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# Piperacillin-tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a penicillin-class beta-lactam antibiotic, and tazobactam, a 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)
* Empirical treatment of febrile neutropenia (often in combination with an aminoglycoside)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
High dose: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 hours for severe infections or those caused by less susceptible organisms.
Extended-infusion: 3.375 grams or 4.5 grams IV infused over 4 hours every 6 or 8 hours may be considered for improved outcomes in certain patients, particularly those with critical illness. Specific protocols should be followed.
## Pediatric Dosing
Dosing is based on piperacillin component.
* **1 month to 12 years:** 90 to 100 mg piperacillin/kg/day IV divided every 6 or 8 hours. Maximum daily dose: 16 grams piperacillin/2 grams tazobactam.
* **Less than 1 month:** Dosing not well established; use with caution.
* **Cystic Fibrosis:** Higher doses may be used per institutional protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard 3.375g q6h regimen, administer 2.25g q6h. For high dose 4.5g q6h regimen, administer 3.375g q6h. If on hemodialysis, administer the dose every 8 hours and supplement an additional dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment typically needed.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or penicillin.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Hypersensitivity reactions (including anaphylaxis)
* Clostridium difficile-associated diarrhea
* Neutropenia, thrombocytopenia, leukopenia (especially with prolonged therapy)
* Elevated liver enzymes
* Seizures (rare, more common with high doses or renal impairment)
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium. Monitor neuromuscular function.
* **Warfarin:** Beta-lactam antibiotics may decrease the efficacy of warfarin. Monitor INR.
## Monitoring
* Renal function (especially with concomitant nephrotoxic agents)
* Liver function tests
* Complete blood count (CBC) with differential and platelets (especially with prolonged therapy)
* Signs and symptoms of infection resolution
* Signs and symptoms of hypersensitivity reactions
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum agent often used empirically for serious infections.
* Cultures should be obtained before initiating therapy.
* Dosing and frequency adjustment is crucial in patients with renal impairment.
* Extended infusion may be beneficial for critically ill patients or those with severe infections.
* Monitor for signs of C. difficile infection.
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*This information is intended for healthcare professionals. Always consult the current official prescribing information and institutional protocols for complete and up-to-date guidance before making any clinical decisions.*
