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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination of an extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor. It is active against many gram-positive, gram-negative, and anaerobic bacteria, including *Pseudomonas aeruginosa*.
## 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
* **Typical Dose:** 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 6 hours.
* **Severe Infections/Pseudomonas Infections:** 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 or 8 hours.
* **Maximum Dose:** Generally not to exceed 18 grams per day (e.g., 4.5 grams every 4 hours), depending on indication and renal function.
Dosing frequency and duration are guided by the severity of illness, pathogen susceptibility, and clinical response.
## Pediatric Dosing
* **Children < 2 months:** Dosing is highly variable and depends on gestational age, postnatal age, weight, and indication. Consult specialized pediatric infectious disease resources.
* **Children ≥ 2 months:**
* **Body weight ≤ 40 kg:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose intravenously every 6 hours.
* **Body weight > 40 kg:** Use adult dosing.
* **Maximum Pediatric Dose:** Doses generally do not exceed the adult maximum of 4.5 grams per dose.
## Dose Adjustments
* **Renal Impairment:**
* **CrCl > 40 mL/min:** No adjustment needed.
* **CrCl 20-40 mL/min:** 2.25 grams (piperacillin 2 grams / tazobactam 0.25 grams) or 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 8 hours.
* **CrCl < 20 mL/min:** 2.25 grams (piperacillin 2 grams / tazobactam 0.25 grams) intravenously every 8 hours.
* **Hemodialysis:** Administer dose after hemodialysis and adjust frequency to every 8 hours.
## Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or beta-lactams.
## Adverse Effects
* Diarrhea
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Increased liver enzymes (AST, ALT)
* Hypersensitivity reactions, including anaphylaxis
* *Clostridioides difficile*-associated diarrhea
* Seizures (rare, more common with high doses or renal impairment)
* Hematologic changes (neutropenia, thrombocytopenia)
## 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:** Piperacillin-tazobactam may decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin-tazobactam may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Signs and symptoms of infection resolution.
* Renal function (especially with CrCl < 40 mL/min).
* Liver function tests.
* Complete blood count (CBC), including platelets.
* Signs of hypersensitivity reactions.
* Electrolytes.
* INR if co-administered with warfarin.
## Clinical Pearls
* The reconstitution and dilution instructions are critical for achieving the correct concentration and ensuring stability. Infusion rates are also important to minimize infusion-related reactions.
* Piperacillin-tazobactam is often used for suspected or confirmed *Pseudomonas aeruginosa* infections.
* Discontinue if hypersensitivity reaction occurs.
* Superinfections may occur.
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*Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult the most current prescribing information and refer to institutional protocols or a qualified healthcare provider for definitive guidance.*
