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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin-class antibacterial, and tazobactam, a beta-lactamase inhibitor. It is active against many Gram-positive and Gram-negative bacteria, including anaerobes.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia
## Adult Dosing
Standard dose: 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) intravenously every 6 hours.
Extended infusion: 3.375 grams or 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) intravenously every 8 hours, infused over 4 hours. Extended infusion may be associated with improved outcomes in certain serious infections.
Maximum dose: Generally, do not exceed 4.5 grams every 6 hours. For febrile neutropenia, doses up to 4.5 grams every 4 hours have been used, but this depends on local protocols.
## Pediatric Dosing
Dosing varies significantly by indication and patient weight/age. Consult specific pediatric guidelines or institutional protocols.
* **Intra-abdominal infections (3 months to 12 years):** 90 mg/kg (piperacillin component) every 8 hours intravenously, not to exceed 3.375 grams per dose.
* **Hospital-acquired pneumonia (3 months to 12 years):** 90 mg/kg (piperacillin component) every 8 hours intravenously, not to exceed 3.375 grams per dose.
* Doses up to 100 mg/kg (piperacillin component) every 6 hours have been used for severe infections in neonates and infants.
## Dose Adjustments
* **Renal Impairment:**
* CrCl 20-50 mL/min: Reduce dose by 25% or increase interval to every 8 hours.
* CrCl <20 mL/min: Reduce dose by 50% or increase interval to every 12 hours.
* Hemodialysis: Administer usual dose and supplement with an additional 1.125 grams after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but monitor liver function.
## Contraindications
* Known history of severe allergic reaction to penicillins, cephalosporins, beta-lactamase inhibitors, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, elevated liver enzymes (AST, ALT).
* **Serious:** Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea (CDAD), neutropenia, thrombocytopenia, seizures (especially with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Live bacterial vaccines:** Reduced efficacy.
## Monitoring
* Renal function (baseline and periodically, especially with dose adjustments).
* Liver function tests (baseline and periodically).
* Complete blood count (especially with prolonged therapy or suspected hematologic effects).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of CDAD.
* Therapeutic drug monitoring is generally not required but may be considered in specific situations (e.g., severe infections, renal impairment).
## Clinical Pearls
* Always reconstitute and dilute according to manufacturer instructions.
* Administer intravenously over the recommended infusion time to minimize infusion reactions and optimize efficacy (consider extended infusion for severe infections).
* Discontinue if hypersensitivity reactions occur.
* Be vigilant for CDAD, which can occur with almost all antibacterial agents.
* Piperacillin can interfere with certain laboratory tests (e.g., urine glucose assays).
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*Disclaimer: This information is for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information and local institutional guidelines before making any clinical decisions.*
