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# Piperacillin-Tazobactam ## Overview Piperacillin-tazobactam is a combination antibiotic consisting of piperacillin, a broad-spectrum penicillinase-susceptible penicillin, and tazobactam, a beta-lactamase inhibitor. ## Primary Indications * Complicated and uncomplicated intra-abdominal infections * Complicated and uncomplicated skin and skin structure infections * Community-acquired pneumonia * Nosocomial pneumonia * Bacterial meningitis (including certain Gram-negative pathogens) * Febrile neutropenia ## Adult Dosing * **Complicated Intra-abdominal Infections, Nosocomial Pneumonia, Moderate to Severe Community-Acquired Pneumonia, Febrile Neutropenia:** Typically 3.375 g IV every 6 hours or 4.5 g IV every 8 hours. * **Severe or Life-Threatening Infections:** Doses may be increased up to 4.5 g IV every 4 hours. * **Duration:** Varies based on indication, severity, and pathogen (e.g., 7 days for complicated intra-abdominal infections, 7-10 days for community-acquired pneumonia, 24 hours after resolution of fever and neutropenia for febrile neutropenia). ## Pediatric Dosing * **Patients 0 to 12 months:** Dosing is not well-established and is based on piperacillin component, typically 75-100 mg piperacillin/kg/day divided into 3-4 doses IV. Tazobactam dose is 3.75 mg/kg/day. * **Patients 1 to 12 years:** * **Complicated Intra-abdominal Infections:** 100 mg piperacillin/kg/day, not to exceed 3.375 g per dose, administered IV every 6 hours. Tazobactam dose is 12.5 mg/kg/day. * **Nosocomial Pneumonia:** 100 mg piperacillin/kg/day, not to exceed 4.5 g per dose, administered IV every 6 hours. Tazobactam dose is 12.5 mg/kg/day. * **Pediatric patients weighing >50 kg:** Dosing for adults should be used. ## Dose Adjustments * **Renal Impairment:** * CrCl 20-40 mL/min: Reduce dose by 25% (e.g., 3.375 g q8h, 4.5 g q12h). * CrCl <20 mL/min: Reduce dose by 50% (e.g., 2.25 g q6h, 3.375 g q12h). * Hemodialysis: Give usual dose every 8 hours, with an additional 0.75 g dose after each hemodialysis session. * **Hepatic Impairment:** No specific dose adjustment, but monitor closely. ## Contraindications * Hypersensitivity to piperacillin, tazobactam, or other beta-lactam antibiotics. * History of immediate or severe allergic reaction to penicillin or cephalosporins. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, headache, insomnia. * **Serious:** Hypersensitivity reactions (including anaphylaxis), C. difficile-associated diarrhea, seizures (especially with high doses or renal impairment), hematologic effects (neutropenia, thrombocytopenia, eosinophilia). ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin-tazobactam serum levels. * **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** May decrease warfarin effect; monitor INR closely. * **Methotrexate:** May decrease methotrexate clearance; monitor methotrexate levels. ## Monitoring * Renal function (CrCl) for dose adjustments. * Signs and symptoms of hypersensitivity reactions. * Signs and symptoms of C. difficile-associated diarrhea. * Complete blood count (CBC) with differential, especially with prolonged therapy. * Liver function tests (LFTs). * INR if patient is on warfarin. ## Clinical Pearls * The 3.375 g formulation contains 3 g piperacillin and 0.375 g tazobactam. The 4.5 g formulation contains 4 g piperacillin and 0.5 g tazobactam. * Reconstituted solutions should be used within specified timeframes at room temperature or refrigerated to maintain potency. * Administer IV infusion over at least 30 minutes. Rapid infusion can cause injection site reactions. * Consider local resistance patterns when selecting empiric therapy. * Dosing in critically ill patients or those with altered pharmacokinetics may require individualized adjustments. --- *This information is intended for healthcare professionals and does not substitute for comprehensive prescribing information. Always verify the most current prescribing information with official drug labels or reliable drug databases.*