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# Piperacillin-Tazobactam (Zosyn) ## Overview Piperacillin-tazobactam is a combination antibiotic consisting of an extended-spectrum penicillin (piperacillin) and a beta-lactamase inhibitor (tazobactam). ## Primary Indications * Complicated intra-abdominal infections (cIAI) * Complicated skin and skin structure infections (cSSSI) * Community-acquired pneumonia (CAP) * Hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP) * Empirical treatment of febrile neutropenia ## Adult Dosing * **Standard dose:** 3.375 grams (3g piperacillin/0.375g tazobactam) every 6 hours intravenously (IV). * **Higher dose for severe infections or HAP/VAP:** 4.5 grams (4g piperacillin/0.5g tazobactam) every 6 or 8 hours IV. Some protocols may recommend continuous infusion for severe infections. * Maximum daily dose is generally 18 grams (16g piperacillin/2g tazobactam). ## Pediatric Dosing * **Patients 12 years and older:** Same as adult dosing. * **Patients < 12 years:** * **3.0 grams/kg/day of piperacillin component, divided every 6 hours (e.g., 0.75 grams/kg every 6 hours).** * **Maximum piperacillin dose:** 4 grams per dose. * **Maximum tazobactam dose:** 0.5 grams per dose. * Note: These doses are for the combined formulation and are often based on the piperacillin component. Specific mg/kg recommendations for the combined product (e.g., 100mg piperacillin/12.5mg tazobactam per kg) may be used. Always confirm specific formulation dosing. ## Dose Adjustments * **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. For the standard 6-hour interval, administer every 8 hours. For the 8-hour interval, administer every 12 hours. Dosing in severe renal impairment (CrCl < 10 mL/min) or during intermittent hemodialysis may require further adjustment and consultation with pharmacy/nephrology. * **Hepatic Impairment:** No dose adjustment is typically required. ## Contraindications * Known hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors. * History of immediate and severe allergic reaction (anaphylaxis) to piperacillin, tazobactam, or other beta-lactam antibiotics. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, pruritus, urticaria, elevated liver enzymes, headache, insomnia, fever. * **Serious:** * **Hypersensitivity Reactions:** Including anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis. * **Clostridioides difficile-associated diarrhea (CDAD).** * **Hematologic effects:** Neutropenia, thrombocytopenia, anemia, prolonged bleeding times. * **Neurologic effects:** Seizures (especially at high doses or with renal impairment). * **Electrolyte abnormalities:** Hypernatremia (due to sodium content in the formulation, especially with higher doses). * **Renal injury.** ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin-tazobactam serum concentrations. * **Neuromuscular blocking agents:** May prolong neuromuscular blockade. * **Warfarin:** May decrease warfarin effect; monitor INR closely. * **Live bacterial vaccines:** May decrease efficacy. * **Methotrexate:** May increase methotrexate levels; monitor methotrexate levels. ## Monitoring * Renal function (BUN, creatinine) * Liver function tests (AST, ALT) * Complete blood count (CBC) * Signs and symptoms of infection * Electrolytes (especially sodium) * Signs of hypersensitivity reactions or CDAD ## Clinical Pearls * The sodium content of piperacillin-tazobactam can be significant, particularly at higher doses. Consider in patients with fluid restrictions or those at risk for hypernatremia. * Bacteremia and sepsis require appropriate cultures to be drawn before initiating antibiotic therapy. * Dosage adjustment is crucial in patients with renal impairment. * Continuous infusion may be considered for severe infections to maintain higher drug concentrations and potentially reduce resistance development. Consult local protocols for continuous infusion dosing. * Piperacillin-tazobactam provides broad coverage, including against many Gram-positive, Gram-negative (including *Pseudomonas aeruginosa*), and anaerobic organisms. *** **Disclaimer:** This information is intended for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.