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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic (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
* Febrile neutropenia (empiric treatment)
## Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
Higher dose for severe infections or specific indications (e.g., nosocomial pneumonia, febrile neutropenia): 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 hours.
Maximum daily dose: 18 grams (16g piperacillin/2g tazobactam) intravenously per day, typically divided into 4 doses.
## Pediatric Dosing
Dosing is based on piperacillin component:
* Children 0 to 12 months: 80 to 100 mg/kg (piperacillin component) intravenously every 8 hours.
* Children > 12 months: 200 to 300 mg/kg (piperacillin component) intravenously every 6 hours.
* Maximum daily dose for children should not exceed the maximum adult daily dose.
* Dosing for febrile neutropenia in pediatric patients may follow specific institutional protocols.
## Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):** Reduce dose by 1/3 to 1/2. Frequency typically every 8 hours for standard dosing, or every 8-12 hours for higher dosing. Consider dialysis status.
* **Hepatic Impairment:** No dose adjustment is generally recommended, but caution is advised due to potential for impaired clearance.
## Contraindications
* History of hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics.
* History of immediate and severe allergic reaction to penicillin.
## Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, liver enzyme elevations.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis, hemolytic anemia.
## Key Drug Interactions
* **Probenecid:** May increase piperacillin/tazobactam serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (especially in prolonged therapy for neutropenia or thrombocytopenia).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
## Clinical Pearls
* Tazobactam protects piperacillin from degradation by many beta-lactamases, extending its spectrum of activity.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated.
* Avoid co-administration of piperacillin/tazobactam in the same IV line with amino glycosides due to potential inactivation. If co-administration is necessary, flush the line between infusions.
* Duration of therapy is typically guided by clinical response and may range from 5 to 14 days depending on the indication and severity of infection.
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*This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and institutional guidelines for complete details regarding dosing, administration, safety, and specific patient populations.*
