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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia (empiric therapy)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 g piperacillin/0.375 g tazobactam) every 6 hours intravenously (IV).
* **Higher Doses for Severe Infections/Pseudomonas:** 4.5 grams (4 g piperacillin/0.5 g tazobactam) every 6 or 8 hours IV.
* **Continuous Infusion (for severe infections/Pseudomonas):** 13.5 grams (12 g piperacillin/1.5 g tazobactam) over 24 hours, administered as a continuous infusion. The daily dose is typically divided into three 4-gram doses (4 g piperacillin/0.5 g tazobactam) every 8 hours, with each dose infused over 30 minutes, followed by a continuous infusion.
* **Maximum Daily Dose:** Typically 18 grams (16 g piperacillin/2 g tazobactam) per day, though higher doses may be used in specific critical care situations. Dosing often depends on local protocols and institutional guidelines.
## Pediatric Dosing
* **Patients 0 to < 2 months:** Dosing is complex and depends on gestational and postnatal age, weight, and indication. Consult specialized pediatric infectious disease resources or protocols.
* **Patients ≥ 2 months:**
* **General Infections:** 100 mg piperacillin per kg per dose every 8 hours IV (maximum 4 g per dose).
* **Severe Infections/Pseudomonas:** 150 mg piperacillin per kg per dose every 6 hours IV (maximum 4 g per dose).
* **Febrile Neutropenia:** 100 mg piperacillin per kg per dose every 8 hours IV (maximum 4 g per dose).
* *Note: Tazobactam dosing is usually based on the piperacillin component (e.g., 12.5 mg tazobactam per kg per dose with 100 mg piperacillin/kg/dose, or 15.6 mg tazobactam per kg per dose with 150 mg piperacillin/kg/dose).*
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment.
* CrCl 20-40 mL/min: 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) every 8 hours.
* CrCl < 20 mL/min: 2.25 g (2g piperacillin/0.25g tazobactam) or 3.375 g (3g piperacillin/0.375g tazobactam) every 12 hours.
* Consider dose reduction and/or increased frequency for higher doses (4.5g) and continuous infusions based on CrCl.
* Hemodialysis: Administer dose after dialysis and supplement with an additional dose.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, cephalosporins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), Stevens-Johnson syndrome, toxic epidermal necrolysis, seizures (especially with renal impairment and high doses), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, anemia), hepatic enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the anticoagulant effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Bacteriostatic Antibiotics:** May potentially antagonize the bactericidal effect of piperacillin/tazobactam.
## Monitoring
* Renal function (baseline and periodically, especially with dose adjustments).
* Liver function tests (baseline and periodically).
* Complete blood count (CBC) with differential and platelet count (especially with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Clinical response to therapy.
## Clinical Pearls
* Piperacillin/tazobactam is often reserved for serious infections due to its broad spectrum and potential for resistance development.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours if refrigerated. Further dilution in infusion fluids is required.
* Always verify the reconstituted and diluted solution compatibility and stability based on the specific manufacturer and intended infusion fluid.
* The beta-lactamase inhibitor tazobactam protects piperacillin from degradation by many beta-lactamases.
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**Disclaimer:** This information is intended for clinical use and does not replace professional judgment. Always consult the most current prescribing information, institutional protocols, and relevant clinical guidelines before administering any medication.
