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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, an extended-spectrum penicillin, and tazobactam, 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
* **Standard Dose:** 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) intravenously (IV) every 6 hours.
* **Higher Dose (for severe infections or specific pathogens):** 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) IV every 6 or 8 hours.
* **Maximum Dose:** Generally, not to exceed 18 grams per day (16 grams piperacillin/2 grams tazobactam) for severe infections. Dosing frequency and duration are guided by clinical response and pathogen susceptibility.
## Pediatric Dosing
Dosing is based on piperacillin component and often body surface area (BSA) or weight, with adjustments for renal function. Exact dosing can vary by indication and institutional protocol.
* **Children < 12 years:** Dosing varies significantly. For example, doses of 90-100 mg piperacillin/11.25-12.5 mg tazobactam per kg per dose IV every 6 or 8 hours are used for various infections.
* **Children ≥ 12 years:** Dosed as per adult recommendations.
* **Neonates and Infants < 2 months:** Use with caution, limited data. Dosing is weight-based and adjusted for gestational and postnatal age.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* For doses administered more frequently than every 8 hours (e.g., every 6 hours), reduce the dose by one-third.
* Hemodialysis: Administer usual dose every 8 hours and supplement with an additional dose (one-third of the usual dose) after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is recommended, but caution is advised.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, penicillins, cephalosporins, or other beta-lactams.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia.
* **Serious:** Anaphylaxis, Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with renal impairment and high doses), hypersensitivity reactions, interstitial nephritis, hematologic changes (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin, leading to increased and prolonged serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of neuromuscular blockers.
* **Warfarin:** May decrease the efficacy of warfarin; increased INR monitoring is advised.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically during therapy, especially with higher doses or prolonged courses).
* Liver function tests (baseline and periodically).
* Complete blood count (especially during prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of CDAD.
* Electrolytes.
## Clinical Pearls
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature, depending on the diluent.
* Monitor for therapeutic response and potential adverse effects, especially in patients with renal impairment or those receiving high doses.
* The sodium content can be significant (2.34 mEq per gram of piperacillin), which may be a consideration in patients requiring sodium restriction.
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*This information is intended for healthcare professionals. Please consult the official prescribing information and institutional protocols for complete details and to ensure patient-specific safety and efficacy.*
