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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and 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
The typical dose is 3.375 g (piperacillin 3 g / tazobactam 0.375 g) or 4.5 g (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 to 8 hours. Duration of therapy is typically 7 to 14 days, depending on the indication and severity of infection. Dosing frequency and duration are often guided by local protocols and clinical response.
## Pediatric Dosing
Dosing varies by age and indication.
* **Patients 2 months and older:**
* Intra-abdominal infections: 100 mg piperacillin / 12.5 mg tazobactam per kg per dose administered every 8 hours.
* Nosocomial pneumonia: 100 mg piperacillin / 12.5 mg tazobactam per kg per dose administered every 6 hours.
* **Maximum dose:** 4.5 g per dose every 6 or 8 hours.
* Dosing for neonates and infants younger than 2 months is not well-established and requires careful consideration.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) IV every 8 hours.
* CrCl < 20 mL/min: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) IV every 8 hours.
* Hemodialysis: Administer 2.25 g (piperacillin 2 g / tazobactam 0.25 g) IV every 8 hours, plus an additional 0.75 g (piperacillin 0.67 g / tazobactam 0.08 g) dose after each dialysis session.
* **Hepatic Impairment:** No specific guidelines, but liver dysfunction may affect clearance.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
* History of immediate and severe allergic reaction to penicillin or cephalosporins.
## Adverse Effects
Common adverse effects include diarrhea, nausea, vomiting, rash, headache, insomnia, and eosinophilia. Serious adverse effects include hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures, and hematologic changes (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Vecuronium:** Piperacillin may prolong the neuromuscular blockade of vecuronium.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
* **Aminoglycosides:** Generally compatible, but administer separately due to potential for inactivation.
## Monitoring
* Renal function (baseline and periodically, especially in those with pre-existing renal impairment or receiving concurrent nephrotoxic agents).
* Liver function tests.
* Complete blood count (especially with prolonged therapy).
* Signs and symptoms of infection (clinical response).
* Electrolytes.
## Clinical Pearls
* Reconstituted solutions are stable for 24 hours at room temperature or 48 hours under refrigeration. Further dilution for IV infusion is also time-limited.
* Discontinue if hypersensitivity reaction occurs.
* Careful monitoring for signs of C. difficile infection is important, especially with prolonged therapy.
* Dosage adjustment for renal impairment is critical.
* Ensure adequate hydration to minimize the risk of crystalluria.
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**Disclaimer:** This information is intended for clinical pharmacy professionals and should not replace comprehensive prescribing information. Always verify current drug information with the product's official prescribing information and consult with a qualified healthcare provider before making any treatment decisions.
