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# Piperacillin-tazobactam (Zosyn)
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is bactericidal and has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 g piperacillin / 0.375 g tazobactam) IV every 6 hours.
* **Higher Dose:** 4.5 grams (4 g piperacillin / 0.5 g tazobactam) IV every 6 or 8 hours.
* **Duration:** Typically 7 to 14 days, depending on severity and site of infection. Specific duration often guided by local protocols and clinical response.
## Pediatric Dosing
* **1 month to 12 years:** Dosing is based on piperacillin weight, typically 80-100 mg piperacillin/kg/dose IV every 6 or 8 hours. The ratio of piperacillin to tazobactam is 8:1.
* For example, a dose of 100 mg piperacillin/kg/dose would be approximately 112.5 mg piperacillin-tazobactam/kg/dose.
* **Maximum Dose:** 4.5 grams every 8 hours.
* **Premature Infants (<1 month):** Dosing is complex and depends on gestational and postnatal age. Consult specialized pediatric guidelines.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* **3.375 g every 6 hours:** Reduce to 2.25 grams every 6 hours.
* **4.5 g every 6 hours:** Reduce to 3.375 grams every 6 hours.
* **4.5 g every 8 hours:** Reduce to 3.375 grams every 8 hours.
* A further reduction may be necessary at CrCl < 20 mL/min. Dose adjustment may not be needed for intermittent hemodialysis, but patients should receive an additional dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of severe allergic reaction (e.g., anaphylaxis) to penicillin or cephalosporins.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, eosinophilia, increased liver enzymes.
* **Serious:** Clostridioides difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic abnormalities (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum levels.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine) for dose adjustments.
* Liver function tests (AST, ALT).
* Complete blood count (CBC) for hematologic abnormalities.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Clinical signs of infection for treatment efficacy.
## Clinical Pearls
* Piperacillin-tazobactam has activity against Pseudomonas aeruginosa.
* The tazobactam component extends the spectrum of activity by inhibiting many beta-lactamases.
* Administer IV infusion over at least 30 minutes to reduce the risk of infusion-related reactions.
* Avoid concomitant administration of piperacillin-tazobactam with bacteriostatic agents as it may reduce bactericidal activity.
* Monitor for potential electrolyte disturbances, especially with prolonged therapy or in patients with impaired renal function, as each gram of piperacillin contains approximately 2.3 mEq of sodium.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information, institutional guidelines, and patient-specific factors before making clinical decisions.*
