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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination antibiotic consisting of a broad-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). 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 Dose:** 3.375 grams (piperacillin 3 g / tazobactam 0.375 g) intravenously every 6 hours or 4.5 grams (piperacillin 4 g / tazobactam 0.5 g) intravenously every 8 hours.
* **Higher Doses for Severe Infections or specific pathogens:** May be used up to 4.5 grams IV every 4 hours or 225 mg/kg/day (piperacillin component) divided into 4 doses, not to exceed 18 g/day (piperacillin component). Specific indications and dosing are often guided by institutional antibiograms and clinical judgment.
### Pediatric Dosing
* **For patients 2 months of age and older:** Dosing is typically based on the piperacillin component.
* **3.0 g/0.375 g piperacillin/tazobactam IV every 6 hours:** 100 mg/kg/dose (piperacillin component) every 6 hours. Maximum dose of 4 g piperacillin per dose.
* **4.5 g/0.5 g piperacillin/tazobactam IV every 8 hours:** 100 mg/kg/dose (piperacillin component) every 8 hours. Maximum dose of 4 g piperacillin per dose.
* **Neonates and infants younger than 2 months:** Dosing is complex and based on gestational and postnatal age, often requiring specialized pediatric infectious disease consultation.
### Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 g (piperacillin 2 g / tazobactam 0.25 g) IV every 6 hours or 3.375 g (piperacillin 3 g / tazobactam 0.375 g) IV every 8 hours.
* CrCl < 20 mL/min: 2.25 g (piperacillin 2 g / tazobactam 0.25 g) IV every 8 hours.
* Hemodialysis: Administer dose after dialysis and adjust as for CrCl < 20 mL/min. An additional 0.75 g dose should be administered after each dialysis session.
* **Hepatic Impairment:** No dose adjustment is typically required.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactam antibiotics.
* History of immediate or severe allergic reaction to these drugs.
### Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, constipation, abdominal pain.
* **Serious:**
* Hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome, DRESS)
* *Clostridioides difficile*-associated diarrhea
* Seizures (especially with renal impairment and high doses)
* Hematologic effects (thrombocytopenia, neutropenia, eosinophilia, prolonged bleeding time)
* Hepatotoxicity
* Acute kidney injury
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations.
* **Neuromuscular blocking agents:** Piperacillin may prolong the effect of vecuronium.
* **Warfarin:** May decrease the effect of warfarin. Monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels.
### Monitoring
* Renal function (baseline and periodically during therapy)
* Liver function tests (baseline and periodically)
* Complete blood count (especially for prolonged therapy or high doses)
* Signs and symptoms of hypersensitivity reactions
* Signs and symptoms of *C. difficile* infection
* Clinical response to therapy (fever, white blood cell count, site of infection)
### Clinical Pearls
* Piperacillin/tazobactam is often reconstituted with sterile water and then further diluted in an appropriate IV fluid (e.g., 0.9% NaCl, D5W). Consult manufacturer's instructions for preparation and administration.
* For febrile neutropenia, consider patient-specific risk factors, local resistance patterns, and severity of illness when selecting empiric therapy.
* Discontinue therapy immediately if signs of hypersensitivity or severe rash occur.
* Tazobactam does not have significant antibacterial activity on its own but protects piperacillin from degradation by many beta-lactamases.
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*Disclaimer: This information is intended for clinical professionals and does not replace complete prescribing information. Always consult the current official prescribing information and institutional guidelines before administering any medication.*
