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# Piperacillin/Tazobactam (Zosyn)
## Overview
Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin, and tazobactam, 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
* Hospital-acquired pneumonia (including ventilator-associated pneumonia)
* Febrile neutropenia (often as empiric therapy)
## Adult Dosing
* **Standard Dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously.
* **High Dose (for severe infections or suspected resistant organisms):** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours intravenously. Some guidelines suggest 4.5 grams every 4 hours for very severe infections.
* **Duration:** Typically 7-10 days, depending on the infection, clinical response, and presence of surgical source control.
## Pediatric Dosing
Dosing is based on piperacillin component and typically calculated based on weight. Tazobactam dose is fixed relative to piperacillin.
* **3 months and older:**
* **General Infections:** 100 mg/kg piperacillin component every 8 hours. (e.g., 2.25g/0.28g per 25kg dose: 100mg/kg piperacillin * 25kg = 2500mg piperacillin / 1000 = 2.5g piperacillin; tazobactam is 1/8th of piperacillin dose).
* **Severe Infections (e.g., febrile neutropenia, HAP/VAP):** 100 mg/kg piperacillin component every 6 hours. Alternatively, 300 mg/kg/day divided every 6 or 8 hours.
* **Maximum Dose:** Generally capped at the adult dose of 4.5 grams per dose.
* **Renal Impairment:** Dosing adjustments are necessary (see below).
## Dose Adjustments
* **Renal Impairment (Adults):**
* CrCl > 40 mL/min: No adjustment needed.
* CrCl 20-40 mL/min: 2.25 grams every 6 hours.
* CrCl < 20 mL/min: 2.25 grams every 8 hours.
* **Hemodialysis:** 2.25 grams every 8 hours, plus an additional dose of 0.75 grams after each dialysis session.
* **Renal Impairment (Pediatrics):** Adjustments based on CrCl are also recommended. Consult specific pediatric guidelines or dosing calculators.
* **Hepatic Impairment:** No specific dosage adjustment is recommended, but caution is advised.
## Contraindications
* Known history of severe allergic reaction to penicillins, cephalosporins, or beta-lactamase inhibitors.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, hypokalemia.
* **Serious:** Clostridioides difficile-associated diarrhea (CDAD), hypersensitivity reactions (including anaphylaxis), seizure, interstitial nephritis, hemolytic anemia, hepatic dysfunction.
## Key Drug Interactions
* **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations.
* **Neuromuscular blocking agents:** May prolong neuromuscular blockade.
* **Warfarin:** Piperacillin may decrease the effect of warfarin; monitor INR closely.
* **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels.
## Monitoring
* **Renal function:** Especially in patients with pre-existing renal impairment or those receiving other nephrotoxic agents.
* **Electrolytes:** Particularly potassium, due to potential for hypokalemia.
* **Signs of hypersensitivity reactions:** Rash, itching, difficulty breathing.
* **Signs of C. difficile infection:** Diarrhea.
* **Therapeutic drug monitoring (TDM):** Not routinely recommended but may be considered in specific situations (e.g., critical illness, significant renal impairment).
## Clinical Pearls
* Piperacillin/tazobactam has a broad spectrum, but susceptibility testing is crucial, especially for gram-negative organisms like Pseudomonas aeruginosa.
* Can cause a non-allergic skin rash (maculopapular, pruritic) that is often dose-related and may be managed with antihistamines.
* Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated, but check manufacturer's specific instructions.
* The addition of tazobactam increases activity against many beta-lactamase producing organisms but does not extend coverage to all carbapenem-resistant Enterobacterales or extended-spectrum beta-lactamase (ESBL) producing organisms without specific susceptibility data.
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***Disclaimer:** This information is intended for healthcare professionals. Always consult the official prescribing information and relevant institutional protocols for complete and up-to-date guidance. Dosing may vary based on clinical context and patient-specific factors.
