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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination beta-lactam antibiotic and beta-lactamase inhibitor.
## 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 (3g piperacillin/0.375g tazobactam) intravenously (IV) every 6 hours.
* **Higher Dose (for specific indications like nosocomial pneumonia or severe infections):** 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 hours.
* **Duration:** Typically 7-14 days depending on indication and clinical response.
## Pediatric Dosing
Dosing in pediatric patients varies significantly based on age, weight, and indication. Consult specific pediatric guidelines or institutional protocols.
* **Neonates and Infants (< 3 months):** Dosing is complex and based on gestational and chronological age, often requiring extended infusions. Consult specialized resources.
* **Children (> 3 months) and Adolescents:**
* **Complicated Intra-abdominal Infections:** 90 mg piperacillin component/11.25 mg tazobactam component per kg per dose IV every 6 hours. Maximum dose: 3.375 grams per dose.
* **Other Indications:** May use the same dose or 100 mg piperacillin component/12.5 mg tazobactam component per kg per dose IV every 8 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams IV every 6 hours or 3.375 grams IV every 8 hours.
* CrCl < 20 mL/min: 2.25 grams IV every 8 hours.
* For the 4.5g dose:
* CrCl 20-40 mL/min: 3.375 grams IV every 6 hours.
* CrCl < 20 mL/min: 3.375 grams IV every 8 hours.
* **Hepatic Impairment:** No specific dose adjustment.
* **Hemodialysis:** Dose every 8 hours with an additional dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, abdominal pain, constipation, rash.
* **Serious:** *Clostridioides difficile*-associated diarrhea, anaphylaxis, seizures (especially with renal impairment), Stevens-Johnson syndrome, toxic epidermal necrolysis, hematologic effects (neutropenia, thrombocytopenia, eosinophilia), hepatotoxicity.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Complete blood count with differential and platelet count (especially with prolonged therapy).
* Liver function tests.
## Clinical Pearls
* Administer by IV infusion over 30 minutes. Extended infusions (e.g., 4 hours) may be considered in select patients to optimize efficacy, but this is often based on institutional protocols.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated.
* Piperacillin/tazobactam has broad-spectrum activity, including Pseudomonas aeruginosa, but resistance is increasing.
* Tazobactam extends the spectrum of activity to include many beta-lactamase-producing organisms.
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*This information is intended for healthcare professionals and does not substitute for comprehensive drug information resources or clinical judgment. Always verify current prescribing information with the manufacturer's package insert or other reliable sources before use.*
