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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor.
### Primary Indications
* Complicated intra-abdominal infections
* Complicated skin and skin structure infections
* Community-acquired pneumonia
* Nosocomial pneumonia
* Empirical treatment of febrile neutropenia
### Adult Dosing
Standard dose: 3.375 grams (piperacillin 3g/tazobactam 0.375g) or 4.5 grams (piperacillin 4g/tazobactam 0.5g) intravenously every 6 to 8 hours.
Dosing frequency and duration depend on the indication and severity of infection.
For severe infections or those caused by less susceptible organisms, doses up to 4.5 grams every 4 hours may be used.
### Pediatric Dosing
Dosing in pediatric patients is based on piperacillin component:
* **2 months to 12 years:** 90-100 mg piperacillin/kg/dose intravenously every 8 hours.
* **Children weighing >50 kg:** Use adult doses.
* Dosing should not exceed the maximum adult dose of 4.5 grams per dose.
### Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) or 3.375 grams (piperacillin 3g/tazobactam 0.375g) every 8 hours.
* CrCl < 20 mL/min: 2.25 grams (piperacillin 2g/tazobactam 0.25g) every 8 hours.
* Consider intermittent hemodialysis: Administer dose after each dialysis session.
* **Hepatic Impairment:** No specific dosing adjustments are typically recommended, but monitor for efficacy and toxicity.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillin antibiotics, or cephalosporins.
* History of cholestatic jaundice or hepatic dysfunction associated with piperacillin/tazobactam.
### Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, elevated liver enzymes (AST, ALT), eosinophilia, leukopenia.
Serious: *Clostridioides difficile*-associated diarrhea, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, seizures (especially with high doses or renal impairment).
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of neuromuscular blocking agents.
* **Warfarin:** May decrease the effect of warfarin; monitor INR.
* **Methotrexate:** May decrease methotrexate levels; monitor methotrexate levels.
* **Aminoglycosides:** While often co-administered for synergistic effect, potential for antagonism exists; consider separate administration if possible.
### Monitoring
* Renal function (CrCl) for dose adjustments.
* Liver function tests (AST, ALT) periodically, especially with prolonged therapy.
* Complete blood count (CBC) for hematologic changes.
* Signs and symptoms of infection for efficacy.
* Signs and symptoms of hypersensitivity reactions.
* Monitor for *C. difficile*-associated diarrhea.
### Clinical Pearls
* Piperacillin/tazobactam has a broad spectrum of activity including many Gram-positive, Gram-negative, and anaerobic bacteria, but resistance can emerge.
* The beta-lactamase inhibitor tazobactam extends the spectrum of piperacillin against beta-lactamase producing organisms.
* Renal dose adjustments are critical.
* Be aware of potential for cross-reactivity in patients with penicillin allergy.
* Consider de-escalation of therapy once culture and sensitivity results are available.
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*This information is intended for healthcare professionals and should not be used as a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any treatment decisions.*
