assessment of the type and severity of the previous reaction is crucial before administration.
* Due to broad spectrum, reserve for indications where it is clearly indicated or as per institutional guidelines to minimize resistance.
* Piperacillin-tazobactam can be reconstituted with sterile water for injection, 0.9% sodium chloride injection, or dextrose 5% injection. Do not use lidocaine as a diluent for IV push.
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**Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. It is a summary and not exhaustive. Always consult the official prescribing information and relevant institutional guidelines for complete details, including potential new warnings, contraindications, and drug interactions. Dosing may vary based on patient-specific factors and local protocols.
