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# Piperacillin/Tazobactam (Zosyn) ## Overview Piperacillin/tazobactam is a combination of an extended-spectrum penicillin antibiotic and a beta-lactamase inhibitor. ## Primary Indications * Complicated intra-abdominal infections * Complicated skin and skin structure infections * Community-acquired pneumonia * Hospital-acquired pneumonia (including ventilator-associated pneumonia) ## Adult Dosing * **Standard Dose:** 3.375 g (3 g piperacillin/0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin/0.5 g tazobactam) IV every 6 or 8 hours. * **Higher Doses:** May be used for severe infections, particularly those caused by less susceptible organisms or in critically ill patients. Dosing is often based on local antibiogram and institutional guidelines, but may reach 4.5 g every 4 hours in some protocols. ## Pediatric Dosing * **For patients ≥ 12 years of age:** Same as adult dosing. * **For patients < 12 years of age:** * **Intra-abdominal infections:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours. * **Other infections:** 80 mg piperacillin/10 mg tazobactam per kg per dose IV every 8 hours. * **Maximum dose:** Do not exceed the adult dose of 4.5 g per dose. * **Premature infants (< 29 weeks gestation):** Dosing may require specific adjustments; consult literature. ## Dose Adjustments * **Renal Impairment (CrCl < 20 mL/min):** Reduce frequency. * For 3.375 g every 6 hours regimen: Administer 2.25 g every 8 hours. * For 4.5 g every 8 hours regimen: Administer 3.375 g every 12 hours. * For 4.5 g every 6 hours regimen: Administer 3.375 g every 8 hours. * **Renal Impairment (CrCl 20-50 mL/min):** Reduce dose or frequency based on institutional guidelines; typically, an increase in interval to every 8 hours for standard dosing is considered. * **Hemodialysis:** Administer dose after dialysis and supplement with an additional dose every 12 hours. * **Hepatic Impairment:** No specific dose adjustment is recommended, but monitor closely. ## Contraindications * Known history of severe allergic reaction to piperacillin, other penicillin antibiotics, or beta-lactamase inhibitors. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, abdominal pain, leukopenia, eosinophilia. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hepatotoxicity, hematologic effects (neutropenia, thrombocytopenia). ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations. * **Vecuronium:** Piperacillin may prolong the neuromuscular blockade 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 (BUN, creatinine). * Liver function tests (AST, ALT). * Complete blood count (CBC) with differential, especially with prolonged therapy. * Electrolytes. * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of *C. difficile*-associated diarrhea. ## Clinical Pearls * Piperacillin/tazobactam is a broad-spectrum agent often reserved for moderate to severe infections or polymicrobial infections. * Reconstituted solutions are stable for 24 hours at room temperature or 48 hours refrigerated. Further dilution in IV fluid is required for infusion. * Infuse over at least 30 minutes to minimize infusion-related reactions. * Consider potential for cross-reactivity in patients with penicillin allergies, although rates are generally low for non-urticarial reactions. * Discontinue if hypersensitivity reaction occurs. *** *Disclaimer: This information is intended for educational purposes and does not substitute for professional medical advice. Always consult current prescribing information, institutional guidelines, and a qualified healthcare provider for specific patient care decisions.*