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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) every 6 hours intravenously.
* **Higher Dose (for severe infections or Pseudomonas aeruginosa):** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) every 6 or 8 hours intravenously. The 8-hour dosing is typically used for less severe infections or as a step-down therapy.
* **Maximum Dose:** Generally not to exceed 4.5 grams every 6 hours (18 grams daily).
## Pediatric Dosing
* **Patients 2 months and older:** Dosing is based on piperacillin weight-based dose:
* **Complicated intra-abdominal infections:** 100 mg piperacillin/kg/dose every 8 hours. Maximum dose 4 g/dose.
* **Hospital-acquired pneumonia:** 100 mg piperacillin/kg/dose every 8 hours. Maximum dose 4 g/dose.
* **Febrile neutropenia:** 75 mg piperacillin/kg/dose every 6 hours. Maximum dose 4 g/dose.
* Dosing may need further adjustment in very low birth weight infants or neonates. Consult specific pediatric guidelines.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard regimen (3.375 g q6h), administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) every 8 hours. For higher regimen (4.5 g q6h or q8h), administer 3.375 g (piperacillin 3 g / tazobactam 0.375 g) every 8 hours. If patient is on hemodialysis, administer dose every 8 hours and supplement with an additional 0.75 g dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is routinely recommended, but caution is advised.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizure activity (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, leukopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine).
* Liver function tests.
* Complete blood count (especially in prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Culture and sensitivity results to guide therapy.
## Clinical Pearls
* Piperacillin/tazobactam is often used empirically for serious infections due to its broad spectrum, including activity against Pseudomonas aeruginosa.
* Ensure adequate hydration when reconstituting and administering the drug.
* Intermittent infusion is typically over 30 minutes. Extended or continuous infusions may be considered to optimize exposure in certain situations, particularly for P. aeruginosa infections, and may allow for higher daily doses with potentially lower Cmax-related toxicity. Dosing strategies for extended/continuous infusions vary by institution.
* Tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation by many beta-lactamases, widening its spectrum of activity.
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*Please verify this information with the most current prescribing information or institutional protocols before administration.*
