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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and 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 (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (as empiric therapy)
## Adult Dosing
* **Standard Dosing:** 3.375 g (3 g piperacillin/0.375 g tazobactam) or 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously (IV) every 6 hours.
* **Higher Dosing (for severe infections or pathogens requiring higher concentrations):** 4.5 g IV every 4 hours.
* **Maximum dose:** Generally not to exceed 18 g/day (16 g piperacillin/2 g tazobactam). Specific indications and local protocols may dictate maximums.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **2 months to 12 years:** 90 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 or 8 hours, depending on severity and indication. Maximum dose: 4.5 g per dose.
* **Neonates and Infants < 2 months:** Dosing varies significantly by gestational and postnatal age. Consult specific pediatric guidelines or formulary.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard dosing (3.375 g q6h), consider 2.25 g q8h. For higher dosing (4.5 g q4h), consider 3.375 g q8h. For pediatric patients, adjust based on piperacillin dose.
* **Hemodialysis:** Administer the recommended dose during hemodialysis and administer an additional supplemental dose of 0.75 g afterward.
* **Hepatic Impairment:** No dose adjustment necessary.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome/toxic epidermal necrolysis, seizures (particularly at high doses or with renal impairment), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** Prolonged neuromuscular blockade.
* **Warfarin:** May decrease warfarin's anticoagulant effect. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially in patients with renal impairment or those receiving nephrotoxic agents).
* Liver function tests.
* Complete blood count (CBC) with differential and platelet count (especially with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Culture and sensitivity results to guide therapy.
## Clinical Pearls
* Dosing frequency (q6h vs. q4h) and total daily dose depend on the severity of infection, the suspected or proven pathogen, and patient-specific factors like renal function.
* Consider the addition of an aminoglycoside for suspected *Pseudomonas aeruginosa* in severe infections, especially in immunocompromised patients, per local guidelines.
* Reconstitute and dilute according to manufacturer instructions. Infuse over at least 30 minutes.
* Tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing organisms.
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*Disclaimer: This information is intended for healthcare professionals. Always verify current prescribing information with the official product monograph and consult relevant guidelines or literature before making clinical decisions.*
