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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is bactericidal and active against many Gram-positive, Gram-negative, and anaerobic bacteria.
### Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin-structure infections
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (in combination with an aminoglycoside)
### Adult Dosing
* **Standard Dose:** 3.375 g every 6 hours or 4.5 g every 6 or 8 hours intravenously (IV).
* **Maximum Dose:** 4.5 g every 6 hours IV.
* Dosing frequency and duration depend on the severity of infection and clinical response. For critically ill patients or those with resistant pathogens, higher doses (e.g., 4.5 g every 4 hours) or extended infusions (e.g., 4-hour infusion) may be considered, but specific protocols should be followed.
### Pediatric Dosing
* **Neonates and Infants < 12 months:** Dosing is complex and based on gestational and postnatal age. Consult specific pediatric guidelines. A common starting point for post-meningitis is 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours for premature infants and 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 6 hours for term infants.
* **Children ≥ 12 months:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose every 8 hours IV.
* **Maximum Pediatric Dose:** Generally, do not exceed the adult dose of 4.5 g every 6 hours.
### Dose Adjustments
* **Renal Impairment:**
* CrCl ≥ 40 mL/min: No adjustment needed.
* CrCl 20-39 mL/min: 2.25 g every 6 hours or 3.375 g every 8 hours.
* CrCl < 20 mL/min: 2.25 g every 8 hours.
* Hemodialysis: 2.25 g every 8 hours, with an additional 0.75 g dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is typically recommended, but monitor closely.
### Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
* History of cholestatic jaundice or hepatic dysfunction associated with prior piperacillin/tazobactam use.
### Adverse Effects
* Diarrhea (most common)
* Nausea, vomiting
* Rash, pruritus
* Headache
* Insomnia
* Fever, injection site reactions
* **Serious:** Hypersensitivity reactions (anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizure, hepatic dysfunction, neutropenia, thrombocytopenia.
### Key Drug Interactions
* **Aminoglycosides:** May have synergistic activity, but can also lead to inactivation of piperacillin/tazobactam. Avoid co-administration in vitro. Separate administration if used concurrently.
* **Probenecid:** Increases and prolongs piperacillin/tazobactam serum concentrations.
* **Warfarin:** Piperacillin may decrease warfarin's effect; monitor INR closely.
* **Neuromuscular blocking agents:** Piperacillin may prolong the action of vecuronium.
### Monitoring
* Renal function (baseline and periodically during therapy)
* Liver function tests (baseline and periodically)
* Complete blood count (especially for prolonged therapy)
* Signs and symptoms of infection and hypersensitivity reactions
* INR if patient is on warfarin
### Clinical Pearls
* Piperacillin/tazobactam is often reconstituted and then further diluted for IV infusion. Follow manufacturer guidelines for preparation and administration.
* Extended infusions (e.g., 4 hours) may improve efficacy in critically ill patients by maintaining higher drug concentrations.
* Discontinue if hypersensitivity reaction occurs.
* Consider the emergence of resistance, particularly in prolonged treatment courses.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the current prescribing information and institutional guidelines for complete details and to ensure patient safety.
