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# Piperacillin-tazobactam
## Overview
Piperacillin-tazobactam is an extended-spectrum penicillin antibiotic in combination with a beta-lactamase inhibitor. It is active 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
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **General Dosing:** Typically 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/Nosocomial Pneumonia:** May require 4.5 grams every 6 hours.
* **Febrile Neutropenia:** 4.5 grams every 6 hours.
* **Maximum Daily Dose:** Doses are generally capped based on piperacillin component, with typical maximums around 18 grams per day (e.g., 4.5 grams every 6 hours). Specific maximums may vary based on indication and patient factors.
## Pediatric Dosing
* **Children less than 12 years:** Dosing is typically based on the piperacillin component, often ranging from 80-100 mg/kg/dose, given every 6-8 hours. The tazobactam component is dosed at a 1:8 ratio to piperacillin. For example, a dose of 100 mg/kg/dose of piperacillin would correspond to 12.5 mg/kg/dose of tazobactam.
* **Neonates and Infants:** Dosing varies significantly by age and weight and requires careful calculation based on prematurity and postnatal age. Consult specific pediatric guidelines.
* **Maximum Dosing:** In children, total daily doses should not exceed the maximum adult daily dose.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 or 12 hours.
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours or reduce the dose itself.
* Hemodialysis: Administer dose at the end of hemodialysis. Dose every 12 hours.
* **Hepatic Impairment:** No specific dose adjustment is generally recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT).
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, hepatitis.
## Key Drug Interactions
* **Aminoglycosides:** Potential for synergistic activity, but co-administration may lead to inactivation of the aminoglycoside by piperacillin. Administer separately.
* **Probenecid:** Increases and prolongs serum concentrations of piperacillin and tazobactam.
* **Neuromuscular blocking agents:** Penicillins may prolong the action of vecuronium and other non-depolarizing neuromuscular blockers.
* **Warfarin:** May decrease the effectiveness of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests (LFTs), especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* Complete blood count (CBC) with differential, especially with prolonged therapy or in patients with neutropenia.
* Culture and sensitivity results to guide therapy.
## Clinical Pearls
* Piperacillin-tazobactam is often reconstituted with sterile water or saline and then further diluted in a compatible IV fluid for infusion. Infusion time is typically 30 minutes.
* Monitor for signs of hypersensitivity, especially in patients with a history of penicillin or cephalosporin allergy.
* Due to its broad spectrum, it can contribute to *C. difficile* infection.
* Dosing for piperacillin-tazobactam is based on the piperacillin component, with tazobactam added in a fixed ratio (e.g., 8:1).
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*This information is intended for clinical use and does not replace a thorough review of the prescribing information or local institutional protocols. Always verify current dosing and safety information with the most recent product labeling and clinical guidelines.*
