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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination penicillin-class antibiotic with a beta-lactamase inhibitor. It has broad-spectrum activity 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) intravenously every 6 hours.
High dose: 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. Higher doses may be used for severe infections or those caused by less susceptible organisms, though specific institutional protocols often guide this.
### Pediatric Dosing
Dosing varies by indication and patient weight. Generally, for patients 3 months and older:
* **Complicated Intra-abdominal Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Hospital-acquired Pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Febrile Neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* Maximum single dose: 4.5 grams.
* Maximum daily dose: 18 grams.
* Dosing should be adjusted for renal impairment. For neonates and infants under 3 months, specific dosing recommendations are less established and often guided by institutional protocols.
### Dose Adjustments
* **Renal Impairment (CrCl ≥ 50 mL/min):** No dose adjustment needed.
* **Renal Impairment (CrCl 20-49 mL/min):** Administer usual dose every 8 hours.
* **Renal Impairment (CrCl < 20 mL/min):** Administer usual dose every 12 hours.
* **Hemodialysis:** Administer usual dose every 12 hours and give an additional 2.25 grams dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment recommended.
### Contraindications
* Known severe allergic reaction to piperacillin, tazobactam, other beta-lactam antibiotics, or beta-lactamase inhibitors.
### Adverse Effects
* Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia.
* **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizure (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes.
### 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:** Piperacillin may decrease INR. Closely monitor INR.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance. Monitor methotrexate levels.
### Monitoring
* Renal function (BUN, creatinine)
* Liver function tests (AST, ALT)
* Complete blood count (CBC) with differential
* Electrolytes
* Signs and symptoms of infection resolution
* Signs and symptoms of adverse effects (e.g., rash, diarrhea)
### Clinical Pearls
* Reconstitute and dilute according to manufacturer instructions; infusion rate is crucial to prevent infusion reactions. Standard infusion time is 30 minutes. Extended infusion (4 hours) may be considered for patients with severe illness or specific pathogens, but this can alter the pharmacokinetic profile and requires careful consideration.
* The ratio of piperacillin to tazobactam is 8:1.
* Piperacillin/tazobactam has activity against *Pseudomonas aeruginosa*.
* Be aware of potential for cross-reactivity in patients with penicillin allergy, although the risk is generally lower with ureidopenicillins compared to older penicillins.
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*This information is intended for healthcare professionals and does not replace the need to consult the official prescribing information or a pharmacist for patient-specific guidance.*
