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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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)
* Empirical treatment of febrile neutropenia
## Adult Dosing
Standard dose: 3.375 g (piperacillin 3 g / tazobactam 0.375 g) every 6 hours IV.
Higher dose: 4.5 g (piperacillin 4 g / tazobactam 0.5 g) every 6 or 8 hours IV.
* Dosing frequency and total daily dose may vary based on indication and severity of infection. Consult local protocols for specific indications such as febrile neutropenia or severe hospital-acquired pneumonia.
* Maximum daily dose: 18 g (piperacillin 16 g / tazobactam 2 g) divided every 6 or 8 hours.
## Pediatric Dosing
Dosing is based on piperacillin component and adjusted for renal function.
* **Patients 0 to < 6 months:** Limited data available. Dosing is complex and usually guided by specialist.
* **Patients ≥ 6 months:**
* **Complicated intra-abdominal infections:** 300 mg piperacillin/kg/day divided every 8 hours IV.
* **Other indications:** 300 mg piperacillin/kg/day divided every 6 or 8 hours IV.
* **Febrile neutropenia:** 100 mg piperacillin/kg/dose every 8 hours IV.
* **Maximum dose:** Generally not to exceed 4 g piperacillin per dose. For febrile neutropenia, consult specific guidelines.
## Dose Adjustments
* **Renal Impairment (CrCl ≥ 50 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl 20-49 mL/min):**
* Standard dose (3.375 g q6h): Increase interval to every 8 hours.
* Higher dose (4.5 g q6h): Increase interval to every 8 hours.
* Higher dose (4.5 g q8h): Increase interval to every 12 hours.
* **Renal Impairment (CrCl < 20 mL/min):**
* Standard dose (3.375 g q6h): Give 2.25 g every 8 hours.
* Higher dose (4.5 g q6h): Give 3.375 g every 8 hours.
* Higher dose (4.5 g q8h): Give 3.375 g every 12 hours.
* **Hemodialysis:** Dose administered should be followed by an additional dose of 2.25 g (piperacillin 2 g/tazobactam 0.25 g) after each dialysis period.
* **Hepatic Impairment:** No specific guidance, use with caution.
## Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, other beta-lactams, or penicillins.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, hypokalemia, elevated liver enzymes.
* **Serious:** Anaphylaxis and other severe hypersensitivity reactions, *Clostridioides difficile*-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis, drug fever.
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin and increase serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of neuromuscular blocking agents.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease the clearance of methotrexate. Monitor methotrexate levels.
* **Bacteriostatic agents (e.g., tetracyclines, macrolides):** May antagonize the bactericidal effect of penicillins.
## Monitoring
* Signs and symptoms of infection.
* Renal and hepatic function.
* Electrolytes (especially potassium).
* Complete blood count (CBC) for hematologic changes.
* Signs of hypersensitivity or allergic reactions.
* Signs of *C. difficile* infection.
## Clinical Pearls
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Monitor for development of penicillin resistance.
* May cause a false-positive Coombs test.
* Ensure adequate hydration to minimize the risk of crystalluria.
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*Please verify the current prescribing information for complete details and any updates before making clinical decisions.*
