Please check your internet connection and try again.
# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. This combination broadens the spectrum of activity of piperacillin against many beta-lactamase producing bacteria.
## Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)
* Bacterial infections in febrile neutropenic patients (in combination with an aminoglycoside)
## Adult Dosing
Standard adult dose is **3.375 g** (piperacillin 3 g / tazobactam 0.375 g) every **6 hours** intravenously (IV). Doses of **4.5 g** (piperacillin 4 g / tazobactam 0.5 g) every **6 hours** IV may be used for more severe infections, particularly HAP/VAP, or those involving *Pseudomonas aeruginosa*.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and severity of infection.
* **Children 2 months and older:**
* **Complicated Intra-abdominal Infections:** 90-100 mg piperacillin / 12.5-15 mg tazobactam per kg per dose every 6 hours IV.
* **Complicated Skin and Skin Structure Infections:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose every 8 hours IV.
* **Febrile Neutropenia:** 90-100 mg piperacillin / 12.5 mg tazobactam per kg per dose every 6 hours IV, often given with an aminoglycoside.
* Maximum pediatric dose generally aligns with the adult dose of 4.5 g every 6 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl 20-80 mL/min: Reduce dose frequency to every 8 hours.
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours and consider reducing dose.
* Dose adjustments should be based on piperacillin component. Hemodialysis removes piperacillin and tazobactam; supplement with one dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
* Diarrhea (most common)
* Rash, pruritus
* Nausea, vomiting
* Headache
* Insomnia
* Eosinophilia, leukopenia, neutropenia, thrombocytopenia
* Elevated liver enzymes
* *Clostridioides difficile*-associated diarrhea (CDAD)
* Anaphylaxis and other severe hypersensitivity reactions
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin-tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the action of vecuronium.
* **Methotrexate:** Piperacillin may decrease methotrexate levels.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Oral contraceptives:** May reduce efficacy. Advise alternative contraception.
## Monitoring
* Renal function (CrCl) for dose adjustment.
* Liver function tests.
* Complete blood count (CBC) with differential and platelet count, especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions and *C. difficile*-associated diarrhea.
* Clinical signs of infection (fever, WBC count, localized signs).
## Clinical Pearls
* Piperacillin-tazobactam is administered via IV infusion. Reconstitution and dilution instructions must be followed carefully.
* For *Pseudomonas aeruginosa* treatment, higher doses (4.5 g IV q6h) and potentially extended infusion times or combination with an aminoglycoside may be considered based on susceptibility and clinical response.
* The efficacy of oral contraceptives may be decreased during and for one cycle after therapy.
* Monitor for signs of electrolyte imbalance, particularly in patients with congestive heart failure or renal impairment, as the formulation contains sodium.
***
*This information is intended for clinical pharmacists and healthcare professionals. Always verify current prescribing information and local protocols before initiating or modifying drug therapy.*
