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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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 (empiric treatment)
* Other serious infections caused by susceptible organisms, including *Pseudomonas aeruginosa*.
## Adult Dosing
Standard dosing is 3.375 g (3 g piperacillin/0.375 g tazobactam) or 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 or 8 hours.
* **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections, Community-Acquired Pneumonia:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours. Duration varies based on infection severity and clinical response (e.g., 7-10 days).
* **Nosocomial Pneumonia:** Often 4.5 g IV every 6 hours is preferred, particularly if *Pseudomonas aeruginosa* is suspected or confirmed.
* **Febrile Neutropenia:** Typically 4.5 g IV every 6 hours. Duration is usually until resolution of neutropenia for at least 2 days and clinical improvement.
Dosing and duration are highly dependent on the specific infection, severity, and patient factors. Consult institutional guidelines for specific protocols.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Children 2 months and older:**
* **Mild to moderate infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Severe infections:** 140 mg piperacillin/17.5 mg tazobactam per kg per dose IV every 8 hours.
* **Maximum dose:** Generally do not exceed 4.5 g per dose.
* **Renal impairment:** Dosing adjustments are necessary.
Specific pediatric dosing may vary and should be confirmed with reliable pediatric dosing resources.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose by 25% or increase interval to every 8 hours.
* CrCl < 20 mL/min: Reduce dose by 50% or increase interval to every 8 hours.
* Hemodialysis: Administer dose after dialysis and supplement with an additional dose during dialysis.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam therapy.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT).
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), anaphylaxis, seizures (especially with high doses or renal impairment), interstitial nephritis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; increased INR monitoring is recommended.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests (baseline and periodically).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Electrolytes, especially if hypokalemia is a concern.
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum agent often used in critically ill patients or for severe infections.
* The addition of tazobactam broadens the spectrum to include many beta-lactamase producing organisms, including some *Pseudomonas aeruginosa* strains.
* Dosing should be guided by institutional antibiogram data and clinical assessment.
* Tazobactam does not inhibit all beta-lactamases; resistance can still occur.
* Ensure adequate hydration to minimize the risk of crystalluria.
* When reconstituting, follow manufacturer instructions for compatible diluents and stability.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before making clinical decisions.
