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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including many that are resistant to other beta-lactam antibiotics.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Nosocomial intra-abdominal infections
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **Higher Dose (for more severe infections, e.g., VAP, febrile neutropenia):** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. **Note:** Dosing every 8 hours may be preferred for certain indications or by local protocol.
* **Maximum Dose:** Dosing typically does not exceed 4.5 grams every 6 hours, but this can depend on the specific indication and organism.
## Pediatric Dosing
Dosing is based on the piperacillin component.
* **Children 2 months and older:**
* **2 months to < 12 years or < 40 kg:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 6 hours.
* **≥ 12 years or ≥ 40 kg:** Use adult dosing.
* **Maximum dose for pediatric patients:** Typically 4.5 grams per dose.
* **Neonates and infants < 2 months:** Dosing is not well established. Use with extreme caution and consider pharmacokinetic data.
## Dose Adjustments
* **Renal Impairment:**
* **CrCl > 20 mL/min:** No dose adjustment needed.
* **CrCl ≤ 20 mL/min:** Reduce dose frequency to every 8 hours (for 3.375g dose) or every 12 hours (for 4.5g dose).
* **Hemodialysis:** Administer dose every 8 hours and supplement with an additional dose after each dialysis session.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Elevated liver enzymes (AST, ALT)
* Hypersensitivity reactions (including anaphylaxis)
* Seizures (more common with higher doses or renal impairment)
* Clostridioides difficile-associated diarrhea
## Key Drug Interactions
* **Probenecid:** May increase piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease warfarin effect. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Clinical response to therapy (resolution of infection).
* Electrolytes, especially with prolonged therapy or in patients with renal dysfunction.
## Clinical Pearls
* Administer over at least 30 minutes. Rapid infusion may increase the risk of seizures.
* Reconstituted solution should be used within 24 hours when refrigerated or within 6 hours at room temperature.
* Piperacillin-tazobactam is generally considered broad-spectrum and may contribute to the development of antibiotic resistance. Use should be guided by local antibiograms and susceptibility data when available.
* Consider the risk of cross-reactivity in patients with penicillin allergy, although it is less common with piperacillin compared to other penicillins.
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**Disclaimer:** This information is intended for clinical use and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before administering any medication. Dosing and recommendations may vary based on institutional protocols and individual patient factors.
