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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active 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 (including ventilator-associated pneumonia)
* Febrile neutropenia (empiric treatment)
### Adult Dosing
Standard dose: 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV).
Alternative dose: 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV, depending on indication and institutional protocol.
Maximum dose: Typically 4.5 grams every 6 hours. Higher doses may be used in severe infections, particularly those caused by *Pseudomonas aeruginosa*.
### Pediatric Dosing
* **3 months to < 12 years:** Dosing is based on piperacillin weight.
* Complicated intra-abdominal infections: 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours IV.
* Hospital-acquired pneumonia: 75 mg piperacillin/9.375 mg tazobactam per kg per dose every 6 hours IV.
* **≥ 12 years:** Dosing typically follows adult guidelines (e.g., 3.375g or 4.5g every 6 or 8 hours IV).
Dosing in neonates and infants < 3 months is not well established and should be guided by specialist consultation.
### Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No dose adjustment needed.
* CrCl 20-40 mL/min: Reduce frequency to every 8 hours.
* CrCl < 20 mL/min: Reduce frequency to every 12 hours.
* For doses of 3.375g, administer 2.25g every 8 hours if CrCl is 20-40 mL/min, and 2.25g every 12 hours if CrCl is < 20 mL/min.
* For doses of 4.5g, administer 3.375g every 8 hours if CrCl is 20-40 mL/min, and 3.375g every 12 hours if CrCl is < 20 mL/min.
* Hemodialysis: Administer standard dose every 12 hours, with an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment, but monitor closely.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam use.
### Adverse Effects
Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, eosinophilia, elevated liver enzymes.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures, neutropenia, thrombocytopenia, interstitial nephritis, prolonged PR interval, bleeding abnormalities.
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin serum concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin can prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may reduce methotrexate clearance; monitor methotrexate levels.
* **Live Vaccines:** May decrease antibody response.
### Monitoring
* Renal function (baseline and during therapy, especially with dose adjustments).
* Liver function tests (baseline and periodically).
* Complete blood count (periodic, especially for prolonged therapy).
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile* infection.
* INR if co-administered with warfarin.
### Clinical Pearls
* Reconstituted solutions should be used within 24 hours if refrigerated or within 1 hour if at room temperature, unless otherwise specified by the manufacturer or institutional policy.
* Infuse over at least 30 minutes for doses up to 2.25g (2g/0.25g) or 30-45 minutes for larger doses to minimize infusion reactions.
* Consider de-escalation once culture and sensitivity results are available.
* Tazobactam broadens the spectrum of piperacillin by inhibiting many beta-lactamases.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines for complete and up-to-date details. Local protocols may vary.*
