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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic and beta-lactamase inhibitor.
### Primary Indications
* Complicated intra-abdominal infections (cIAI)
* Complicated skin and skin structure infections (cSSSI)
* Community-acquired pneumonia (CAP)
* Nosocomial pneumonia (hospital-acquired pneumonia, HAP)
### Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) intravenously every 6 hours.
* **High-Dose Dosing:** 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours for severe infections, hospital-acquired pneumonia, or infections due to *Pseudomonas aeruginosa*.
* **Maximum Dose:** No explicit maximum dose stated, but typically not to exceed 18 grams daily (16g piperacillin/2g tazobactam) in divided doses.
### Pediatric Dosing
* **Children < 6 months:** Dosing is not well-established and should be based on institutional protocols, considering severity of infection and patient factors.
* **Children ≥ 6 months:**
* **cIAI:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **cSSSI:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose intravenously every 6 hours.
* **CAP:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose intravenously every 6 hours.
* **Maximum Dose in Pediatrics:** Do not exceed adult doses.
### Dose Adjustments
* **Renal Impairment (CrCl ≥ 50 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl 20-40 mL/min):** Administer the recommended dose every 8 hours.
* **Renal Impairment (CrCl < 20 mL/min):** Administer half the recommended dose every 8 hours.
* **Hemodialysis:** Administer the recommended dose every 8 hours and supplement with an additional one-third of the dose after each dialysis session.
* **Hepatic Impairment:** No dose adjustment generally required, but caution is advised.
### Contraindications
* Known severe hypersensitivity to piperacillin, tazobactam, other beta-lactam antibiotics, or any component of the formulation.
### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, pruritus, fever, eosinophilia, elevated liver enzymes (AST, ALT).
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with renal impairment or high doses), hematologic effects (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; monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase toxicity.
* **Tetracyclines, Chloramphenicol:** Potential antagonism.
### Monitoring
* Renal function (baseline and periodically).
* Liver function tests (baseline and periodically).
* Complete blood count (especially if prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
* Clinical response to therapy.
### Clinical Pearls
* Piperacillin/tazobactam has a broad spectrum of activity, including many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic bacteria.
* Tazobactam protects piperacillin from degradation by many beta-lactamases.
* Infusion-related reactions (e.g., phlebitis) can occur; consider slow infusion or central line.
* Reconstituted solutions should be used within 24 hours if refrigerated or within 12 hours at room temperature, depending on the diluent.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for definitive dosing and management.*
