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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with 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
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dosing:** 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.
* **Severe Infections/Pseudomonas aeruginosa:** Higher doses, such as 4.5 grams every 6 hours, are often used.
* **Continuous Infusion:** Recommended for critically ill patients and may allow for higher cumulative doses and improved efficacy. Dosing typically ranges from 13.5 to 18 grams of piperacillin per 24 hours, divided into continuous and bolus doses. Specific protocols vary.
## Pediatric Dosing
* **Neonates and Infants (< 2 months):** Dosing is highly variable and based on gestational and postnatal age. Consult specialized pediatric guidelines.
* **Children (> 2 months):** Dosing is based on piperacillin component.
* **General Infections:** 100 mg/kg/dose (piperacillin equivalent) intravenously every 8 hours.
* ***Pseudomonas aeruginosa* or more severe infections:** 100-150 mg/kg/dose (piperacillin equivalent) intravenously every 6 or 8 hours.
* Maximum dose: 4 g piperacillin per dose.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. Consult specific guidelines for adjusted dosing intervals.
* **Hepatic Impairment:** No dose adjustment is typically required.
* **Hemodialysis:** Administer dose after dialysis and supplement as needed.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Eosinophilia
* Elevated liver enzymes
* Anemia, leukopenia, neutropenia, thrombocytopenia
* *Clostridioides difficile*-associated diarrhea
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Aminoglycosides:** May have synergistic activity, but also potential for antagonism or inactivation in vitro. Separate administration if used concurrently for synergy.
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents:** Piperacillin may prolong the action of vecuronium.
* **Warfarin:** Potential for altered INR; increased monitoring of INR is recommended.
## Monitoring
* Renal function (especially with impaired renal function)
* Liver function tests
* Complete blood count (CBC)
* Signs and symptoms of infection
* Electrolytes
## Clinical Pearls
* The beta-lactamase inhibitor tazobactam broadens the spectrum of activity to include many beta-lactamase-producing organisms.
* Dosing frequency (every 6 vs. 8 hours) depends on the severity of infection and the pathogen.
* Consider continuous infusion for critically ill patients to achieve higher drug concentrations and potentially improve outcomes, particularly against *Pseudomonas aeruginosa*.
* Monitor for hypersensitivity reactions, especially in patients with a history of penicillin or cephalosporin allergy.
* Sodium content: Each gram of piperacillin/tazobactam contains approximately 2.3 mEq of sodium.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols before administering any medication.
