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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It provides broad-spectrum coverage, including *Pseudomonas aeruginosa*, streptococci, enteric gram-negative bacilli, and anaerobes.
## Primary Indications
* Moderate to severe infections caused by susceptible organisms:
* Hospital-acquired and ventilator-associated pneumonia.
* Complicated intra-abdominal infections.
* Complicated skin and skin structure infections.
* Gynecologic infections (postpartum endometritis).
* Febrile neutropenia (empiric therapy).
## Adult Dosing
* **Standard dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours.
* **Severe/Nosocomial infections:** 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 or 8 hours.
* **Extended/Continuous Infusion:** 4.5 g by prolonged infusion (e.g., over 4 hours) is frequently utilized in clinical practice for susceptible *Pseudomonas* to optimize time above MIC.
* **Maximum:** 18 g piperacillin per 24 hours.
## Pediatric Dosing
* **General infection (≥ 2 months):** 80 mg piperacillin/kg/dose every 6 or 8 hours.
* **Febrile neutropenia:** 80 mg piperacillin/kg/dose every 6 hours.
* **Maximum:** 4 g piperacillin (4.5 g total) per dose.
## Dose Adjustments
* **Renal Impairment:** Requires dose reduction based on creatinine clearance (CrCl). If CrCl < 40 mL/min, refer to specific renal adjustment tables (e.g., Sanford Guide or institutional protocols).
* **Hepatic Impairment:** No standard dosage adjustment required.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, or any component of the formulation.
* History of anaphylactic reactions to any beta-lactam (e.g., cephalosporins, carbapenems).
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (rash, anaphylaxis), seizures (related to high doses in renal failure), leukopenia/neutropenia (with prolonged use), and electrolyte disturbances (hypernatremia/hypokalemia).
## Key Drug Interactions
* **Methotrexate:** May increase methotrexate levels; monitor closely.
* **Aminoglycosides:** Piperacillin can inactivate aminoglycosides *in vitro* if mixed in the same IV line; administer at least 1 hour apart.
* **Warfarin/Anticoagulants:** May increase bleeding risk via platelet inhibition.
## Monitoring
* **Renal function:** Serum creatinine/BUN.
* **Hematology:** CBC with differential (if therapy > 2 weeks, monitor for neutropenia).
* **Clinical:** Observe for signs of hypersensitivity, superinfection, or diarrhea.
## Clinical Pearls
* **Sodium Load:** Each 4.5 g dose contains approximately 2.35 mEq (54 mg) of sodium; adjust for patients on sodium-restricted diets.
* **Empiric Selection:** Often considered a "broad-spectrum" workhorse; consider de-escalation once culture and susceptibility results are available to decrease pressure for resistance.
* **Local Policies:** Always consult your facility’s antibiogram and IV compatibility charts, as infusion times and renal cutoffs can vary by institutional policy.
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**Educational Disclaimer:** This information is for educational purposes only. Always consult the most current official prescribing information (package insert) and your institution’s clinical guidelines before prescribing or administering any medication.
