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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a penicillin-class drug (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is effective against a broad spectrum of aerobic and anaerobic gram-positive and gram-negative 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)
* Nosocomial pneumonia
* Febrile neutropenia (in combination with an aminoglycoside)
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) every 6 hours.
* **High Dose:** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) every 6 or 8 hours. Higher doses or more frequent administration may be considered for severe infections or infections caused by less susceptible organisms, guided by susceptibility data.
* **Duration:** Typically 7 to 14 days.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and depends on the indication and severity of infection. Dosing often occurs every 6 or 8 hours.
* **Children 1 month to 12 years:**
* **Complicated Intra-abdominal Infections:** 90 mg piperacillin / 11.25 mg tazobactam per kg per dose every 6 hours.
* **Community-acquired Pneumonia:** 90 mg piperacillin / 11.25 mg tazobactam per kg per dose every 6 hours.
* **Hospital-acquired Pneumonia:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose every 8 hours.
* **Maximum Dose:** Avoid exceeding the adult maximum daily dose of 18 g (piperacillin) or 1.5 g (tazobactam). Specific maximums per dose vary by indication and age group.
* **Neonates and Infants < 1 month:** Dosing is highly individualized and requires careful consideration of gestational and postnatal age, often with specialized protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 33% to 50% and/or increase interval. Consult prescribing information or institutional guidelines for specific recommendations.
* **Hepatic Impairment:** No dose adjustment is typically required, but caution is advised as piperacillin is eliminated by the liver.
* **Hemodialysis:** Patients on hemodialysis require dose reduction and administration of an additional dose after each dialysis session.
## Contraindications
* Known serious allergic reaction to piperacillin, other penicillins, cephalosporins, beta-lactamase inhibitors, or any component of the formulation.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT), hyponatremia, leukopenia, thrombocytopenia.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome/toxic epidermal necrolysis, seizure, hemolytic anemia, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically)
* Liver function tests (baseline and periodically)
* Complete blood count (baseline and periodically, especially with prolonged therapy)
* Electrolytes (especially sodium)
* Signs and symptoms of infection and superinfection
* Signs and symptoms of hypersensitivity reactions
## Clinical Pearls
* Administer over at least 30 minutes for doses up to 3.375 g, and at least 40 minutes for doses of 4.5 g.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* May be infused concurrently with other intravenous fluids or antibiotics (e.g., aminoglycosides) but should be administered in separate IV lines.
* Consider de-escalation of therapy based on culture and susceptibility results.
* High doses are often necessary for serious infections and may require prolonged infusion times or continuous infusions to achieve adequate therapeutic concentrations.
**Disclaimer:** This information is intended for clinical pharmacists and healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for definitive guidance, as dosing and recommendations can vary.
