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# Piperacillin-Tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of a broad-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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)
* Febrile neutropenia (often as part of a broader regimen)
## Adult Dosing
The standard dose is 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. The choice of dose and frequency depends on the severity of infection, suspected pathogens, and local susceptibility patterns. For severe infections, higher doses (4.5g every 6 hours) may be used. The maximum daily dose is typically 18 grams (16g piperacillin/2g tazobactam). Dosing is often guided by institutional protocols.
## Pediatric Dosing
Dosing for pediatric patients varies significantly by age and indication.
* **Patients 13 years and older:** Dosing is the same as adults.
* **Patients younger than 13 years:**
* **Intra-abdominal infections:** 90-100 mg piperacillin component per kg per dose IV every 6 hours. Total daily dose not to exceed 18 g/2.25 g.
* **Complicated skin and skin-structure infections:** 90-100 mg piperacillin component per kg per dose IV every 6 hours. Total daily dose not to exceed 18 g/2.25 g.
* **Complicated urinary tract infections:** 50 mg piperacillin component per kg per dose IV every 6 hours.
* **Bacterial infections (general):** Dosing can range from 45-100 mg piperacillin component per kg per dose every 6 to 8 hours, depending on severity.
**Note:** Specific pediatric dosing should be confirmed with reliable pediatric dosing resources or institutional guidelines, as it can be complex and weight-based. Tazobactam is dosed at 1/8th the piperacillin dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment.
* CrCl 20-40 mL/min: 2.25g or 3.375g every 6 or 8 hours, respectively.
* CrCl < 20 mL/min: 2.25g every 6 or 8 hours.
* Hemodialysis: 2.25g every 8 hours, plus one additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommendations.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
Common adverse effects include diarrhea, rash, nausea, vomiting, headache, insomnia, and elevated liver enzymes (AST, ALT). Serious adverse effects include C. difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), and hematologic abnormalities (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** Increases and prolongs piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin's anticoagulant effect; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (SCr, eGFR) for dose adjustment.
* Liver function tests (AST, ALT) periodically.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Complete blood count (CBC) for potential hematologic changes, especially with prolonged therapy.
* Electrolytes.
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum agent and should be de-escalated to a narrower-spectrum antibiotic when microbiologic data supports it.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated.
* Rapid infusion can lead to hypersensitivity reactions. Infuse over at least 30 minutes.
* The risk of seizures is increased in patients with renal impairment and those receiving high doses.
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***Disclaimer:** This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive guidance.*
