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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with 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
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 g (3 g piperacillin/0.375 g tazobactam) or 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 hours.
Dosing frequency may be increased to every 4 hours for severe infections or specific pathogens.
Maximum daily dose for piperacillin is typically 18 g (24 g piperacillin/3 g tazobactam) divided every 4-6 hours, but consult local protocols.
## Pediatric Dosing
Dosing is based on piperacillin content.
* **3 months to 12 years:** 90 to 100 mg piperacillin/12.5 to 15 mg tazobactam per kg per dose intravenously every 6 or 8 hours. Maximum dose is generally 4.5 g per dose.
* **Over 12 years:** Use adult dosing.
* **Neonates and infants < 3 months:** Dosing is highly variable and depends on gestational and postnatal age. Consult specialized pediatric infectious disease resources or pharmacy for specific recommendations.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment.
* 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) IV every 6 hours.
* CrCl < 20 mL/min: 2.25 g (2 g piperacillin/0.25 g tazobactam) or 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 8 hours.
* Hemodialysis: Administer dose after dialysis and supplement with an additional 1/4 dose.
* **Hepatic Impairment:** No dose adjustment recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to beta-lactam antibiotics.
## Adverse Effects
* Diarrhea
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Fever
* Electrolyte abnormalities (e.g., hypokalemia)
* Elevated liver enzymes
* Rare: Anaphylaxis, Clostridioides difficile infection, seizure (especially with high doses or renal impairment), neutropenia, thrombocytopenia.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (especially if using concurrently with nephrotoxic agents or in patients with pre-existing renal impairment).
* Electrolytes (particularly potassium).
* Signs of C. difficile infection.
* Signs and symptoms of hypersensitivity reactions.
* Liver function tests (baseline and periodically).
* Complete blood count (periodic, especially with prolonged therapy).
## Clinical Pearls
* Reconstitute and dilute per manufacturer's instructions.
* Administer as a continuous infusion for potential improved efficacy in certain severe infections (e.g., sepsis, hospital-acquired pneumonia, MDR pathogens). Consult local protocols for recommended continuous infusion rates.
* The addition of tazobactam broadens the spectrum of activity to include many beta-lactamase producing organisms.
* Ensure adequate hydration in patients with potential for electrolyte imbalance.
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*This information is intended for clinical use and does not replace a thorough review of the most current prescribing information or consultation with a pharmacist or physician. Always verify current dosing and safety recommendations.*
