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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin and 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
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
### Adult Dosing
* **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) IV every 6 or 8 hours.
* **Dosing Frequency:** Typically every 6 hours for most indications. For febrile neutropenia, may be given every 8 hours.
* **Duration:** Varies by indication and clinical response.
* **Continuous Infusion:** For critically ill patients or those with severe infections, continuous infusion of 3.375g or 4.5g over 24 hours may be considered. Reconstitution and dilution must follow manufacturer guidelines.
### Pediatric Dosing
* **Patients < 12 years of age:** 100 mg piperacillin per kg of body weight per dose, administered every 8 hours. Total daily dose should not exceed 16 grams of piperacillin.
* **Patients ≥ 12 years of age:** Same as adult dosing.
* **Neonates and Infants < 2 months of age:** Dosing is complex and should be based on gestational and postnatal age. Refer to specific pediatric guidelines.
### Dose Adjustments
* **Renal Impairment (CrCl > 20 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl ≤ 20 mL/min):**
* 3.375g dose: Administer 2.25g every 6 or 8 hours.
* 4.5g dose: Administer 3.375g every 6 or 8 hours.
* **Hemodialysis:** Administer the post-hemodialysis dose and an additional supplemental dose of 0.75g to 2.25g depending on the initial piperacillin dose. Dosing should occur after each dialysis session.
* **Hepatic Impairment:** No dose adjustment recommended.
### Contraindications
* Known serious hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
### Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia.
* **Serious:** Hypersensitivity reactions (anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (especially with high doses or renal impairment), hematologic abnormalities (neutropenia, thrombocytopenia), interstitial nephritis, hepatotoxicity.
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin plasma concentrations.
* **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the efficacy of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
### Monitoring
* **Renal function:** Essential for dose adjustment.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** Monitor for hematologic changes, especially with prolonged therapy.
* **Electrolytes:** Especially if fluid overload or electrolyte imbalances are a concern.
* **Signs of hypersensitivity and *C. difficile* infection.**
### Clinical Pearls
* Reconstitute with sterile water for injection or sodium chloride 0.9% for injection. Further dilute to the appropriate volume with compatible IV fluid (e.g., NaCl 0.9%, D5W) for infusion.
* Administer IV over at least 30 minutes. For continuous infusion, follow specific guidelines for preparation and infusion rate.
* Monitor for signs of hypersensitivity, particularly in patients with a history of penicillin allergy.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of activity against beta-lactamase producing organisms.
**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines for definitive patient care decisions.
