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# Piperacillin/Tazobactam
## Overview
Piperacillin is a broad-spectrum penicillin antibiotic, and tazobactam is a beta-lactamase inhibitor. This combination broadens the spectrum of activity to include beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams every 6 hours or 4.5 grams every 8 hours, administered as a 30-minute intravenous infusion.
* **Severe Infections (e.g., nosocomial pneumonia, febrile neutropenia):** 4.5 grams every 6 or 8 hours.
* **Dosing depends on infection severity, site, and pathogen susceptibility.**
## Pediatric Dosing
* **Infants and children (older than 3 months):** Dosing is based on the piperacillin component.
* **Mild to moderate infections:** 90 to 100 mg piperacillin/kg/day divided into 3 or 4 doses.
* **Severe infections:** 200 to 300 mg piperacillin/kg/day divided into 3 or 4 doses.
* **Maximum dose:** Generally should not exceed the adult maximum of 4.5 grams per dose.
* **Neonates and infants < 3 months:** Dosing is complex and often based on weight and gestational age; consultation with a pediatric infectious disease specialist or pharmacist is recommended.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams every 6 hours or 3.375 grams every 8 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours or 3.375 grams every 12 hours.
* Hemodialysis: 2.25 grams every 8 hours, with an additional 0.75 grams dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, elevated liver enzymes.
* **Serious:** Anaphylaxis, Clostridioides difficile-associated diarrhea (CDAD), seizures, hypersensitivity reactions, interstitial nephritis, hematologic changes (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, requiring closer INR monitoring.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels closely.
## Monitoring
* Renal function (especially in patients with pre-existing renal impairment or receiving concomitant nephrotoxic agents).
* Liver function tests.
* Complete blood count.
* Signs and symptoms of infection.
* Signs and symptoms of hypersensitivity reactions.
* Stool for C. difficile if diarrhea develops.
## Clinical Pearls
* Piperacillin/tazobactam is typically administered intravenously.
* Duration of therapy should be guided by clinical response, typically 7-14 days for complicated infections.
* For febrile neutropenia, duration is usually 7 days or until resolution of neutropenia and fever.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated, but consult manufacturer's instructions for specific stability data.
* The 4:1 ratio (piperacillin:tazobactam) is the most common formulation.
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any treatment decisions. Dosing regimens may vary based on local protocols and individual patient factors.*
