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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active 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)
* Aspiration pneumonia
## Adult Dosing
* **Standard Dose:** 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) intravenously every 6 hours.
* **Higher Dose (for severe infections or suspected resistant organisms):** 4.5 grams (4 grams piperacillin/0.5 grams tazobactam) intravenously every 6 or 8 hours.
* **Duration:** Typically 7-14 days, depending on infection severity and clinical response.
## Pediatric Dosing
Dosing is based on piperacillin component and gestational age/postnatal age:
* **Patients > 12 weeks gestational age:** 90-100 mg piperacillin/11.25-12.5 mg tazobactam per kg per dose intravenously every 8 hours.
* **Patients ≤ 12 weeks gestational age:** 60-75 mg piperacillin/7.5-9.375 mg tazobactam per kg per dose intravenously every 8 or 12 hours, depending on post-natal age.
* **Maximum dose per dose:** Generally not to exceed 4.5 grams of piperacillin/0.5 grams of tazobactam.
* **Maximum dose per day:** Generally not to exceed 18 grams of piperacillin/2.25 grams of tazobactam.
* *Note: Pediatric dosing can be complex and may depend on specific indications and local protocols.*
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: Reduce dose frequency to every 8 hours.
* CrCl < 20 mL/min: Reduce dose frequency to every 12 hours.
* For higher doses (e.g., 4.5g Q6H), dose adjustment to every 8H or 12H may be necessary based on CrCl.
* **Hepatic Impairment:** No specific dose adjustment recommended, but caution advised.
## Contraindications
* Known hypersensitivity to piperacillin, tazobactam, other penicillins, or cephalosporins.
* History of immediate or severe allergic reaction to beta-lactam antibiotics.
## Adverse Effects
* **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, pruritus, fever, eosinophilia.
* **Serious:**
* **Hypersensitivity Reactions:** Anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
* **Clostridioides difficile-associated diarrhea (CDAD).**
* **Hematologic effects:** Neutropenia, thrombocytopenia, prolonged bleeding time.
* **Hepatic effects:** Elevated liver enzymes, cholestatic hepatitis.
* **Renal effects:** Interstitial nephritis, acute kidney injury.
* **Neurologic effects:** Seizures (more common with high doses or renal impairment).
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents (e.g., vecuronium):** May prolong neuromuscular blockade.
* **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely.
* **Methotrexate:** May decrease methotrexate clearance and increase its toxicity.
## Monitoring
* **Renal function:** Baseline and periodically, especially in patients with known renal impairment or those receiving nephrotoxic agents.
* **Liver function tests:** Baseline and periodically.
* **Complete blood count:** Monitor for hematologic changes.
* **Electrolytes:** Especially with prolonged therapy or in patients with renal impairment.
* **Signs and symptoms of hypersensitivity reactions and CDAD.**
## Clinical Pearls
* Piperacillin/tazobactam is a broad-spectrum agent often reserved for more serious or hospital-acquired infections due to its spectrum and potential for resistance development.
* Reconstituted solution must be administered within 24 hours when stored at room temperature or within 48 hours when refrigerated.
* When administered via IV infusion, the recommended dilution is typically 50-100 mL of compatible diluent over 30 minutes. Rapid infusion may increase the risk of seizures.
* The beta-lactamase inhibitor tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing organisms.
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*Disclaimer: This information is intended for healthcare professionals. Always consult the official prescribing information and relevant clinical guidelines before making treatment decisions. Dosing and recommendations may vary based on patient-specific factors and institutional protocols.*
