Piperacillin%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520tazobactam%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252528zosyn%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252529

# Piperacillin-Tazobactam (Zosyn) ## Overview Piperacillin-tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. ## Primary Indications Treatment of moderate to severe infections caused by susceptible bacteria, including *Pseudomonas aeruginosa*, *Enterococcus faecalis*, *Staphylococcus aureus* (methicillin-susceptible strains), *Escherichia coli*, *Klebsiella pneumoniae*, *Proteus mirabilis*, *Bacteroides fragilis*, and other gram-positive, gram-negative, and anaerobic organisms. Common indications include pneumonia, intra-abdominal infections, skin and skin-structure infections, and febrile neutropenia. ## Adult Dosing * **Complicated Intra-abdominal Infections:** 3.375 grams IV every 6 hours. Duration is typically 4 to 7 days. * **Nosocomial Pneumonia:** 3.375 grams IV every 4 hours or 4.5 grams IV every 6 hours. Consider higher doses for severe infections or *Pseudomonas* infections. Duration is typically 7 days. * **Febrile Neutropenia:** 4.5 grams IV every 6 hours. Duration is typically 7 days or until resolution of neutropenia and fever. * **Uncomplicated Skin and Skin Structure Infections:** 3.375 grams IV every 6 hours. Duration is typically 7 days. Maximum daily dose is generally 18 grams (4.5 grams every 4 hours). ## Pediatric Dosing Dosing varies significantly by indication and age. Consult specific guidelines or institutional protocols. A general range for children aged 3 months and older is: * **3.0 grams/kg/day** of piperacillin activity divided into **4 doses** (e.g., 75 mg/kg/dose of piperacillin component, 9.375 mg/kg/dose of tazobactam component for a 4.5 g/0.5625 g formulation). * Doses should not exceed the maximum adult dose of 4.5 grams per dose. * For serious *Pseudomonas aeruginosa* infections, doses up to 5.0 grams of piperacillin activity per dose (or 12 grams/day of piperacillin activity) have been used in children > 6 months with cystic fibrosis. ## Dose Adjustments * **Renal Impairment:** Adjust dose and/or frequency based on creatinine clearance (CrCl). * CrCl 20-40 mL/min: Administer usual dose every 8 hours. * CrCl < 20 mL/min: Administer usual dose every 12 hours. * For doses of 4.5 grams every 4 hours, the dose should be reduced to 2.25 grams every 4 hours for CrCl 20-40 mL/min and 2.25 grams every 6-8 hours for CrCl < 20 mL/min. ## Contraindications Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation. ## Adverse Effects Common: Diarrhea, nausea, vomiting, rash, headache, insomnia, fever, elevated liver enzymes, injection site reactions. Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (rare, particularly with high doses or renal impairment), interstitial nephritis, hematologic abnormalities. ## Key Drug Interactions * **Probenecid:** May increase and prolong serum concentrations of piperacillin. * **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the action of neuromuscular blocking agents. * **Warfarin:** Piperacillin-tazobactam may reduce the efficacy of warfarin. Monitor INR closely. * **Methotrexate:** Piperacillin may decrease methotrexate levels. Monitor methotrexate levels. ## Monitoring * Renal function (especially with dose adjustments). * Liver function tests. * Complete blood count. * Signs and symptoms of infection. * Signs of hypersensitivity reactions. * For patients on warfarin, monitor INR. ## Clinical Pearls * Piperacillin-tazobactam has broad-spectrum activity, including against *Pseudomonas aeruginosa*. * The tazobactam component inhibits beta-lactamases, extending the spectrum of piperacillin. * Dosing frequency in adults with normal renal function is typically every 4 or 6 hours. * Reconstituted solutions are stable for 24 hours at room temperature or 48 hours if refrigerated. * Infuse over at least 30 minutes to minimize infusion reactions. *Always verify current prescribing information and institutional protocols before administering any medication.*