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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many 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 (in combination with an aminoglycoside)
## Adult Dosing
* **General Dosing:** 3.375 grams (piperacillin 3 g/tazobactam 0.375 g) intravenously every 6 hours or 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 8 hours.
* **Dosing for severe infections or infections due to less susceptible organisms:** 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 6 hours.
* **Dosing for febrile neutropenia:** Typically 4.5 grams (piperacillin 4 g/tazobactam 0.5 g) intravenously every 6 hours, often in combination with an aminoglycoside.
* **Maximum dose:** Generally does not exceed 18 grams per day (e.g., 4.5 grams every 6 hours).
* **Infusion:** Administer over a minimum of 30 minutes.
## Pediatric Dosing
* **Children < 12 years of age:** Dosing is not well-established. Refer to institutional guidelines or specialized pediatric infectious disease resources. Dosing is typically based on piperacillin component.
* **Children ≥ 12 years of age:** Dosing is generally the same as adults.
* **Infants < 2 months of age:** Dosing is not well-established.
## Dose Adjustments
* **Renal Impairment (CrCl ≥ 20 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl < 20 mL/min):**
* For 3.375 g every 6 hours dosing: Administer 2.25 g every 6 hours.
* For 4.5 g every 8 hours dosing: Administer 3.375 g every 8 hours.
* For 4.5 g every 6 hours dosing: Administer 2.25 g every 6 hours.
* **Hemodialysis:** Administer the usual recommended dose of piperacillin/tazobactam and supplement with an additional dose of 2.25 g after each dialysis period.
* **Hepatic Impairment:** No specific dose adjustment is recommended.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of a severe allergic reaction (e.g., anaphylaxis) to these agents.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin can prolong the neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially if CrCl < 20 mL/min or patient is on hemodialysis).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
* Complete blood count (CBC) with differential and platelet count (especially with prolonged therapy).
* Liver function tests (LFTs).
* Clinical signs of infection and appropriate culture and sensitivity results.
## Clinical Pearls
* Piperacillin/tazobactam has broad-spectrum activity, making it a common choice for empiric therapy of serious infections.
* Dosing frequency and amount can be adjusted based on the severity of illness, the infecting organism, and the patient's renal function.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours at room temperature.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing organisms.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the current prescribing information and relevant clinical guidelines before making any treatment decisions.
