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# Piperacillin/Tazobactam (Zosyn) ## Overview Piperacillin/tazobactam is a combination antibiotic consisting of piperacillin, a penicillin-class antibiotic, and tazobactam, a beta-lactamase inhibitor. It has a broad spectrum of 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 * Hospital-acquired pneumonia (including ventilator-associated pneumonia) * Empirical treatment of febrile neutropenia ## Adult Dosing * **Complicated Intra-abdominal Infections, Complicated Skin and Skin-Structure Infections, Community-Acquired Pneumonia, Hospital-Acquired Pneumonia:** * 3.375 grams every 6 hours or 4.5 grams every 8 hours intravenously. * Dosing duration typically 7 to 14 days depending on the indication and severity. * **Empirical Treatment of Febrile Neutropenia:** * 4.5 grams every 6 hours intravenously. * Duration depends on resolution of neutropenia and fever. * **Maximum Dose:** Not explicitly defined, but doses exceeding 4.5 grams every 6 hours are generally not recommended. ## Pediatric Dosing Dosing is based on piperacillin component: * **3 months and older:** * **Complicated Intra-abdominal Infections, Complicated Skin and Skin-Structure Infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered every 8 hours. * **Hospital-Acquired Pneumonia:** 75 mg piperacillin/9.375 mg tazobactam per kg per dose administered every 6 hours. * **Febrile Neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose administered every 6 hours. * **Maximum Pediatric Dose:** Maximum dose of 4.5 grams per dose. * **Note:** Due to the risk of kernicterus, avoid in neonates and infants <3 months. Dosing can be highly individualized and may require consultation with a pediatric infectious disease specialist or pharmacist. ## Dose Adjustments * **Renal Impairment:** * CrCl > 40 mL/min: No adjustment needed. * CrCl 20-40 mL/min: 2.25 grams every 6 hours or 3.375 grams every 8 hours. * CrCl < 20 mL/min: 2.25 grams every 8 hours or 3.375 grams every 12 hours. * For pediatric patients, adjust based on piperacillin component. * **Hepatic Impairment:** No specific dose adjustment recommended, but caution is advised. ## Contraindications * Known hypersensitivity to piperacillin, tazobactam, any other piperacillin/tazobactam component, or penicillins. * History of immediate or severe allergic reaction to beta-lactam antibiotics. ## Adverse Effects Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, constipation, abdominal pain. Serious: *Clostridioides difficile*-associated diarrhea, anaphylaxis, hypersensitivity reactions, seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic effects (e.g., neutropenia, thrombocytopenia), liver enzyme elevations. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations. * **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the effect of vecuronium. * **Warfarin:** Piperacillin may decrease the effect of warfarin; monitor INR closely. * **Methotrexate:** Piperacillin may decrease methotrexate clearance; monitor methotrexate levels. ## Monitoring * Renal function (baseline and periodically during therapy, especially in patients with pre-existing renal impairment). * Liver function tests (baseline and periodically). * Complete blood count (periodic monitoring for hematologic changes). * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of *C. difficile* infection. * Electrolytes, especially if patient is receiving concurrent diuretic therapy. ## Clinical Pearls * Dosing is often guided by local antibiograms and specific institutional protocols, particularly for indications like febrile neutropenia and healthcare-associated infections. * Piperacillin/tazobactam is often a preferred agent for empiric treatment of serious infections with suspected Gram-negative and anaerobic involvement. * Reconstituted solution should be used within 24 hours when refrigerated or within 12 hours at room temperature. * Monitor for signs of C. difficile-associated diarrhea. *** *Please verify current prescribing information and institutional guidelines before use.*