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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a penicillin-class drug (piperacillin) and a beta-lactamase inhibitor (tazobactam). It has a broad spectrum of activity against many Gram-positive and Gram-negative bacteria, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia:** Typically 3.375 grams every 6 hours or 4.5 grams every 8 hours intravenously. Duration varies by indication and patient response.
* **Nosocomial pneumonia:** Often dosed as 4.5 grams every 6 hours intravenously.
* **Febrile neutropenia:** Commonly 4.5 grams every 6 hours intravenously.
* **Maximum dose:** Doses higher than 4.5 grams every 6 hours are generally not recommended.
## Pediatric Dosing
* **Infants and children (up to 12 years):** Dosing is typically based on piperacillin weight-based dose. A common regimen is 100 mg piperacillin / 12.5 mg tazobactam per kg per dose intravenously every 8 hours. For children with cystic fibrosis or severe infections, doses up to 300 mg piperacillin / 37.5 mg tazobactam per kg per dose intravenously every 6 hours may be used, with a maximum of 4.5 grams per dose.
* **Children 12 years and older:** May be dosed as adults.
Dosing in neonates and younger infants is complex and may require further adjustment based on gestational and postnatal age, renal function, and specific clinical guidelines.
## Dose Adjustments
* **Renal Impairment:**
* If CrCl > 40 mL/min: No adjustment needed.
* If CrCl 20-40 mL/min: Administer usual dose every 8 hours.
* If CrCl < 20 mL/min: Administer usual dose every 12 hours.
* Hemodialysis: Administer usual dose every 12 hours and supplement with an additional 2.25 grams after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillin derivatives, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures (especially with rapid infusion or high doses in renal impairment), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, leukopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for signs of *C. difficile*-associated diarrhea.
* Monitor renal function and electrolytes, especially in patients with pre-existing renal impairment or those receiving nephrotoxic agents.
* Monitor liver function tests.
* Monitor complete blood counts for hematologic changes.
* Monitor INR if co-administered with warfarin.
* Monitor methotrexate levels if co-administered.
## Clinical Pearls
* Piperacillin/tazobactam is often reconstituted with sterile water for injection or 0.9% sodium chloride. Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated. Further dilution is required for IV infusion, typically in 0.9% sodium chloride or dextrose 5%.
* Infusion should generally be over at least 30 minutes to minimize infusion-related reactions. Rapid infusion can increase the risk of seizures.
* The specific ratio of piperacillin to tazobactam is usually 8:1 (e.g., 3.375 g = 3 g piperacillin + 0.375 g tazobactam).
* Consider the spectrum of activity and potential for resistance when selecting empirical therapy.
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*This information is intended for healthcare professionals and does not replace professional clinical judgment. Always verify current prescribing information with the official product monograph or other reliable sources before making clinical decisions.*
