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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 (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
* Other serious infections caused by susceptible organisms
## Adult Dosing
The usual adult dose is 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) or 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) administered intravenously every 6 or 8 hours. Dosing frequency and duration depend on the severity of infection and the infecting organism. For severe infections or infections with less susceptible organisms, higher doses or more frequent administration may be necessary. The maximum recommended daily dose is typically 18 g (piperacillin 16 g / tazobactam 2 g).
## Pediatric Dosing
Dosing varies significantly by age and weight.
* **Patients 2 months to 12 years:** Dosing is typically based on piperacillin weight-based dose. For example:
* Complicated intra-abdominal infections: 90 mg piperacillin / 11.25 mg tazobactam per kg per dose, every 8 hours.
* Hospital-acquired pneumonia: 120 mg piperacillin / 15 mg tazobactam per kg per dose, every 6 hours.
* The maximum dose per administration should not exceed the adult dose of 3.375 g or 4.5 g.
* **Neonates and infants younger than 2 months:** Data is limited. Dosing is often guided by expert recommendation or specific institutional protocols, considering gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment necessary.
* CrCl 20-40 mL/min: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) every 8 hours, depending on the prescribed regimen.
* CrCl < 20 mL/min: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) every 12 hours, depending on the prescribed regimen.
* Hemodialysis: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) every 8 hours, and administer an additional dose of 0.75 g (piperacillin 0.675 g / tazobactam 0.075 g) after each hemodialysis session.
## Contraindications
* Known history of severe allergic reaction to piperacillin, tazobactam, other penicillin-class drugs, or beta-lactamase inhibitors.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, and pain at the injection site. Serious adverse effects include hypersensitivity reactions (including 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:** Piperacillin may prolong the action of rocuronium and vecuronium.
* **Warfarin:** Piperacillin may reduce the efficacy of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels.
## Monitoring
* Renal function (serum creatinine) for dose adjustments.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Complete blood count (CBC) for hematologic abnormalities, especially with prolonged therapy.
* Liver function tests (LFTs) if clinically indicated.
* INR if co-administered with warfarin.
## Clinical Pearls
* The reconstitution and dilution of Zosyn require specific steps. Always follow manufacturer instructions or institutional protocols.
* Rapid infusion can cause hypokalemia, fluid overload, and electrolyte disturbances. Infuse over at least 30 minutes.
* Use with caution in patients with a history of allergy to cephalosporins, as there may be cross-reactivity.
* Dosing and duration of therapy should be guided by clinical response and microbiological data.
* For febrile neutropenia, therapy is typically continued until resolution of neutropenia and fever.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for complete details before making clinical decisions.
