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## Piperacillin/Tazobactam (Zosyn)
### Overview
Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), 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 Dosing:** 3.375 g (3 g piperacillin/0.375 g tazobactam) or 4.5 g (4 g piperacillin/0.5 g tazobactam) every 6 or 8 hours.
* **Dosing Frequency:** Typically every 6 hours for severe infections or *Pseudomonas aeruginosa* coverage, and every 8 hours for less severe infections. Dosing frequency may be extended to every 8 hours for moderate infections.
* **Duration:** Varies based on infection type and severity, generally 4-14 days.
### Pediatric Dosing
* **Patients 0 to < 12 months:** Dosing is based on piperacillin weight and should follow institutional guidelines. Generally 80 mg piperacillin/10 mg tazobactam per kg per dose every 8 hours.
* **Patients 1 to < 12 years:** Dosing is based on piperacillin weight.
* **Standard Dosing:** 90-100 mg piperacillin/11.25-12.5 mg tazobactam per kg per dose every 6 or 8 hours.
* **Maximum Dose:** Not to exceed 4.5 g per dose.
* **Adolescents ≥ 12 years:** Use adult dosing.
* **Renal Impairment:** Dosing adjustments are required in pediatric patients with renal impairment.
### Dose Adjustments
* **Renal Impairment (CrCl > 40 mL/min):** No adjustment needed.
* **Renal Impairment (CrCl ≤ 40 mL/min):**
* **CrCl 20-40 mL/min:** Reduce dose frequency to every 8 hours (if previously every 6 hours) or every 12 hours (if previously every 8 hours).
* **CrCl < 20 mL/min:** Reduce dose frequency to every 12 hours.
* **Hemodialysis:** Administer dose every 8 hours and supplement with an additional dose after each dialysis session.
* **Hepatic Impairment:** No specific adjustment recommended.
### Contraindications
* Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation.
* History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic.
### Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, fever, rash.
* **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis.
### Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade.
* **Methotrexate:** May decrease methotrexate serum levels. Monitor methotrexate levels closely.
* **Warfarin:** May decrease the efficacy of warfarin. Monitor INR closely.
### Monitoring
* Renal function (especially in patients with pre-existing renal disease or receiving concurrent nephrotoxic agents).
* Liver function tests.
* Complete blood count (CBC) with differential and platelet count, particularly with prolonged therapy.
* Signs and symptoms of hypersensitivity reactions.
* Signs and symptoms of *C. difficile*-associated diarrhea.
### Clinical Pearls
* Administer intravenously over at least 30 minutes to reduce the risk of infusion-related reactions.
* The 3.375 g formulation contains 3 g piperacillin and 0.375 g tazobactam. The 4.5 g formulation contains 4 g piperacillin and 0.5 g tazobactam.
* Dosing for *Pseudomonas aeruginosa* or severe infections often favors the every 6-hour dosing interval, although every 8 hours may be appropriate based on clinical response and susceptibility.
* The choice of dosing interval (6 vs. 8 hours) and total daily dose should be guided by institutional protocols, local antibiogram data, and patient-specific factors.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the current prescribing information and institutional guidelines for complete details.*
