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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, 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
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV).
* **Severe Infections/Nosocomial Infections:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV.
* **Maximum Dose:** Not explicitly defined, but doses up to 4.5g q6h are common in severe infections.
Dosing frequency and duration are dependent on the severity of illness, pathogen susceptibility, and clinical response, often guided by institutional protocols.
## Pediatric Dosing
Dosing for pediatric patients varies significantly by indication and age/weight. General guidelines exist but should be confirmed with specific pediatric dosing resources or institutional protocols.
* **Neonates (0-4 weeks):** Doses are typically lower and more frequent, often based on piperacillin weight-based dosing.
* **Infants and Children (>4 weeks):**
* **Complicated Intra-abdominal Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Nosocomial Pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* **Severe Infections:** May be dosed as 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 hours.
* **Maximum Pediatric Dose:** Typically capped at the adult dose equivalent (e.g., 4.5g per dose) when weight exceeds 50 kg, but specific recommendations can vary.
## Dose Adjustments
* **Renal Impairment:** Dose reduction or increased interval is required for CrCl < 40 mL/min.
* CrCl 20-40 mL/min: 2.25g q6h or 3.375g q8h.
* CrCl < 20 mL/min: 2.25g q8h.
* Consider supplemental doses after hemodialysis.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or other beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** May potentially decrease INR; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (for dose adjustment).
* Signs and symptoms of infection resolution.
* Electrolytes, liver function tests, and complete blood counts periodically, especially with prolonged therapy.
* Signs of hypersensitivity reactions.
* For *Clostridioides difficile* infection if diarrhea develops.
## Clinical Pearls
* Piperacillin/tazobactam provides broad-spectrum coverage, including many resistant organisms like *Pseudomonas aeruginosa*.
* Tazobactam broadens the spectrum of activity by inactivating beta-lactamases.
* Reconstitution and dilution instructions must be followed carefully.
* IV administration only. Infusion time is typically 30 minutes.
* In severe infections, consider the addition of other agents if Gram-negative or Gram-positive resistance is suspected or confirmed.
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_Please verify the current prescribing information for the most up-to-date and comprehensive details._
