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# Piperacillin/tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia (hospital-acquired pneumonia and ventilator-associated pneumonia)
* Empirical treatment of febrile neutropenia
## Adult Dosing
The typical dose is 3.375 grams every 6 hours or 4.5 grams every 6 or 8 hours intravenously (IV). The dose and frequency depend on the severity and type of infection. Doses are often expressed as piperacillin/tazobactam. For example, 3.375g contains 3g piperacillin and 0.375g tazobactam. For severe infections or those caused by less susceptible organisms, higher doses or more frequent administration may be required, up to 4.5 grams every 4 hours in select cases (e.g., severe hospital-acquired pneumonia, febrile neutropenia).
## Pediatric Dosing
Dosing is weight-based and depends on the indication and patient's age.
* **Patients 13 years and older:** Same as adult dosing.
* **Patients 2 months to 12 years:**
* Complicated intra-abdominal infections: 90-100 mg/kg/day (as piperacillin component) divided every 6 or 8 hours. Maximum daily dose is typically 12 g/day (as piperacillin component), not to exceed adult maximum doses.
* Complicated skin and skin structure infections: 90-100 mg/kg/day (as piperacillin component) divided every 6 or 8 hours. Maximum daily dose is typically 12 g/day (as piperacillin component), not to exceed adult maximum doses.
* **Neonates and infants younger than 2 months:** Dosing is complex and often based on institutional protocols due to immature renal and hepatic function. Typically ranges from 75 mg/kg/day to 100 mg/kg/day divided every 8 or 12 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Reduce maintenance dose frequency to every 8 hours (for 6-hourly regimens) or every 12 hours (for 8-hourly regimens).
* CrCl < 20 mL/min: Reduce maintenance dose frequency to every 12 hours (for 6-hourly regimens) or every 12-24 hours (for 8-hourly regimens).
* For intermittent hemodialysis, administer a dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and injection site reactions. Serious adverse effects include hypersensitivity reactions (anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), and hematologic abnormalities (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** May prolong the duration of neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
* **Aminoglycosides:** Concurrent administration may lead to inactivation of piperacillin. Do not mix in the same IV line.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Signs and symptoms of infection for therapeutic response.
* Signs and symptoms of hypersensitivity reactions.
* Electrolytes, liver function tests, and complete blood count (CBC) periodically, especially with prolonged therapy.
* INR if co-administered with warfarin.
## Clinical Pearls
* Piperacillin/tazobactam is bactericidal and acts by inhibiting bacterial cell wall synthesis.
* Tazobactam protects piperacillin from degradation by beta-lactamase enzymes.
* Reconstituted solutions are stable for a limited time; follow manufacturer or institutional guidelines.
* For patients with penicillin allergy, caution is advised. Cross-reactivity with cephalosporins is possible but less common than with earlier generation cephalosporins.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols for complete and up-to-date guidance.
