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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination of a penicillin-class antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is active against a broad spectrum of Gram-positive and Gram-negative bacteria, including many anaerobes.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard adult doses:
* 3.375 grams every 6 hours intravenously.
* 4.5 grams every 6 or 8 hours intravenously.
Maximum daily dose is typically 18 grams. Duration of therapy depends on the indication and clinical response.
## Pediatric Dosing
Dosing is based on piperacillin content:
* **1 month to 12 years:** 100 mg/kg/dose piperacillin every 8 hours or 90 mg/kg/dose piperacillin every 6 hours intravenously.
* **Greater than 12 years:** Dosing is the same as adults.
Maximum doses should not exceed adult maximums. Specific guidelines for neonates (<1 month) may vary and require careful consideration of renal and hepatic immaturity.
## Dose Adjustments
* **Renal Impairment:** Adjust dose based on calculated creatinine clearance. For example, a patient with a CrCl of 20-50 mL/min may receive 2.25g or 3.375g every 8 hours, and a CrCl <20 mL/min may receive 2.25g or 3.375g every 12 hours. Dosing frequency reduction is common.
* **Hepatic Impairment:** No specific dose adjustment is routinely recommended, though caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
## Adverse Effects
* Diarrhea (most common)
* Rash
* Nausea, vomiting
* Headache
* Insomnia
* Eosinophilia
* Increased AST/ALT
* Thrombocytosis, decreased platelet count
* Hypokalemia
* Rare: Seizures (especially at high doses or in renal impairment), Clostridioides difficile-associated diarrhea, Stevens-Johnson syndrome/toxic epidermal necrolysis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin and tazobactam.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Renal function (creatinine clearance for dose adjustment)
* Liver function tests (AST, ALT)
* Electrolytes (especially potassium)
* Complete blood count (platelets, eosinophils)
* Signs and symptoms of infection, including fever and cultures
* Signs of C. difficile infection (diarrhea)
* Signs of hypersensitivity reactions
## Clinical Pearls
* The recommended duration of therapy is typically 7-14 days, but can be shorter or longer based on clinical assessment.
* Reconstitution and further dilution are required before IV infusion. Infusion should be over at least 30 minutes to reduce the risk of hypersensitivity reactions.
* Patients with cystic fibrosis may require higher doses and more frequent administration.
* In patients with severe renal impairment, the risk of neurotoxicity (e.g., seizures) is increased with piperacillin/tazobactam.
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**Disclaimer:** This information is intended for clinical pharmacy professionals and should not replace the official prescribing information or clinical judgment. Always verify current product information and guidelines before use.
