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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination containing a broad-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). It provides coverage against Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms.
## Primary Indications
* Moderate to severe infections caused by susceptible organisms: intra-abdominal, skin/skin structure, pneumonia (nosocomial/CAP), gynecologic, and complicated urinary tract infections.
* Empiric therapy for febrile neutropenia.
## 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.
* **Administration:** Typically infused over 4 hours (extended infusion) to optimize pharmacodynamics in critically ill patients, though 30-minute intermittent infusions remain common.
## Pediatric Dosing
* **Neonates (0–1 month):** Dosing is highly age/weight-dependent; usually 75–150 mg/kg/day divided every 8–12 hours.
* **Infants/Children (≥1 month):** 80–100 mg/kg/day (based on piperacillin component) divided every 6–8 hours.
* **Maximum dose:** Should not exceed 16 g piperacillin/day in children.
## Dose Adjustments
* **Renal Impairment:** Requires dose reduction or extended intervals based on creatinine clearance (CrCl).
* CrCl 20–40 mL/min: 2.25 g q6h or 3.375 g q8h.
* CrCl <20 mL/min: 2.25 g q8h.
* **Hemodialysis:** Supplementation is required post-dialysis (often 0.75 g post-HD).
* **Hepatic Impairment:** No standard adjustment needed, though monitor closely.
## Contraindications
* History of severe hypersensitivity (anaphylaxis) to any beta-lactam (penicillins, cephalosporins, carbapenems).
* Known hypersensitivity to tazobactam.
## Adverse Effects
* **Common:** Diarrhea, constipation, nausea, headache, injection site reactions.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis, DRESS), leukopenia/neutropenia (with prolonged use), hepatotoxicity, and seizure (usually with high doses in renal impairment).
## Key Drug Interactions
* **Aminoglycosides:** May result in inactivation if mixed in the same IV line; administer at least 1 hour apart.
* **Probenecid:** Increases serum concentrations of piperacillin/tazobactam by inhibiting renal tubular secretion.
* **Methotrexate:** Penicillins may decrease renal clearance, increasing risk of toxicity.
* **Warfarin:** Theoretical risk of elevated INR due to alteration of gut flora or drug interactions.
## Monitoring
* Renal function (BUN/SCr).
* Complete blood count (monitor for cytopenias during extended therapy >14 days).
* Baseline and periodic LFTs.
* Monitor for signs of hypersensitivity and *C. difficile* diarrhea.
## Clinical Pearls
* **Pseudomonal Coverage:** Piperacillin-tazobactam is a primary agent for empiric *Pseudomonas* coverage.
* **Stability:** Once reconstituted, stability varies; check facility-specific IV compatibility charts, especially regarding Y-site administration with other medications.
* **Sodium Load:** Each 4.5 g dose contains approximately 12.3 mEq (282 mg) of sodium; consider in patients on strict sodium restriction.
* **Culture Directed:** De-escalate therapy based on susceptibility reports to minimize resistance (e.g., "bacterial pressure").
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**Disclaimer:** This information is for educational purposes only. Drug dosing, contraindications, and interaction profiles can change. Always verify current prescribing information using institutional protocols, the package insert, or professional pharmacy resources (e.g., Lexicomp, Micromedex) before prescribing or administering medication.
