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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.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams every 6 hours intravenously (IV).
* **Higher Dose (for more severe infections, e.g., VAP, febrile neutropenia):** 4.5 grams every 6 or 8 hours IV. The 8-hour dosing is often preferred for continuous infusion.
* **Maximum Dose:** Generally not to exceed 18 grams per day.
## Pediatric Dosing
* **Patients 0 to < 6 months:** Dosing is not well established due to immature renal and hepatic function. Requires careful consideration and may necessitate lower doses and/or extended intervals based on clinical assessment and drug levels.
* **Patients 6 months and older:**
* **Intra-abdominal infections:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 8 hours.
* **Complicated skin and skin structure infections, community-acquired pneumonia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 8 hours.
* **Nosocomial pneumonia, febrile neutropenia:** 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 6 hours. For critically ill children, continuous infusion may be considered with higher total daily doses.
* **Maximum Pediatric Dose:** Not to exceed the adult maximum of 4.5 grams per dose or 18 grams per day. Dosing should not exceed 4 g piperacillin per dose regardless of ideal body weight.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. Standard dose (3.375 g) typically every 8-12 hours. Higher dose (4.5 g) typically every 8-12 hours. Dose adjustments for pediatric patients should follow similar principles based on CrCl.
* **Hemodialysis:** Administer after hemodialysis and supplement with an additional dose.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, elevated liver enzymes (AST, ALT).
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Signs and symptoms of infection resolution.
* Renal function (BUN, creatinine).
* Liver function tests (AST, ALT).
* Complete blood count (CBC), especially in prolonged therapy, to monitor for hematologic changes.
* Electrolytes.
* Signs of hypersensitivity reactions.
* Consider monitoring piperacillin/tazobactam levels in critically ill patients, those with significant renal/hepatic dysfunction, or when therapeutic failure is suspected.
## Clinical Pearls
* Piperacillin/tazobactam is often reconstituted with sterile water for injection and then further diluted in a compatible IV fluid (e.g., 0.9% NaCl, D5W) for infusion. Refer to manufacturer's instructions for reconstitution and dilution.
* Administer IV infusion over at least 30 minutes. Continuous infusion may be beneficial for critically ill patients or those with severe infections to maintain higher drug concentrations and potentially reduce resistance.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of activity against many beta-lactamase producing bacteria.
* Discontinue if hypersensitivity reaction occurs.
* Adjust dose for significant renal impairment.
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*Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the current prescribing information and relevant clinical guidelines for complete and up-to-date details.*
