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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and effective against a broad range 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
* Febrile neutropenia (empiric treatment)
* Bacterial infections involving *Pseudomonas aeruginosa*
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 to 8 hours.
* **Severe Infections/Pseudomonas Coverage:** Higher doses such as 4.5 grams IV every 6 hours or continuous infusion may be utilized. Dosing and frequency are often guided by institutional protocols, local resistance patterns, and infection severity.
* **Maximum Daily Dose:** Generally not to exceed 18 grams per day.
## Pediatric Dosing
* **Patients 2 months and older:**
* **Body weight ≤ 40 kg:** 90 to 100 mg piperacillin component per kg body weight per dose IV every 6 or 8 hours. Maximum dose: 4.5 grams per dose.
* **Body weight > 40 kg:** Dosing based on adult recommendations (3.375g or 4.5g IV every 6 or 8 hours).
* **Note:** Tazobactam dose is typically 1/8th the piperacillin dose. Dosing should be guided by institutional protocols and renal function.
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Reduce dose and/or increase dosing interval. Consult prescribing information or institutional guidelines for specific adjustments.
* Example: For a patient on 3.375g q8h, may switch to 2.25g q8h, or 3.375g q12h.
* **Hemodialysis:** Administer dose after dialysis and adjust dose and/or interval as needed.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of cholestatic jaundice/hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizure, neutropenia, thrombocytopenia, elevated liver enzymes, acute kidney injury.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease warfarin's anticoagulant effect; increased monitoring of INR is recommended.
* **Methotrexate:** May decrease methotrexate serum levels; increased monitoring may be needed.
## Monitoring
* Renal and hepatic function.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* Complete blood counts (CBC) with differential, especially with prolonged therapy.
* Electrolytes.
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often reserved for more serious infections or when broader coverage is needed.
* Due to the potential for resistance, susceptibility testing is crucial.
* The addition of tazobactam extends the spectrum of activity to include many beta-lactamase producing organisms, including *Pseudomonas aeruginosa*.
* For prolonged infusions (e.g., continuous infusion), stability of the solution needs to be considered.
* Monitor for signs of allergic reaction, especially in patients with a history of penicillin allergy.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information, institutional protocols, and patient-specific factors before making clinical decisions.
