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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, and tazobactam, a beta-lactamase inhibitor. It is active against many 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 (including ventilator-associated pneumonia)
## Adult Dosing
The typical dose is 3.375 grams (3g piperacillin / 0.375g tazobactam) intravenously every 6 or 8 hours. Higher doses, such as 4.5 grams (4g piperacillin / 0.5g tazobactam) IV every 6 or 8 hours, may be used for more severe infections or those caused by less susceptible organisms. The duration of therapy depends on the infection severity and clinical response, typically ranging from 7 to 14 days.
## Pediatric Dosing
Dosing in pediatric patients (greater than or equal to 2 months of age) is based on the piperacillin component:
* **Uncomplicated intra-abdominal infections:** 100 mg piperacillin/kg/day divided into 4 doses.
* **Complicated intra-abdominal infections, complicated skin and skin structure infections, community-acquired pneumonia, hospital-acquired pneumonia:** 200 mg piperacillin/kg/day divided into 4 doses.
The maximum daily dose should not exceed the adult maximum of 16 g of piperacillin per day. Tazobactam is administered at a fixed ratio of 1:8 or 1:4 (tazobactam:piperacillin).
## Dose Adjustments
**Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer at the recommended dose every 8 hours.
* CrCl < 20 mL/min: Administer at the recommended dose every 12 hours.
* Hemodialysis: Administer at the recommended dose every 12 hours and supplement with one additional dose after each dialysis session.
## Contraindications
* Known history of severe allergic reaction to penicillin, cephalosporins, beta-lactams, or tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, liver enzyme elevations.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures, interstitial nephritis, hematologic abnormalities.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, leading to toxicity. Monitor methotrexate levels.
* **Warfarin:** May decrease the efficacy of warfarin; monitor INR.
## Monitoring
* Renal function
* Liver function tests
* Complete blood count (especially in prolonged therapy)
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile* infection
## Clinical Pearls
* The reconstituted solution should be administered intravenously over 30 minutes.
* Piperacillin-tazobactam does not provide adequate coverage against *Serratia marcescens* or methicillin-resistant *Staphylococcus aureus* (MRSA).
* Consider local resistance patterns when selecting therapy.
* Monitor for superinfections.
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**Disclaimer:** This information is intended for clinical professionals and does not replace a thorough review of the most current prescribing information, including the full prescribing information and FDA-approved labeling, as well as institutional protocols. Always verify information with reliable sources before making clinical decisions.
