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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic consisting of an extended-spectrum ureidopenicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It provides bactericidal activity against many Gram-positive, Gram-negative, and anaerobic organisms.
## Primary Indications
* Intra-abdominal infections (e.g., peritonitis, appendicitis)
* Nosocomial and ventilator-associated pneumonia
* Skin and skin structure infections
* Empiric therapy for febrile neutropenia
* Bacteremia and sepsis
## Adult Dosing
* **Standard dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* **Severe infections:** 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6–8 hours.
* **Extended/Continuous Infusion:** 4.5 g IV infused over 4 hours every 8 hours is often utilized to optimize pharmacodynamics against resistant organisms (refer to institutional protocol).
* **Maximum:** 18 g (piperacillin component) per 24 hours.
## Pediatric Dosing
* **Neonates (≤ 7 days):** 80 mg/kg/day (piperacillin component) divided every 12 hours.
* **Neonates (> 7 days) and Infants (< 9 months):** 240–300 mg/kg/day divided every 6–8 hours.
* **Children (9 months to 12 years):** 240–300 mg/kg/day divided every 6 hours. Maximum of 16 g piperacillin/day.
* *Note: Always verify pediatric dosing against weight-based institutional and neonatal ICU guidelines.*
## Dose Adjustments
* **Renal Impairment (CrCl < 40 mL/min):** Requires dose reduction and/or interval extension.
* **Hemodialysis:** Supplementation is usually required post-dialysis due to drug removal.
* **Hepatic Impairment:** No dosage adjustment needed.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, or any component of the formulation.
* History of severe allergic reactions (e.g., anaphylaxis, Stevens-Johnson syndrome) to any beta-lactam antibiotic (due to potential cross-reactivity).
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (rash, anaphylaxis), neutropenia/thrombocytopenia (usually with prolonged use), seizure (with high doses in renal failure).
## Key Drug Interactions
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro*; do not mix in the same IV line. Administer at least 1 hour apart.
* **Methotrexate:** May increase serum levels and toxicity of methotrexate.
* **Warfarin:** May enhance the anticoagulant effect by altering gut flora; monitor INR closely.
* **Probenecid:** Increases serum concentrations of piperacillin.
## Monitoring
* **Renal Function:** Monitor serum creatinine and adjust dose accordingly.
* **Hematologic:** Monitor CBC (platelets/neutrophils) periodically, especially in patients receiving therapy >10 days.
* **Clinical:** Monitor for signs of therapeutic response and allergic reaction.
* **Electrolytes:** Each gram of piperacillin contains ~2.8 mEq (64 mg) of sodium; monitor in fluid-restricted or sodium-sensitive patients.
## Clinical Pearls
* **Spectrum:** Does not cover MRSA, *Acinetobacter* (highly variable), carbapenem-resistant Enterobacteriaceae (CRE), or atypical pathogens like *Legionella*.
* **Stability:** Once reconstituted, stability varies; store according to manufacturer/institutional guidelines.
* **Transition:** Consider de-escalation based on culture and sensitivity data to prevent emergence of resistance.
* **Standardize:** Rapid infusion (30 min) is common, but extended infusion (4 hours) is preferred for serious infections to maximize the time the free drug concentration remains above the MIC (fT > MIC).
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**Disclaimer:** This information is intended for educational purposes for healthcare professionals. Dosing, stability, and compatibility may vary by institutional protocol and local antibiotic resistance patterns. Always verify individual patient requirements and current clinical guidelines via the official electronic package insert or a verified clinical decision-support resource (e.g., Lexicomp, UpToDate) before prescribing.
