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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It is active against many gram-positive, gram-negative, and anaerobic bacteria.
## 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, and nosocomial pneumonia:**
* **Standard dose:** 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours.
* **Maximum dose:** Not explicitly defined, but typically not exceeding 4.5 grams every 6 hours for severe infections.
* **Febrile neutropenia (empiric):**
* **Standard dose:** 4.5 grams IV every 6 hours.
* **Duration:** Typically 7 days or until resolution of neutropenia and fever.
Dosing frequency and duration are often guided by clinical status, severity of infection, and local institutional protocols.
## Pediatric Dosing
Dosing in pediatric patients should be based on total piperacillin component.
* **Children 12 years and younger:** Dosing varies significantly by indication and weight. Consult specific pediatric guidelines.
* **Children 13 years and older:** Similar to adult dosing (e.g., 3.375 grams IV every 6 hours or 4.5 grams IV every 8 hours).
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Dose reduction and/or increased dosing interval required.
* For 3.375 g every 6 hr regimen: Reduce to 2.25 g every 6 hr.
* For 4.5 g every 8 hr regimen: Reduce to 3.375 g every 8 hr.
* **CrCl < 20 mL/min:** Further reduction or extended interval may be necessary.
* **Hepatic Impairment:** No dose adjustment is generally recommended.
Dose adjustments should be made in consultation with prescribing information and renal function.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or any component of the formulation.
* History of allergic reaction to penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, elevated liver enzymes.
* **Serious:** Clostridioides difficile-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), Stevens-Johnson syndrome/toxic epidermal necrolysis, interstitial nephritis, hematologic abnormalities (leukopenia, neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease warfarin's effect. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically, especially in patients with impaired renal function).
* Liver function tests.
* Signs and symptoms of infection resolution.
* Signs of hypersensitivity reactions.
* Blood counts (if prolonged therapy or clinical suspicion).
## Clinical Pearls
* Reconstituted solutions should be used within 24 hours if refrigerated or within 6 hours if at room temperature.
* Consider potential for cross-reactivity in patients with penicillin allergies.
* Monitor for signs of C. difficile infection, especially with prolonged or broad-spectrum antibiotic use.
* Adjust therapy based on culture and sensitivity results when available.
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*Disclaimer: This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional guidelines before making any clinical decisions.*
