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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, 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
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
## Adult Dosing
* **Complicated intra-abdominal infections, complicated skin and skin-structure infections, community-acquired pneumonia:** Typically 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously every 6 hours.
* **Hospital-acquired pneumonia:** Typically 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 hours.
* **Dosing frequency:** May be increased to every 4 hours for severe infections or infections caused by less susceptible organisms.
* **Maximum daily dose:** Generally 18 grams (piperacillin 16 g / tazobactam 2 g) intravenously per day. Dosing depends on the severity of the infection and the infecting organism.
## Pediatric Dosing
* **Neonates and children up to 12 years of age:** Dosing is based on piperacillin component.
* **1 month to 12 years:** 90 to 100 mg piperacillin component per kg per dose intravenously every 6 to 8 hours. Maximum dose not to exceed 4.5 grams every 6 hours.
* **Less than 1 month:** Dosing recommendations vary. Consult specialized pediatric guidelines. Dosing should be based on gestational and postnatal age.
* **Children over 12 years of age:** Same as adult dosing.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* For intermittent hemodialysis, administer usual dose every 12 hours and administer an additional 2.25 g dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, eosinophilia, positive Coombs test.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures, acute kidney injury, liver damage.
## Key Drug Interactions
* **Probenecid:** May decrease renal clearance of piperacillin-tazobactam, increasing serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium.
* **Oral anticoagulants (e.g., warfarin):** Monitor INR closely; may increase the risk of bleeding.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (serum creatinine, BUN)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC) with differential, especially if therapy is prolonged.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Clinical signs and symptoms of infection.
## Clinical Pearls
* Dosing may vary based on the specific pathogen and local resistance patterns. Always consult institutional guidelines for optimal dosing.
* Piperacillin-tazobactam has a broad spectrum of activity but does not cover all resistant organisms (e.g., MRSA, ESBL-producing organisms without additional agents).
* The duration of therapy should be guided by the severity and type of infection and the clinical response.
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*This information is intended for healthcare professionals. Always verify the most current prescribing information from the manufacturer or other authoritative sources before making clinical decisions.*
