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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It is active against a broad spectrum of gram-positive and gram-negative bacteria, including *Pseudomonas aeruginosa*.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard doses are typically 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) or 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) given intravenously every 6, or sometimes 8, hours.
Dosing for specific indications and severity may vary. For febrile neutropenia, 4.5 grams IV every 6 hours is common.
Maximum daily dose is generally 18 grams (piperacillin 16 g / tazobactam 2 g).
## Pediatric Dosing
Dosing is based on piperacillin component.
* **Children ≥ 2 months:** 90 mg/kg piperacillin component (81 mg/kg piperacillin and 9 mg/kg tazobactam) IV every 6 hours.
* **Maximum dose:** 4.5 grams per dose or 18 grams per day.
* **Neonates and infants < 2 months:** Specific dosing is not established due to immature renal and hepatic function. Consult specialized resources.
## Dose Adjustments
**Renal Impairment (CrCl < 40 mL/min):** Reduce the dose and/or extend the interval.
* For 6-hour interval:
* 3.375 g q6h: Reduce to 2.25 g IV q6h.
* 4.5 g q6h: Reduce to 3.375 g IV q6h.
* For 8-hour interval:
* 3.375 g q8h: Reduce to 2.25 g IV q8h.
* 4.5 g q8h: Reduce to 3.375 g IV q8h.
* **CrCl < 20 mL/min:** May require further reduction or q8h dosing.
* **Hemodialysis:** Administer a supplemental dose (e.g., 1.125 g) after each dialysis session.
**Hepatic Impairment:** Dose adjustment is generally not required, but caution is advised.
## Contraindications
* Known serious allergic reaction to penicillin or cephalosporins.
* Hypersensitivity to piperacillin, tazobactam, or any component of the formulation.
## Adverse Effects
* Diarrhea, nausea, vomiting, rash, pruritus, urticaria, headache.
* Increased liver enzymes (AST, ALT).
* Superinfection (e.g., *Clostridioides difficile*-associated diarrhea).
* Rarely: seizures, interstitial nephritis, Stevens-Johnson syndrome/toxic epidermal necrolysis, hematologic effects (eosinophilia, leukopenia, thrombocytopenia, neutropenia, hemolytic anemia).
## 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 INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (BUN, creatinine) and electrolytes, especially with prolonged therapy or in patients with renal impairment.
* Liver function tests (AST, ALT).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of superinfection, including *C. difficile*.
* Complete blood count (CBC) with differential and platelet count.
## Clinical Pearls
* Piperacillin-tazobactam is a broad-spectrum agent often reserved for more severe infections or those suspected to be caused by resistant organisms like *Pseudomonas aeruginosa*.
* The 4.5 g dose provides a higher ratio of piperacillin to tazobactam (4:1) compared to 3.375 g (8:1).
* Ensure adequate hydration to minimize the risk of crystalluria.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours if at room temperature. Infuse over at least 30 minutes.
* Tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation by many bacterial beta-lactamases.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information, institutional guidelines, and consult with a qualified healthcare provider for diagnosis and treatment.*
