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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It has broad-spectrum activity 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)
* Febrile neutropenia (as empiric therapy)
## Adult Dosing
The typical adult dose is 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) every 6 hours or 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) every 6 or 8 hours, administered intravenously over at least 30 minutes. Higher doses or more frequent administration may be used for severe infections or infections caused by less susceptible organisms, guided by local protocols and susceptibility data. Duration of therapy is typically 7 to 14 days.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and depends on age and indication.
* **For patients ≥ 12 years of age:** Similar to adult dosing, 3.375 grams every 6 hours.
* **For patients < 12 years of age:**
* **Serious infections:** 100 mg piperacillin/12.5 mg tazobactam per kg of body weight administered every 8 hours intravenously over 30 minutes.
* **Febrile neutropenia:** 75 mg piperacillin/9.375 mg tazobactam per kg of body weight administered every 6 hours intravenously over 30 minutes.
* Maximum dose: 4.5 grams per dose (or 4 grams piperacillin per dose).
* Ensure adequate renal function before dosing.
## Dose Adjustments
**Renal Impairment:**
* CrCl ≥ 50 mL/min: No adjustment necessary.
* CrCl 20-49 mL/min: 2.25 grams (piperacillin 2g / tazobactam 0.25g) every 6 hours or 3.375 grams (piperacillin 3g / tazobactam 0.375g) every 8 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours.
* For patients on intermittent hemodialysis: Administer dose after hemodialysis. Supplemental dose of 0.75 grams is recommended after each dialysis session.
**Hepatic Impairment:** No specific dose adjustments are generally recommended, but caution is advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of previous cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, and eosinophilia.
Serious adverse effects can include Clostridioides difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), leukopenia, neutropenia, thrombocytopenia, elevated liver enzymes, and interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May decrease renal excretion of piperacillin/tazobactam, leading to increased serum concentrations. Monitor for increased toxicity.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade. Monitor for prolonged paralysis.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Monitor for signs and symptoms of hypersensitivity reactions.
* Monitor for signs and symptoms of C. difficile infection.
* Monitor renal function (BUN, creatinine) and liver function tests.
* Monitor complete blood counts (CBC) with differential and platelet counts, especially with prolonged therapy.
* Monitor electrolytes.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many beta-lactamases, extending its spectrum of activity to include many Gram-negative aerobes, anaerobes, and some Gram-positive organisms.
* Dosing should be adjusted based on renal function.
* The total daily dose should not exceed the maximum recommended dose for adults or children, respectively.
* When reconstituting, use only the diluents specified by the manufacturer.
* Infuse intravenously over at least 30 minutes to minimize infusion-related reactions.
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*Please verify this information with the most current prescribing information and relevant institutional protocols before use.*
