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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 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
* Nosocomial pneumonia
* Febrile neutropenia
## Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **Severe Infections:** Dosing may be increased to 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours.
* **Duration:** Typically 7 to 14 days, depending on the infection and clinical response.
* **Maximum Daily Dose:** 18 grams (16g piperacillin/2g tazobactam) per day.
## Pediatric Dosing
* **Patients 0 to 12 months:** Dosing is not well established. Refer to specific institutional guidelines or consult infectious disease specialists.
* **Patients >12 months:**
* **Febrile Neutropenia:** 80 mg piperacillin/10 mg tazobactam per kg per dose intravenously every 6 hours.
* **Other Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Maximum Doses:** Individual doses should not exceed 4.5 grams.
* **Renal Impairment:** Dosing adjustments are required.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency to every 8 hours for standard 3.375g doses, or every 12 hours for 4.5g doses. For pediatric patients, adjust dose based on weight and renal function.
* **Hemodialysis:** Administer dose after dialysis and repeat every 8 or 12 hours (depending on dose) thereafter. Supplemental dose of 2.25g (2g piperacillin/0.25g tazobactam) should be given after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam therapy.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), liver enzyme elevations, hematologic changes (neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the efficacy 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*-associated diarrhea.
* Monitor renal function and electrolytes, especially in patients with renal impairment or those receiving concurrent nephrotoxic agents.
* Monitor liver function tests.
* Monitor for signs of superinfection.
* Monitor coagulation parameters if co-administered with warfarin.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, including against *Pseudomonas aeruginosa*.
* The addition of tazobactam protects piperacillin from degradation by many beta-lactamases, extending its spectrum of activity.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Avoid co-administration with bacteriostatic agents, as it may reduce the bactericidal activity of piperacillin/tazobactam.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional protocols for definitive guidance.*
