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## Piperacillin/Tazobactam
### Overview
Piperacillin/tazobactam is a combination penicillin antibiotic and beta-lactamase inhibitor, effective against a broad spectrum of Gram-positive, Gram-negative, and anaerobic bacteria.
### Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Febrile neutropenia (as empiric therapy)
### Adult Dosing
* **Standard Dosing:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously every 6 hours.
* **Higher Dosing (e.g., severe infections, nosocomial pneumonia, febrile neutropenia):** 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 or 8 hours.
* Maximum daily dose: 18 grams (piperacillin 16 g / tazobactam 2 g).
* **Duration:** Typically 7-14 days, depending on the infection and patient response.
### Pediatric Dosing
* **Children < 2 months:** Dosing is highly variable and depends on gestational and postnatal age. Consult specialized pediatric infectious disease resources.
* **Children ≥ 2 months:**
* **Body weight < 40 kg:** 100 mg piperacillin / 12.5 mg tazobactam per kg per dose intravenously every 6 hours.
* **Body weight ≥ 40 kg:** Use adult dosing (3.375 g or 4.5 g IV every 6 or 8 hours).
* Maximum dose: 4.5 grams per dose.
### Dose Adjustments
* **Renal Impairment (CrCl < 20 mL/min):**
* Standard dosing (3.375 g q6h): 2.25 grams (piperacillin 2 g / tazobactam 0.25 g) intravenously every 8 hours.
* Higher dosing (4.5 g q6-8h): 2.25 grams (piperacillin 2 g / tazobactam 0.25 g) intravenously every 12 hours.
* **Hemodialysis:** Administer usual dose, followed by an additional 0.75 g dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically recommended.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, elevated liver enzymes.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, interstitial nephritis.
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** May decrease the efficacy of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance, leading to increased methotrexate toxicity. Monitor methotrexate levels.
### Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT, bilirubin)
* Complete blood count (CBC) with differential, especially during prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* INR if co-administered with warfarin.
* Methotrexate levels if co-administered with methotrexate.
### Clinical Pearls
* Administer by slow intravenous infusion over at least 30 minutes.
* Reconstituted solutions should be used within 24 hours when refrigerated or within 12 hours at room temperature.
* Tazobactam protects piperacillin from degradation by beta-lactamase enzymes.
* Empiric use in febrile neutropenia should cover *Pseudomonas aeruginosa*.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making treatment decisions.*
