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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many bacterial beta-lactamases, extending its spectrum of activity to include many beta-lactamase-producing Gram-negative 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)
* Bacterial infections caused by piperacillin-susceptible, beta-lactamase-producing *Pseudomonas aeruginosa*
## Adult Dosing
The standard dose is 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 6 hours administered intravenously over 30 minutes.
Higher doses of 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) every 6 hours may be used for more severe infections, particularly those involving *Pseudomonas aeruginosa*.
Maximum daily dose is typically 18 grams (16 grams piperacillin/2 grams tazobactam).
## Pediatric Dosing
* **For patients ≥ 2 months of age:**
* **Intra-abdominal infections:** 100 mg piperacillin component/1.25 mg tazobactam component per kg per dose, administered intravenously every 8 hours.
* **Other infections (e.g., skin and soft tissue, community-acquired pneumonia, febrile neutropenia):** 100 mg piperacillin component/1.25 mg tazobactam component per kg per dose, administered intravenously every 8 hours, OR 75 mg piperacillin component/0.94 mg tazobactam component per kg per dose, administered intravenously every 6 hours.
* Dosing should not exceed the maximum adult dose of 3.375 grams every 6 hours or 4.5 grams every 6 hours, depending on the indication and severity.
* For patients with cystic fibrosis, higher doses may be considered based on clinical response and local protocols.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 50 mL/min: No dose adjustment needed.
* CrCl 20-49 mL/min: 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) every 6 hours. For higher dose regimen, 3.375 grams every 6 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours. For higher dose regimen, 2.25 grams every 8 hours.
* Hemodialysis: Administer the recommended dose every 8 hours and supplement with an additional dose equivalent to the dose administered every 8 hours after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of anaphylactic reaction to beta-lactam antibiotics.
## Adverse Effects
Common adverse effects include diarrhea, rash, nausea, vomiting, headache, insomnia, and injection site reactions.
Serious adverse effects include hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with high doses or renal impairment), and hematologic abnormalities (e.g., neutropenia, thrombocytopenia, eosinophilia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade.
* **Methotrexate:** Piperacillin may reduce methotrexate clearance, increasing toxicity. Monitor methotrexate levels.
* **Oral anticoagulants (e.g., warfarin):** Monitor INR closely as piperacillin may affect platelet function.
## Monitoring
* Assess for signs and symptoms of hypersensitivity reactions, especially during initial doses.
* Monitor for signs and symptoms of *C. difficile*-associated diarrhea.
* Monitor renal function.
* Monitor complete blood counts (CBC) if treatment exceeds 14 days, or in patients with pre-existing hematologic abnormalities.
* Monitor coagulation parameters if co-administered with anticoagulants.
## Clinical Pearls
* Piperacillin/tazobactam is a common empiric choice for serious Gram-negative infections, including *Pseudomonas aeruginosa*.
* Reconstituted solutions should be used within specified timeframes and refrigerated if not used immediately.
* Bacterial counts should be performed before initiating therapy if possible.
* Duration of therapy depends on the severity and type of infection.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols before making any clinical decisions.*
