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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. This combination extends the spectrum of piperacillin to include many beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (as part of combination therapy)
## Adult Dosing
Standard doses are typically 3.375 grams (3 g piperacillin / 0.375 g tazobactam) or 4.5 grams (4 g piperacillin / 0.5 g tazobactam) intravenously every 6 or 8 hours. The specific dose and frequency depend on the indication, severity of infection, and local institutional guidelines. For severe infections or nosocomial pneumonia, 4.5 grams IV every 6 or 8 hours is often utilized. For febrile neutropenia, continuous infusion may be considered.
## Pediatric Dosing
Dosing in pediatric patients varies by age, weight, and indication.
* **Intra-abdominal infections, skin and skin structure infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours for patients 2 months to 12 years old.
* **Complicated intra-abdominal infections:** 300 mg piperacillin/3.75 mg tazobactam per kg per dose IV every 8 hours for patients 2 months to 12 years old.
* Dosing for neonates and premature infants is not well established and requires careful consideration and may involve different dosing intervals.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is necessary for patients with creatinine clearance (CrCl) < 40 mL/min.
* CrCl 20-40 mL/min: Reduce dose frequency or dose by 25%.
* CrCl < 20 mL/min: Reduce dose frequency or dose by 50%.
* Hemodialysis: Administer usual dose at the end of dialysis and repeat every 8 hours. Supplemental dose of 2.25 g (2 g piperacillin/0.25 g tazobactam) is recommended after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of a severe allergic reaction (e.g., anaphylaxis) to piperacillin, tazobactam, or other beta-lactam agents.
## Adverse Effects
Common adverse effects include diarrhea, rash, nausea, vomiting, headache, insomnia, and eosinophilia. Serious adverse effects include hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures, and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** May decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Electrolytes.
* For patients on warfarin, monitor INR.
* For patients on methotrexate, monitor methotrexate levels.
## Clinical Pearls
* Piperacillin-tazobactam has broad-spectrum activity, including activity against Pseudomonas aeruginosa.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours at room temperature.
* Ensure adequate hydration to minimize the risk of crystalluria.
* The potential for cross-reactivity with other beta-lactam antibiotics exists.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and local institutional guidelines before making clinical decisions.*
