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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia
## Adult Dosing
* **Usual dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously (IV) every 6 hours.
* **Severe infections:** Doses of 4.5 grams IV every 6 hours are often used for severe infections or those caused by less susceptible organisms.
* **Duration of therapy:** Typically 7-14 days. Duration depends on the infection, pathogen, clinical response, and local guidelines.
## Pediatric Dosing
* **Children 2 months to 12 years:**
* **Usual dose:** 90 to 112.5 mg/kg/day (as piperacillin component) administered IV every 6 hours.
* **Maximum:** Total daily dose should not exceed the adult maximum of 12 grams of piperacillin.
* **Neonates and infants younger than 2 months:**
* Dosing is not well established. Use with caution and consider expert consultation. Dosing may be guided by gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* For doses given every 6 hours, the dose should be reduced by one-third and given every 8 hours for CrCl 20-40 mL/min, and by one-half and given every 12 hours for CrCl < 20 mL/min.
* Hemodialysis: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) every 8 hours, with an additional dose after each dialysis.
* **Hepatic Impairment:** No specific guidelines, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of severe allergic reaction (e.g., anaphylaxis) to beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially with impaired renal function or concomitant nephrotoxic agents).
* Liver function tests.
* Complete blood count (may see transient eosinophilia or leukopenia).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile* infection.
## Clinical Pearls
* Piperacillin/tazobactam is typically reconstituted and further diluted for IV infusion over at least 30 minutes.
* The combination targets beta-lactamase producing organisms that would otherwise be resistant to piperacillin alone.
* For febrile neutropenia, guidelines often recommend empiric therapy with piperacillin/tazobactam, often combined with an aminoglycoside and/or vancomycin depending on local resistance patterns and patient risk factors.
* The maximum recommended dose of piperacillin is 18 g per day, and tazobactam is 2.25 g per day.
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*This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for the most current and comprehensive details.*
