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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-type antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against a broad spectrum of Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) intravenously every 6 hours.
* **Higher Dosing:** 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) intravenously every 6 or 8 hours. Dosing every 8 hours is often used for less severe infections or during the maintenance phase.
* **Maximum Dose:** Typically not to exceed 18 grams daily (given as 4.5 grams every 6 hours). Specific maximums can depend on the indication and local protocols.
## Pediatric Dosing
* **Infants and Children (3 months to <12 years):** Dosing is based on the piperacillin component.
* **Complicated Intra-abdominal Infections:** 80 mg piperacillin/10 mg tazobactam per kg per dose intravenously every 6 hours.
* **Complicated Skin and Skin-Structure Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Maximum dose:** Individual doses should not exceed 3.375 grams.
* **Children (≥12 years):** Administer as per adult dosing.
* **Neonates and Infants <3 months:** Dosing is complex and should be guided by specific institutional protocols due to immature renal and hepatic function.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer usual dose every 8 hours.
* CrCl < 20 mL/min: Administer usual dose every 12 hours.
* Hemodialysis: Administer usual dose every 12 hours and supplement with one additional dose during and at the end of each dialysis session.
* **Hepatic Impairment:** Dose adjustments are generally not required; however, close monitoring is advised.
## Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, elevated liver enzymes.
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea (CDAD), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, hemolytic anemia, interstitial nephritis.
## 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; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
* Complete blood count (CBC) with differential and platelet count, especially with prolonged therapy.
* Liver function tests (LFTs).
* Electrolytes.
## Clinical Pearls
* Tazobactam inhibits bacterial beta-lactamases, extending the spectrum of piperacillin to include many organisms that are resistant to piperacillin alone.
* Administer by slow intravenous infusion over at least 30 minutes. Rapid infusion may increase the risk of seizures.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 6 hours at room temperature.
* The sodium content can be significant, especially in patients requiring fluid restriction.
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*Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines before making clinical decisions.*
