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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is bactericidal and acts by inhibiting bacterial cell wall synthesis.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Bacterial infections in febrile neutropenic patients
* Other serious infections caused by susceptible organisms
## Adult Dosing
The typical dose is 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) or 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) administered intravenously every 6 to 8 hours.
* **Maximum dose:** Generally, 18 grams per day (divided into doses, usually every 4 to 6 hours). Specific maximums can vary based on indication and renal function.
## Pediatric Dosing
Dosing is based on piperacillin weight. Tazobactam is dosed proportionally.
* **Patients ≥ 2 months:**
* 3.375 grams IV every 6 hours (pediatric dose for intra-abdominal infection)
* 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours (for other infections)
* **Maximum dose:** 18.75 mg piperacillin/1.4 mg tazobactam per kg per dose.
* **Note:** For children weighing > 40 kg, use the adult dose. Local protocols may differ.
## Dose Adjustments
Dose reduction and/or increased dosing interval is necessary in patients with renal impairment.
* **CrCl 20-40 mL/min:** Reduce dose by 25% (e.g., 2.25 g or 3.375 g q6-8h).
* **CrCl < 20 mL/min:** Reduce dose by 50% (e.g., 2.25 g q8h or 3.375 g q12h).
* **Hemodialysis:** Administer dose at the end of dialysis and supplement with an additional dose of 0.75 g. Dosing frequency is usually every 8 hours.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactam antibiotics.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antimicrobial.
## Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever.
Serious: Anaphylaxis, *Clostridioides difficile*-associated diarrhea, seizures, neutropenia, thrombocytopenia, prolonged prothrombin time, liver enzyme elevations.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Warfarin:** Piperacillin may decrease warfarin's effect; monitor INR closely.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of these agents.
* **Methotrexate:** Piperacillin may decrease methotrexate levels; monitor methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests.
* Complete blood count (CBC), including platelets.
* Signs and symptoms of infection.
* Signs and symptoms of hypersensitivity reactions.
* INR if co-administered with warfarin.
* *Clostridioides difficile* testing if diarrhea develops.
## Clinical Pearls
* Administer intravenously only. Do not administer intramuscularly.
* Infusion time is typically 30 minutes. Rapid infusion can increase the risk of seizures.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Tazobactam inhibits beta-lactamases, extending the spectrum of piperacillin to cover many beta-lactamase producing organisms.
* Adjust dose based on severity of illness and renal function.
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_Disclaimer: This information is intended for clinical professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information, institutional protocols, and clinical guidelines before making any treatment decisions._
