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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor.
## 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
* Aspiration pneumonia
* Infections caused by piperacillin-resistant, beta-lactamase producing Gram-negative bacteria, Gram-positive bacteria, and anaerobes.
## Adult Dosing
* **Standard dose:** 3.375 grams IV every 6 hours.
* **Higher doses for severe infections or suspected resistant organisms:** 4.5 grams IV every 6 hours.
* **Dosing for febrile neutropenia:** 4.5 grams IV every 6 hours.
* **Continuous infusion (alternative for severe infections):** 12 grams/day (4.5 grams every 8 hours) infused over 24 hours.
* **Maximum dose:** Not explicitly defined, but typically based on the higher frequency (every 6 hours) and higher individual dose (4.5 grams).
## Pediatric Dosing
Dosing varies by indication, age, and weight. Consult specific pediatric guidelines or institutional protocols. Examples include:
* **Pediatric patients (≥ 3 months old):**
* **Complicated intra-abdominal infections:** 90 to 112.5 mg piperacillin component/kg/day divided into 3 or 4 doses IV. Maximum daily dose of piperacillin 16 grams/day or 4.5 grams per dose.
* **Hospital-acquired pneumonia:** 90 to 112.5 mg piperacillin component/kg/day divided into 3 or 4 doses IV. Maximum daily dose of piperacillin 16 grams/day or 4.5 grams per dose.
* **Febrile neutropenia:** 90 to 112.5 mg piperacillin component/kg/day divided into 3 or 4 doses IV. Maximum daily dose of piperacillin 16 grams/day or 4.5 grams per dose.
## Dose Adjustments
* **Renal Impairment (CrCl ≤ 40 mL/min):**
* **Standard regimen:** Reduce frequency to every 8 hours.
* **Higher dose regimen (4.5g q6h):** Reduce frequency to every 8 hours.
* **Continuous infusion:** No adjustment needed.
* **Hemodialysis:** Administer after hemodialysis and every 12 hours between sessions. Dose should be adjusted to every 8 hours if CrCl is between 20-40 mL/min.
* **Hepatic Impairment:** No dose adjustment is generally recommended, but caution advised.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, constipation, headache, insomnia, fever, liver enzyme elevations.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with renal impairment or high doses), hematologic effects (neutropenia, thrombocytopenia), interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Methotrexate:** May decrease methotrexate levels.
* **Warfarin:** May decrease the effect of warfarin; increased monitoring of INR is recommended.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** Monitor for hematologic changes.
* **Signs and symptoms of infection:** Clinical response.
* **Signs and symptoms of hypersensitivity reactions.**
* **Stool for *C. difficile* toxin assay** if diarrhea develops.
## Clinical Pearls
* Reconstitute and further dilute for IV infusion. Recommended infusion times are 30 minutes for standard doses and 4 hours for continuous infusion.
* Dosing is based on the piperacillin component. Each 3.375 g vial contains 3 g piperacillin and 0.375 g tazobactam. Each 4.5 g vial contains 4 g piperacillin and 0.5 g tazobactam.
* Consider combination therapy for specific indications (e.g., severe sepsis, suspected MRSA).
* When switching from IV to oral therapy, use an appropriate oral antibiotic based on culture and sensitivity results.
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This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering any medication.
