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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is a combination penicillin-class antibacterial and a beta-lactamase inhibitor. It is active against a broad spectrum of gram-positive and gram-negative bacteria, including many anaerobes.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 grams piperacillin / 0.375 grams tazobactam) intravenously every 6 hours.
* **Maximum Dose:** Typically 4.5 grams (4 grams piperacillin / 0.5 grams tazobactam) intravenously every 6 or 8 hours, depending on indication and local guidelines. Higher doses may be used for severe infections, particularly hospital-acquired pneumonia.
* **Duration of Therapy:** Varies based on indication, severity of infection, and clinical response, typically 4-14 days.
## Pediatric Dosing
* **Children < 2 months:** Dosing is not established and should be based on institutional protocols, considering gestational and postnatal age.
* **Children ≥ 2 months:**
* **Dosing based on piperacillin component:** 80 mg/kg/dose (piperacillin) every 6 or 8 hours. Tazobactam is dosed proportionally (10 mg/kg/dose).
* **Maximum Pediatric Dose:** Typically capped at the adult dose of 4.5 grams every 6 or 8 hours.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Administer 2.25 grams (2 grams piperacillin / 0.25 grams tazobactam) intravenously every 6 hours.
* CrCl < 20 mL/min: Administer 2.25 grams intravenously every 8 hours.
* For doses given every 8 hours, consider administering 4.5 grams (4g piperacillin/0.5g tazobactam) every 12 hours.
* Hemodialysis: Administer 2.25 grams every 8 hours, with an additional 0.75 grams dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or any component of the formulation.
* History of an allergic reaction (anaphylaxis) to beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, injection site reactions, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (neutropenia, thrombocytopenia, leukopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Aminoglycosides:** Synergistic activity against some organisms, but can be physically incompatible. Avoid co-administration in the same IV line.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of rocuronium and vecuronium.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* **Renal function:** Essential for dose adjustments.
* **Liver function tests:** Monitor periodically.
* **Hematologic parameters:** Monitor complete blood count, especially with prolonged therapy.
* **Signs of *C. difficile* infection:** Diarrhea.
* **Signs of hypersensitivity reactions:** Rash, fever, pruritus, anaphylaxis.
* **Clinical response:** Assess for improvement in signs and symptoms of infection.
## Clinical Pearls
* Piperacillin/tazobactam is typically administered by IV infusion over 30 minutes.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* It is important to rule out hypersensitivity to other penicillins or cephalosporins prior to administration.
* Dosing for severe infections, such as hospital-acquired pneumonia, may involve higher doses and/or extended infusion times (e.g., 4-hour infusions) per institutional guidelines. Uncertainty exists regarding optimal dosing in critically ill patients, and consideration of pharmacokinetic/pharmacodynamic principles is advised.
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*Please verify current prescribing information for the most up-to-date and complete details.*
