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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin-class beta-lactam antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by many bacterial beta-lactamase enzymes, extending its spectrum of activity to include many gram-negative bacteria that are otherwise resistant to piperacillin alone.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Nosocomial infections caused by piperacillin-resistant, beta-lactamase producing *Enterobacteriaceae*
## Adult Dosing
Standard adult dosing is typically **3.375 grams (3 grams piperacillin / 0.375 grams tazobactam)** or **4.5 grams (4 grams piperacillin / 0.5 grams tazobactam)** administered intravenously every 6 to 8 hours. The specific dose and frequency depend on the severity and type of infection and local institutional protocols. The maximum daily dose should not exceed 18 grams (16 grams piperacillin / 2 grams tazobactam).
## Pediatric Dosing
Dosing is based on the piperacillin component.
* **Children 2 months of age and older:** Dosing ranges from **75 mg/kg/day to 100 mg/kg/day of piperacillin**, divided into 3 or 4 doses, not to exceed 4.5 grams per dose or 18 grams per day. The tazobactam dose is typically 1/8th of the piperacillin dose.
* **Infants younger than 2 months:** Dosing is less well-established and requires careful consideration of gestational and postnatal age, as well as renal function. Consult specific pediatric guidelines or institutional protocols.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) or 3.375 grams (3g piperacillin/0.375g tazobactam) every 8 hours.
* CrCl < 20 mL/min: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours or 3.375 grams (3g piperacillin/0.375g tazobactam) every 12 hours.
* Hemodialysis: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours, with an additional dose of 0.75 grams (0.675g piperacillin/0.075g tazobactam) after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is generally required.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactams.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and phlebitis at the injection site. Serious adverse effects can include hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, neutropenia, thrombocytopenia, and seizure activity (more common with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the duration of neuromuscular blockade.
* **Warfarin:** May decrease the effectiveness of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity. Monitor methotrexate levels.
## Monitoring
* Renal function (baseline and periodically during treatment, especially in patients with pre-existing renal impairment or those receiving concomitant nephrotoxic agents).
* Liver function (baseline and periodically).
* Complete blood count (CBC), including platelet count, especially with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Prothrombin time/INR if co-administered with warfarin.
## Clinical Pearls
* Piperacillin/tazobactam is a potent antibiotic often reserved for moderate to severe infections or those caused by resistant organisms due to its broad spectrum.
* Reconstitution and dilution guidelines must be strictly followed to ensure appropriate concentration and prevent precipitation.
* Due to its high sodium content, consider in patients on sodium-restricted diets.
* The decision to use piperacillin/tazobactam should be guided by local antibiograms and susceptibility testing, when available.
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**Disclaimer:** This information is intended for clinical pharmacy professionals and does not replace comprehensive prescribing information. Always consult the official prescribing information and institutional guidelines for the most current and complete details.
