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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 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
* Empirical treatment of febrile neutropenia
## Adult Dosing
Standard dose: 3.375 grams (piperacillin 3 grams/tazobactam 0.375 grams) intravenously (IV) every 6 hours.
High-dose for severe infections (e.g., hospital-acquired pneumonia, febrile neutropenia): 4.5 grams (piperacillin 4 grams/tazobactam 0.5 grams) IV every 6 or 8 hours.
* Continuous infusion dosing is also utilized, often 13.5 grams (piperacillin 12 grams/tazobactam 1.5 grams) per 24 hours, divided into continuous infusion of 3.375 grams every 8 hours or other continuous infusion regimens based on local protocols.
* Maximum daily dose: Generally 18 grams (piperacillin 16 grams/tazobactam 2 grams).
## Pediatric Dosing
* **Children 2 months and older:** Dosing is typically based on the piperacillin component.
* **Complicated intra-abdominal infections:** 100 mg piperacillin/kg/dose IV every 8 hours.
* **Febrile neutropenia:** 100 mg piperacillin/kg/dose IV every 8 hours or 75 mg piperacillin/kg/dose IV every 6 hours.
* **Maximum pediatric dose:** 4.5 grams per dose (equivalent to 4 grams piperacillin).
* Dosing for neonates and infants younger than 2 months is not well established and should be based on specific institutional guidelines or expert consultation.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer standard dose every 8 hours.
* CrCl < 20 mL/min: Administer standard dose every 12 hours.
* Hemodialysis: Administer standard dose every 12 hours and supplement with 2.25 grams after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or beta-lactams.
* History of immediate and severe allergic reaction to penicillins, cephalosporins, or carbapenems.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, injection site reactions.
Serious: Clostridium difficile-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum levels.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; increased monitoring of INR is recommended.
* **Methotrexate:** Piperacillin may decrease methotrexate levels; monitor methotrexate levels closely.
## Monitoring
* Renal function (CrCl) for dose adjustments.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile-associated diarrhea.
* Complete blood count (CBC) with differential and platelet count, especially with prolonged therapy.
* Liver function tests (LFTs) periodically.
* Clinical signs of infection to assess efficacy.
## Clinical Pearls
* Piperacillin/tazobactam is administered via IV infusion. Reconstituted solutions should be diluted further and infused over at least 30 minutes.
* The 3.375 g and 4.5 g formulations contain sodium. Use with caution in patients requiring sodium restriction.
* Tazobactam is a beta-lactamase inhibitor that extends the spectrum of piperacillin to include many beta-lactamase-producing bacteria.
* While effective against many gram-negative organisms, resistance can occur, particularly with Pseudomonas aeruginosa.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and institutional protocols for complete details and to verify current recommendations before use.
