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# Piperacillin-Tazobactam
## Overview
Piperacillin-tazobactam is a combination of an extended-spectrum penicillin-class antibacterial agent and a beta-lactamase inhibitor.
## Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections (including diabetic foot infections)
* Community-acquired pneumonia
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
## Adult Dosing
* **Standard dose:** 3.375 grams (3 grams piperacillin / 0.375 grams tazobactam) intravenously every 6 hours.
* **Severe/nosocomial infections:** 4.5 grams (4 grams piperacillin / 0.5 grams tazobactam) intravenously every 6 or 8 hours.
* **Maximum daily dose:** Generally not to exceed 18 grams per day. Dosing frequency may be extended to every 8 hours for doses of 4.5 grams in certain severe infections, but this requires careful consideration of renal function and institutional guidelines.
## Pediatric Dosing
* **Intra-abdominal infections (3 months to 12 years):** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Hospital-acquired pneumonia (3 months to 12 years):** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **For doses greater than 50 kg equivalent weight:** Administer adult dose.
* **Higher doses (e.g., 300 mg piperacillin/3.75 mg tazobactam per kg per dose every 6 hours) may be used for severe infections, particularly in patients with cystic fibrosis or severe nosocomial infections, based on clinical judgment and institutional protocols.**
## Dose Adjustments
* **Renal Impairment (CrCl $\ge$ 40 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl 20-40 mL/min):** Administer the standard dose every 8 hours.
* **Renal Impairment (CrCl < 20 mL/min):** Administer the standard dose every 12 hours.
* **Hemodialysis:** Administer the standard dose every 12 hours and administer an additional dose of 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) after each dialysis session.
* **Hepatic Impairment:** No specific recommendations; use with caution.
## Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, pruritus, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), Stevens-Johnson syndrome, toxic epidermal necrolysis, interstitial nephritis, hematologic abnormalities (e.g., neutropenia, thrombocytopenia).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin and tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
* **Live bacterial vaccines:** May decrease efficacy.
## Monitoring
* Renal function (BUN, creatinine).
* Liver function tests (AST, ALT, bilirubin).
* Complete blood count (CBC), including platelet count.
* Electrolytes.
* Signs and symptoms of infection.
* For prolonged therapy: Monitor for *C. difficile*-associated diarrhea and signs of fungal superinfection.
## Clinical Pearls
* Dosing interval and route of administration are crucial for efficacy and safety, especially in patients with renal impairment.
* The combination is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
* Tazobactam inhibits many common beta-lactamases, extending the spectrum of piperacillin.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Monitor for signs of hypersensitivity reactions, especially in patients with a history of penicillin allergy.
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*This information is intended for healthcare professionals and does not replace comprehensive prescribing information. Always consult the most current prescribing information and professional resources for complete details before making any treatment decisions.*
