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# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and a beta-lactamase inhibitor. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and soft tissue infections (including diabetic foot infections)
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 g every 6 hours or 4.5 g every 6 or 8 hours IV.
* Doses are expressed as grams of piperacillin/tazobactam (e.g., 3.375 g contains 3 g piperacillin and 0.375 g tazobactam).
* Higher doses (e.g., 4.5 g) are often preferred for severe infections, hospital-acquired pneumonia, and infections due to *Pseudomonas aeruginosa*.
* Dosing frequency (every 6 or 8 hours) depends on the severity of illness and desired drug exposure.
## Pediatric Dosing
* **Neonates and infants < 2 months:** Dosing is complex and based on gestational and chronological age. Consult specific pediatric guidelines or pharmacy resources.
* **Children ≥ 2 months:**
* Complicated intra-abdominal infections: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* Other indications: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours or 150 mg piperacillin/18.75 mg tazobactam per kg per dose IV every 8 hours.
* Maximum dose: Generally not to exceed the adult maximum of 4.5 g per dose, or 4 g piperacillin per dose.
* **Important Note:** Dosing in children often requires careful calculation and may vary based on local protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):**
* 3.375 g every 8 hours
* 4.5 g every 8 hours
* **Note:** Further dose reduction may be needed if the patient is on intermittent hemodialysis. Consult pharmacy for specific recommendations.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but caution is advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin, potentially leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels.
* **Live attenuated bacterial vaccines:** Reduced efficacy.
## Monitoring
* Renal function (baseline and periodically, especially in impaired patients or with concurrent nephrotoxic agents).
* Liver function tests.
* Complete blood count (CBC) with differential, especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
## Clinical Pearls
* Piperacillin/tazobactam provides excellent coverage for *Pseudomonas aeruginosa*.
* The addition of tazobactam broadens the spectrum to include many beta-lactamase producing anaerobes and Gram-negative organisms.
* Administer IV infusions over at least 30 minutes to minimize infusion reactions.
* For patients with penicillin allergy, consider the possibility of cross-reactivity with cephalosporins and carbapenems.
* Dosing for severe infections or infections with difficult-to-treat organisms may benefit from extended infusions or continuous infusions. Consult institutional guidelines.
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*Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information, institutional protocols, and a qualified healthcare provider for definitive patient care decisions.*
