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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 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
* Nosocomial pneumonia
* Febrile neutropenia (empiric treatment)
### Adult Dosing
The standard adult dose is 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 6 hours IV.
Higher doses of 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) every 6 hours IV may be used for more severe infections or those caused by less susceptible organisms.
For febrile neutropenia, 4.5 grams every 6 hours IV is often recommended.
Dosing frequency may be extended to every 8 hours for patients with severe renal impairment (CrCl < 20 mL/min). Continuous infusions are also an option, with total daily doses typically ranging from 12 grams to 18 grams of piperacillin.
### Pediatric Dosing
Dosing varies significantly by indication and weight. Local protocols should be consulted.
For children 0 to < 2 months: Dosing is highly individualized based on gestational age and weight; consult specific pediatric guidelines.
For children ≥ 2 months: Dosing is typically based on piperacillin component.
* Complicated intra-abdominal infections: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* Complicated skin and skin-structure infections: 75 mg piperacillin/9.375 mg tazobactam per kg per dose IV every 8 hours.
* Nosocomial pneumonia: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
* Febrile neutropenia: 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours.
Maximum dose generally not to exceed 4.5 grams per dose.
### Dose Adjustments
* **Renal Impairment:**
* CrCl 20-40 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) every 6 hours.
* CrCl < 20 mL/min: 2.25 grams (2g piperacillin/0.25g tazobactam) every 8 hours.
* For doses of 4.5 grams every 6 hours:
* CrCl 20-40 mL/min: 3.375 grams every 6 hours.
* CrCl < 20 mL/min: 2.25 grams every 6 hours.
* Patients on hemodialysis: 2.25 grams every 8 hours plus an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific dose adjustment is usually required.
### Contraindications
* Known history of hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors.
### Adverse Effects
Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, constipation.
Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (e.g., neutropenia, thrombocytopenia).
### Key Drug Interactions
* **Probenecid:** May increase and prolong serum concentrations of piperacillin/tazobactam.
* **Neuromuscular blocking agents:** Penicillins may prolong the neuromuscular blockade.
* **Warfarin:** May decrease INR. Monitor INR closely.
* **Methotrexate:** Penicillins may decrease methotrexate clearance. Monitor methotrexate levels.
* **Live bacterial vaccines:** May decrease efficacy.
### Monitoring
* Signs and symptoms of infection.
* Renal function (BUN, creatinine).
* Electrolytes.
* Liver function tests.
* Complete blood count (CBC) with differential, especially during prolonged therapy.
* Signs of hypersensitivity reactions.
* Bowel function for *C. difficile*.
### Clinical Pearls
* The combination of piperacillin with tazobactam extends the spectrum of activity against beta-lactamase producing organisms.
* Ensure adequate hydration during administration.
* Rapid infusion can cause excitatory effects. Administer over at least 30 minutes (or 4 hours for continuous infusion).
* Do not administer the 3.375g or 4.5g reconstituted solution for injection to patients requiring a 2.25g dose.
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**Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional protocols before administering any medication.
