Tazobactum%2525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520piperacillin

# Piperacillin-Tazobactam ## Overview Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillin antibiotic, and tazobactam, a beta-lactamase inhibitor. Tazobactam protects piperacillin from degradation by beta-lactamase enzymes produced by many bacteria, thereby extending its spectrum of activity against beta-lactamase producing organisms. ## Primary Indications * Complicated intra-abdominal infections (cIAI) * Community-acquired pneumonia (CAP) * Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP) * Complicated skin and skin structure infections (cSSSI) * Febrile neutropenia (empiric treatment) * Complicated urinary tract infections (cUTI), including pyelonephritis ## Adult Dosing Standard dosing is **3.375 grams** (3g piperacillin/0.375g tazobactam) or **4.5 grams** (4g piperacillin/0.5g tazobactam) intravenously every **6 hours**. Infusion is typically over 30 minutes. Higher doses and more frequent administration may be used for severe infections or for specific pathogens based on susceptibility. For severe infections, **4.5 grams IV every 6 hours** is common. Maximum daily dose typically does not exceed **18 grams**. ## Pediatric Dosing Dosing varies by indication and patient weight. * **cIAI, cSSSI, CAP, HAP/VAP:** Recommended doses range from **80 mg/kg to 100 mg/kg of piperacillin component** every **6 to 8 hours**. Total daily dose of piperacillin should not exceed 18 grams. * **Febrile Neutropenia:** **100 mg/kg of piperacillin component** every **6 hours**. * **Neonates and Infants < 2 months:** Dosing is less established and requires careful consideration of weight and maturity. Consult specific guidelines. ## Dose Adjustments * **Renal Impairment:** Dose reduction and/or increased dosing interval is necessary for creatinine clearance (CrCl) < 40 mL/min. * CrCl 20-40 mL/min: **2.25g or 3.375g IV every 8 hours**. * CrCl < 20 mL/min: **2.25g IV every 8 hours**. * Hemodialysis: Administer dose after dialysis and increase frequency to every 8 hours. ## Contraindications * Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors. * History of cholestatic jaundice or hepatic dysfunction associated with piperacillin-tazobactam use. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia, constipation, elevated liver enzymes. * **Serious:** *Clostridioides difficile*-associated diarrhea (CDAD), hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis), seizures (especially with high doses or renal impairment), hematologic effects (neutropenia, thrombocytopenia, eosinophilia), hepatic dysfunction. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin serum concentrations. * **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** May decrease the efficacy of warfarin, leading to an increased INR. Close monitoring of INR is recommended. * **Methotrexate:** Piperacillin may decrease methotrexate clearance, requiring increased monitoring of methotrexate levels. ## Monitoring * **Renal function:** Monitor serum creatinine and adjust dosing as needed. * **Liver function:** Monitor liver enzymes (AST, ALT) periodically, especially in patients with pre-existing hepatic impairment. * **Hematologic parameters:** Monitor complete blood count (CBC) with differential and platelets, particularly with prolonged therapy. * **Signs of *C. difficile* infection:** Monitor for diarrhea. * **Clinical signs of infection:** Monitor for improvement in signs and symptoms of infection. ## Clinical Pearls * Piperacillin-tazobactam is a potent broad-spectrum agent. Use should be guided by culture and susceptibility data when available. * The extended infusion (e.g., over 4 hours) may improve efficacy for certain pathogens (e.g., *Pseudomonas aeruginosa*) and may be beneficial in critically ill patients. Confirm local protocols for extended infusions. * Ensure adequate hydration in patients receiving IV beta-lactams to minimize risk of neurotoxicity. * Discontinue if hypersensitivity reaction or significant *C. difficile*-associated diarrhea occurs. *** *Please verify current prescribing information and consult institutional protocols for the most up-to-date and specific guidance.*