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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a broad-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam).
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia (in combination with an aminoglycoside)
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
* **Severe Infections/Institutionally Acquired Infections:** Doses up to 4.5 grams intravenously every 4 hours or continuous infusion may be used.
* **Maximum Daily Dose:** Not explicitly defined, but typically does not exceed 18 grams (16g piperacillin/2g tazobactam) per day.
* **Duration:** Typically 4-14 days, guided by clinical response and institutional protocols.
## Pediatric Dosing
* **Patients ≥ 2 months:** Dosing is based on piperacillin component.
* **2 to < 12 years:** 90 mg piperacillin/11.25 mg tazobactam per kg per dose intravenously every 8 hours.
* **12 years and older:** Dosing as per adult recommendations.
* **Maximum Dose (Pediatric):** 4.5 grams per dose.
* **Note:** Dosing for neonates and infants < 2 months is not well established and requires careful consideration of renal function.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):**
* **3.375 g every 8 hours:** Reduce to 2.25 g every 8 hours.
* **4.5 g every 8 hours:** Reduce to 3.375 g every 8 hours.
* **Continuous Infusion:** Maintain hourly rate, but increase initial loading dose to 4.5g.
* **Hemodialysis:** Administer usual dose, followed by an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution advised due to potential for accumulation in severe liver dysfunction.
## Contraindications
* Known serious allergy to piperacillin, other penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, rash.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** Decreases renal excretion of piperacillin/tazobactam, increasing serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (creatinine, CrCl)
* Liver function tests
* Complete blood count (CBC) with differential and platelets
* Signs and symptoms of infection
* Electrolytes
## Clinical Pearls
* Piperacillin/tazobactam is a potent agent with broad activity, including against *Pseudomonas aeruginosa* and some gram-positive organisms.
* The tazobactam component extends the spectrum of activity against beta-lactamase-producing organisms.
* Dosing and duration of therapy should be guided by institutional antibiograms and clinical response.
* Monitor for signs of hypersensitivity reactions and *C. difficile* infection.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*
