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## Piperacillin-Tazobactam (Zosyn) ### Overview Piperacillin-tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It has broad-spectrum activity 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 * Nosocomial pneumonia * Febrile neutropenia (empiric treatment) ### Adult Dosing Common doses are 3.375 g (piperacillin 3 g / tazobactam 0.375 g) or 4.5 g (piperacillin 4 g / tazobactam 0.5 g) intravenously every 6 or 8 hours. The specific dose and frequency depend on the severity and type of infection. * **Complicated Intra-abdominal Infections:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours for 4-7 days. * **Complicated Skin and Skin Structure Infections:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours for 7-10 days. * **Community-Acquired Pneumonia:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours for 7 days. * **Nosocomial Pneumonia:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours. Higher doses (e.g., 4.5 g IV every 6 hours) may be considered for severe infections or documented *Pseudomonas aeruginosa* or other resistant organisms. * **Febrile Neutropenia:** Typically 4.5 g IV every 6 hours for 7 days or until neutropenia resolves and fever has been absent for 48 hours. **Maximum dose:** Generally not to exceed 4.5 g every 6 hours. ### Pediatric Dosing Dosing in pediatric patients is typically based on the piperacillin component. * **Patients 0 to < 6 months:** Dosing varies significantly based on gestational age and weight. Consult specific pediatric guidelines or formulary. A common regimen is 75 mg/kg/dose (piperacillin component) every 8-12 hours. * **Patients ≥ 6 months:** * **Complicated intra-abdominal infections:** 90-100 mg/kg/dose (piperacillin component) every 6 hours. Maximum 4.5 g/dose. * **Complicated skin and skin structure infections:** 90-100 mg/kg/dose (piperacillin component) every 6 hours. Maximum 4.5 g/dose. * **Febrile neutropenia:** 100 mg/kg/dose (piperacillin component) every 6 hours. Maximum 4.5 g/dose. * **Congenital cystic lung disease:** 100 mg/kg/dose (piperacillin component) every 6 hours. Maximum 4.5 g/dose. Total daily dose should not exceed 16 g of piperacillin. ### Dose Adjustments * **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For standard dosing intervals of 6 or 8 hours, administer every 8 or 12 hours, respectively. For 4.5 g every 6 hours, administer 2.25 g every 6 hours. Further adjustments may be needed based on CrCl < 10 mL/min and/or dialysis status. * **Hepatic Impairment:** No dose adjustment recommended. ### Contraindications * Known hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or cephalosporins. ### Adverse Effects Common: Diarrhea, rash, nausea, vomiting, headache, insomnia, fever, eosinophilia, elevated liver enzymes. Serious: *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), neutropenia, thrombocytopenia. ### Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations. * **Aminoglycosides:** May have additive or synergistic activity but also potential for antagonism. Concurrent use should be based on susceptibility data and clinical context. In vitro, piperacillin can inactivate aminoglycosides in the IV bag, therefore separate administration. * **Warfarin:** May decrease INR. Monitor INR closely. * **Neuromuscular Blocking Agents:** Penicillins can potentiate neuromuscular blockade. ### Monitoring * Renal function (especially with co-administered nephrotoxic agents). * Liver function tests. * Hematologic parameters (complete blood count). * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of *Clostridioides difficile* infection. ### Clinical Pearls * Administer by slow intravenous infusion over 30 minutes. * Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated. * Consider the spectrum of activity and local resistance patterns when choosing empiric therapy. * High doses and prolonged durations of therapy increase the risk of adverse effects, including *C. difficile*-associated diarrhea and neuromuscular blockade. *** *Disclaimer: This information is intended for educational purposes and should not replace current prescribing information or professional medical advice. Always verify current dosing, indications, and safety information with the official drug product labeling and institutional protocols.*