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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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 (empiric treatment)
## Adult Dosing
Standard dose: 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
Higher dose for severe infections or *Pseudomonas*: 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 or 8 hours.
Maximum dose: 18 g per day (16 g piperacillin/2 g tazobactam).
## Pediatric Dosing
Dosing is based on piperacillin component and varies by indication and age/weight.
* **Neonates and infants < 1 month:** Dosing is complex and typically based on gestational and chronological age. Consult specialized pediatric guidelines or pharmacy resources.
* **Children ≥ 1 month:**
* **General infections:** 90-100 mg piperacillin/11.25-12.5 mg tazobactam per kg per dose IV every 6 or 8 hours. Maximum dose: 3.375 g per dose.
* **Complicated intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
* **Febrile neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 6 or 8 hours. Maximum dose: 4.5 g per dose.
Note: Maximum weight-based doses often align with adult doses. Always verify pediatric dosing protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Reduce dose frequency.
* 3.375 g every 8 hours.
* 4.5 g every 8-12 hours.
* If on hemodialysis, administer after dialysis and adjust frequency.
* **Hepatic Impairment:** No specific adjustment recommended, but caution is advised due to potential for accumulation.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* Diarrhea
* Nausea, vomiting
* Rash, pruritus
* Thrombocytosis
* Elevated liver enzymes
* Insomnia
* Headache
* Superinfections (e.g., *C. difficile* diarrhea)
* Hypersensitivity reactions (including anaphylaxis)
* Seizures (more common with high doses or renal impairment)
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance, leading to increased methotrexate levels. Monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments or concomitant nephrotoxic agents).
* Liver function tests.
* Signs of hypersensitivity reactions.
* Signs and symptoms of superinfection.
* Prothrombin time/INR if patient is on warfarin.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many bacterial beta-lactamases.
* Infusion should be administered over at least 30 minutes to reduce the risk of infusion-related reactions.
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours under refrigeration.
* Monitor for electrolyte disturbances, particularly in patients receiving prolonged infusions or with other risk factors.
* Consider dose adjustment based on local antibiograms and specific pathogen susceptibility, especially for *Pseudomonas* infections.
This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional protocols for complete details and to verify dosing and safety before initiating therapy.
