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# Piperacillin/Tazobactam
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor, 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
* Hospital-acquired pneumonia
* Febrile neutropenia (empiric treatment)
* Bacterial vaginosis (alternative)
## Adult Dosing
Standard dosing is **3.375 g (3 g piperacillin/0.375 g tazobactam) to 4.5 g (4 g piperacillin/0.5 g tazobactam) intravenously every 6 to 8 hours**.
* **Complicated intra-abdominal infections, hospital-acquired pneumonia, and febrile neutropenia:** typically 4.5 g IV every 6 hours.
* **Complicated skin and skin structure infections and community-acquired pneumonia:** typically 3.375 g IV every 6 to 8 hours.
* Maximum daily dose: 18 g (16 g piperacillin/2 g tazobactam).
## Pediatric Dosing
Dosing is weight-based and depends on indication and institutional protocol.
* **Children < 4 months:** Dosing varies significantly based on gestational and postnatal age; consult specialized resources.
* **Children ≥ 4 months to 12 years:** Dosing commonly ranges from **90 to 100 mg piperacillin per kg per dose** (total drug) IV every 6 to 8 hours. Maximum single dose is typically 4.5 g. Consider renal function.
## Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 20 mL/min: No dose adjustment needed.
* CrCl < 20 mL/min: Reduce dose frequency to every 8 hours and consider reducing the dose by one-third.
* Hemodialysis: Administer dose every 8 hours and give an additional 0.75 g dose after each dialysis session.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam therapy.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic abnormalities (neutropenia, thrombocytopenia, eosinophilia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Potential for increased anticoagulant effect; monitor INR.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* Signs and symptoms of infection.
* Renal function (serum creatinine, BUN).
* Liver function tests.
* Complete blood counts (especially with prolonged therapy).
* Signs of hypersensitivity or allergic reactions.
* INR if co-administered with warfarin.
* Methotrexate levels if co-administered.
## Clinical Pearls
* Reconstitute and dilute according to manufacturer instructions.
* Infuse over at least 30 minutes. Rapid infusion can cause hypersensitivity reactions.
* Monitor for signs of superinfection, especially with prolonged therapy.
* Dosing for pediatric patients, especially neonates, requires careful consideration of specific guidelines and renal function.
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**Disclaimer:** This information is intended for clinical use and does not replace comprehensive drug information resources. Always verify current prescribing information and consult institutional guidelines.
