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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)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
The typical dose is 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) every 6 hours intravenously (IV).
For severe infections or infections caused by less susceptible organisms, doses of 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) every 6 hours or every 8 hours IV may be used.
The maximum daily dose should not exceed 18 grams (piperacillin 16 grams/tazobactam 2 grams).
Duration of therapy is typically 7-14 days, depending on the indication and clinical response.
## Pediatric Dosing
* **Patients 0 to 12 months of age:** Dosing varies significantly based on indication, severity of infection, and gestational/postnatal age. Consult specific pediatric guidelines or institutional protocols. A common starting point for serious infections may be 93.75 mg/kg (piperacillin 80 mg/kg / tazobactam 9.75 mg/kg) every 8 hours IV.
* **Patients 1 to 12 years of age:** Dosing is typically based on piperacillin component.
* **Complicated intra-abdominal infections:** 243.75 mg/kg (piperacillin 200 mg/kg / tazobactam 43.75 mg/kg) every 8 hours IV.
* **Complicated skin and skin structure infections:** 164 mg/kg (piperacillin 135 mg/kg / tazobactam 29 mg/kg) every 8 hours IV.
* **Nosocomial pneumonia:** 243.75 mg/kg (piperacillin 200 mg/kg / tazobactam 43.75 mg/kg) every 6 hours IV.
Maximum pediatric dose should not exceed the adult maximum dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) every 6 hours IV. For higher doses (e.g., 3.375g or 4.5g q6h), administer 3.375g every 8 hours IV.
* CrCl < 20 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) every 8 hours IV.
* Hemodialysis: 2.25 grams (piperacillin 2g/tazobactam 0.25g) every 8 hours IV, with an additional 0.75g dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically necessary.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* Diarrhea
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Fever, phlebitis
* **Serious:** Clostridioides difficile-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with renal impairment or high doses), leukopenia, neutropenia, thrombocytopenia, eosinophilia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of neuromuscular blocking agents.
* **Warfarin:** May decrease the effectiveness of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments)
* Liver function tests
* Complete blood count (CBC)
* Signs and symptoms of infection (clinical response)
* Signs of hypersensitivity reactions
* Clostridioides difficile-associated diarrhea
## Clinical Pearls
* Dosing for pediatric patients can be complex and is often weight-based. Always confirm specific dosing with institutional protocols or pharmacopeial resources.
* Piperacillin/tazobactam can be reconstituted and diluted for IV infusion. Consult the manufacturer's package insert for detailed preparation instructions.
* Rapid infusion can lead to hypersensitivity reactions. Administer as a continuous or intermittent infusion over at least 30 minutes.
* Due to the beta-lactamase inhibitor, tazobactam, this agent has activity against many beta-lactamase-producing organisms.
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*This information is intended for healthcare professionals. Always verify current prescribing information and consult with relevant resources before making clinical decisions.*
