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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. It is bactericidal and effective 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
* Empirical treatment of febrile neutropenia
## Adult Dosing
* **Standard Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously (IV) every 6 hours.
* **Severe/Nosocomial Infections:** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) IV every 6 or 8 hours. Dosing frequency depends on local protocol and severity of infection.
* **Maximum Daily Dose:** Typically 18 grams (piperacillin 16 g / tazobactam 2 g) per day.
## Pediatric Dosing
Dosing is weight-based and depends on the indication and severity of infection. Specific dosing should be guided by local protocols or pediatric infectious disease recommendations. Examples include:
* **3 months and older:** Typically 2.5 to 3.375 grams (piperacillin 2 g / tazobactam 0.25 g to piperacillin 3 g / tazobactam 0.375 g) per 100 mL of fluid administered over 30 minutes every 6 or 8 hours.
* **Severe infections or febrile neutropenia:** May require higher doses up to 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) every 6 or 8 hours.
## Dose Adjustments
* **Renal Impairment:** Dose reduction or increased interval is necessary for creatinine clearance (CrCl) < 40 mL/min. Consult prescribing information for specific adjustments based on CrCl. Hemodialysis patients generally require an additional dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or any component of the formulation.
* History of severe allergic reaction (e.g., anaphylaxis) to beta-lactams.
## Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Headache
* Rash, pruritus
* Increased liver enzymes (AST, ALT)
* Superinfection (e.g., C. difficile-associated diarrhea)
* Hypersensitivity reactions, including anaphylaxis
## Key Drug Interactions
* **Probenecid:** May increase piperacillin-tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong neuromuscular blockade.
* **Warfarin:** May decrease warfarin's anticoagulant effect. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
## Monitoring
* Renal function (especially in patients with impaired renal function or receiving concomitant nephrotoxic agents)
* Liver function tests
* Signs and symptoms of superinfection
* Clotting parameters if on warfarin
* Methotrexate levels if co-administered
## Clinical Pearls
* Tazobactam extends the spectrum of piperacillin to include many beta-lactamase-producing bacteria.
* Administer over at least 30 minutes. Avoid rapid IV infusion.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated.
* Sodium content: Each gram of piperacillin contains approximately 1.12 mEq of sodium, and each 0.125 g of tazobactam contains approximately 0.07 mEq of sodium. Consider total sodium load in fluid-restricted patients.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and professional guidelines for complete and up-to-date information before making treatment decisions.
