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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 bactericidal and effective 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
The typical dose is **3.375 grams every 6 hours** or **4.5 grams every 8 hours**, administered intravenously over 30 minutes. Higher doses may be used for severe infections or in situations requiring higher target concentrations, such as in critically ill patients or infections caused by less susceptible organisms. Specific dosing for critically ill patients or infections requiring higher target concentrations may depend on local institutional protocols.
## Pediatric Dosing
Dosing in pediatric patients (greater than or equal to 3 months) is based on piperacillin weight, typically **80-100 mg piperacillin component per kg per dose** administered every 6 or 8 hours. The maximum dose should not exceed the adult maximum of 4.5 grams per dose. Tazobactam is dosed at **10 mg per kg per dose** concurrently. Dosing for neonates and infants less than 3 months is not established.
## Dose Adjustments
**Renal impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 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 patients: Give a dose every 12 hours and administer an additional dose after each dialysis session.
**Hepatic impairment:** No dose adjustment is generally recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or penicillin.
* History of allergic reactions (e.g., anaphylaxis) to these agents.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, interstitial nephritis, hematologic changes (neutropenia, eosinophilia, thrombocytopenia), liver enzyme elevations.
## 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 effect of warfarin; increased INR monitoring may be necessary.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, increasing toxicity.
* **Bacteriostatic antibiotics (e.g., tetracyclines, chloramphenicol):** May antagonize the effect of piperacillin.
## Monitoring
* Renal function (baseline and periodically, especially in patients with renal impairment).
* Liver function tests.
* Complete blood count, including differential and platelet count.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Signs and symptoms of infection and response to treatment.
## Clinical Pearls
* Piperacillin-tazobactam has a broad spectrum of activity, including many difficult-to-treat pathogens like *Pseudomonas aeruginosa*.
* Reconstituted solution should be used within 24 hours if refrigerated or within 6 hours if at room temperature.
* Monitor for prolonged prothrombin time and bleeding, especially in patients receiving anticoagulants.
* Discontinue if hypersensitivity reaction occurs.
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***Disclaimer:** This information is intended for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information and relevant guidelines for definitive patient care decisions. Verify all dosages and recommendations with up-to-date resources and institutional protocols.*
