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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It is bactericidal and has broad-spectrum activity against many Gram-positive, Gram-negative, and anaerobic bacteria.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard Dose:** 3.375 grams every 6 hours or 4.5 grams every 8 hours administered IV.
* **Maximum Dose:** Not explicitly defined, but doses exceeding 4.5 grams every 6 hours are generally not recommended outside of specific critical care or infectious disease protocols.
## Pediatric Dosing
* **Children 0 to < 2 months:** Dosing is not well established and requires careful consideration by an infectious disease specialist. Dosing is typically based on piperacillin component weight-based dosing.
* **Children 2 months to < 12 years:** Dosing is typically based on the piperacillin component, ranging from 80-112.5 mg/kg/dose (piperacillin equivalent) every 6 or 8 hours, not to exceed the adult maximum dose. Specific guidance depends on the indication and severity of infection.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams every 6 hours or 3.375 grams every 8 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours or 3.375 grams every 12 hours.
* Dosing for hemodialysis patients should be adjusted based on the CrCl and administration during dialysis sessions.
## Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of immediate or severe allergic reaction to a beta-lactam antibiotic.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, elevated liver enzymes (AST, ALT).
* **Serious:** Hypersensitivity reactions (including anaphylaxis), Clostridioides difficile-associated diarrhea, seizures (especially with high doses or renal impairment), hematologic abnormalities (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** Can increase piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin; increased INR monitoring is recommended.
* **Methotrexate:** May decrease methotrexate levels; increased methotrexate monitoring is recommended.
## Monitoring
* Renal function (especially with dose adjustments).
* Liver function tests (periodic).
* Complete blood count (periodic, particularly with prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of C. difficile infection.
## Clinical Pearls
* The reconstitution volume of the diluent is critical and impacts the final concentration. Always confirm the concentration when preparing or administering.
* The duration of therapy should be guided by the clinical response and local susceptibility patterns.
* For febrile neutropenia, the duration is typically 7 days or until resolution of neutropenia and fever, whichever is longer.
* The piperacillin:tazobactam ratio is typically 8:1.
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**Disclaimer:** This information is intended for clinical use and does not substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols for definitive guidance.
