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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination of an extended-spectrum penicillin-class antibacterial and 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 (empiric treatment)
## Adult Dosing
* **Complicated Intra-abdominal Infections, Complicated Skin/Skin-Structure Infections, Community-Acquired Pneumonia, Nosocomial Pneumonia:**
* Usual dose: 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously (IV) every 6 hours.
* Alternative dose: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours.
* **Febrile Neutropenia (Empiric):**
* Usual dose: 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 6 hours.
* Alternative dose: 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours.
*Maximum daily dose:* Generally not to exceed 18 grams (16g piperacillin/2g tazobactam) in a 24-hour period, depending on indication and renal function.
## Pediatric Dosing
* **Children < 12 years:** Dosing is highly variable based on indication and severity. Often based on piperacillin component. A common regimen for intra-abdominal infections is 90-100 mg piperacillin/11.25-12.5 mg tazobactam per kg per dose IV every 6-8 hours. Consult specific pediatric guidelines.
* **Children ≥ 12 years:** Dosed as adults.
## Dose Adjustments
* **Renal Impairment (CrCl ≥ 20 mL/min):** No dose adjustment necessary.
* **Renal Impairment (CrCl < 20 mL/min):**
* 3.375 gram dose: Administer 2.25 grams (2g piperacillin/0.25g tazobactam) IV every 8 hours.
* 4.5 gram dose: Administer 3.375 grams (3g piperacillin/0.375g tazobactam) IV every 8 hours.
* **Hemodialysis:** Dosing is complex and depends on the dose and frequency of dialysis. Typically, an additional dose is given after each dialysis session. Consult specific guidelines.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
## Adverse Effects
* Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, hypokalemia, elevated liver enzymes, positive Coombs test.
* Serious: Anaphylaxis, *Clostridioides difficile*-associated diarrhea, seizure activity (especially with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** May decrease methotrexate levels.
## Monitoring
* Renal function (especially with dose adjustments).
* Electrolytes (potassium).
* Liver function tests.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *Clostridioides difficile*-associated diarrhea.
## Clinical Pearls
* Reconstituted solutions are generally stable for 24 hours at room temperature or 48 hours when refrigerated.
* Infuse over at least 30 minutes. Longer infusion times (e.g., 4 hours) may be preferred for some indications or to achieve higher plasma concentrations.
* Consider local resistance patterns and institutional antibiograms when selecting empiric therapy.
* Beta-lactamase inhibitor component (tazobactam) expands the spectrum of activity to include many beta-lactamase producing organisms.
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*This information is intended for clinical decision support and does not replace the need to consult current official prescribing information and/or institutional protocols.*
