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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination penicillin antibiotic and beta-lactamase inhibitor. It has broad-spectrum activity 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 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 8 hours.
* **Severe Infections/Higher Doses:** Doses up to 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 4 hours may be used, particularly for critically ill patients or infections with resistant organisms.
* **Infusion:** Administer over 30 minutes. Extended infusion (over 4 hours) may be considered for certain indications to improve efficacy.
## Pediatric Dosing
* Dosing is highly variable and depends on indication, age, and weight.
* **Neonates and Infants < 3 months:** Typically dosed based on piperacillin component as 50-100 mg/kg/dose every 8-12 hours. Tazobactam is usually added at a 1:8 ratio (e.g., 6.25-12.5 mg/kg/dose). Consult specialized pediatric infectious disease resources for specific recommendations.
* **Children > 3 months:** Typically dosed based on piperacillin component as 75-100 mg/kg/dose every 6 or 8 hours, with tazobactam added at a 1:8 ratio (e.g., 9.375-12.5 mg/kg/dose). Maximum piperacillin dose is generally 4 g per dose and maximum tazobactam dose is generally 0.5 g per dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) or 3.375 g (3 g piperacillin/0.375 g tazobactam) every 8 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) every 8 hours or 2.25 g (2 g piperacillin/0.25 g tazobactam) every 12 hours for higher frequency dosing regimens.
* **Hemodialysis:** Administer a dose after hemodialysis and supplement with an additional 1/4 of the usual dose after each dialysis session. Dosing frequency is typically every 12 hours.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of immediate and severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, pruritus, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, and hepatitis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** Piperacillin may decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels.
## Monitoring
* Assess for signs and symptoms of infection.
* Monitor for adverse effects, particularly hypersensitivity reactions, rash, and diarrhea.
* Monitor renal and hepatic function, especially in patients with pre-existing impairment or receiving high doses.
* Monitor complete blood counts, including platelets, particularly with prolonged therapy.
* Monitor INR in patients receiving warfarin.
## Clinical Pearls
* Piperacillin/tazobactam offers broad-spectrum coverage, making it a valuable agent for empirical therapy in moderate to severe infections.
* Consider de-escalation to narrower-spectrum agents once culture and susceptibility results are available.
* Adjust dose based on renal function.
* Be aware of the potential for cross-reactivity in patients with penicillin allergy.
* Ensure adequate hydration and electrolyte balance, especially in patients with diarrhea.
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*Please verify current prescribing information and institutional protocols before administering this medication.*
