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# Piperacillin/Tazobactam ## Overview Piperacillin/tazobactam is an extended-spectrum penicillin combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria, including some strains resistant to other penicillins. ## Primary Indications * Complicated intra-abdominal infections * Complicated skin and skin structure infections * Community-acquired pneumonia * Hospital-acquired pneumonia (including ventilator-associated pneumonia) * Febrile neutropenia (empiric treatment) ## Adult Dosing * **Standard Dosing:** 3.375 grams (3g piperacillin/0.375g tazobactam) or 4.5 grams (4g piperacillin/0.5g tazobactam) intravenously every 6 or 8 hours. * **Severe Infections/Hospital-Acquired Pneumonia:** Doses up to 4.5 grams IV every 6 hours are common. * **Continuous Infusion:** Doses of 4.5 grams IV every 8 hours as a continuous infusion are also used, particularly for severe infections and in critical illness. This allows for higher drug exposure. ## Pediatric Dosing * **Patients 0 to < 1 year:** Dosing is based on piperacillin component: 75 to 100 mg/kg/dose IV every 6 to 8 hours. The maximum dose should not exceed the adult dose. Consider renal function. * **Patients 1 to < 12 years:** Dosing is based on piperacillin component: 50 to 75 mg/kg/dose IV every 6 to 8 hours. For severe infections, 100 mg/kg/dose IV every 8 hours may be used. The maximum dose should not exceed 4 grams of piperacillin per dose. * **Patients ≥ 12 years:** Dosing is the same as adult dosing. Dosing in neonates (<1 month) is complex and should be guided by specific institutional protocols or expert consultation due to immature renal and hepatic function. ## Dose Adjustments * **Renal Impairment:** * CrCl ≥ 40 mL/min: No adjustment needed. * CrCl 20-39 mL/min: Administer usual dose every 8 hours. * CrCl < 20 mL/min: Administer usual dose every 12 hours. * For continuous infusion, maintain infusion rate but consider increasing the dose proportionally to renal function. * **Hepatic Impairment:** No dose adjustment is typically required. * **Hemodialysis:** Administer usual dose every 12 hours and supplement with an additional 2.25g dose after each dialysis session. ## Contraindications * Known serious hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors. ## Adverse Effects * **Common:** Diarrhea, rash, nausea, vomiting, headache, insomnia, pruritus, urticaria. * **Serious:** Hypersensitivity reactions (including anaphylaxis), *Clostridioides difficile*-associated diarrhea, seizures (rare, particularly with high doses or renal impairment), neutropenia, thrombocytopenia, elevated liver enzymes, interstitial nephritis. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin/tazobactam serum concentrations. * **Neuromuscular Blocking Agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** May decrease the effect of warfarin, leading to increased INR. Monitor INR closely. * **Methotrexate:** May decrease methotrexate clearance. Monitor methotrexate levels. ## Monitoring * Signs and symptoms of infection. * Renal and hepatic function. * Electrolytes. * Complete blood count (CBC), especially in prolonged therapy or high doses, to monitor for neutropenia or thrombocytopenia. * Signs of hypersensitivity reactions. * INR if the patient is on warfarin. ## Clinical Pearls * Piperacillin/tazobactam has broad-spectrum activity, including *Pseudomonas aeruginosa*. * For empiric treatment of febrile neutropenia, it is often used in combination with an aminoglycoside or fluoroquinolone, depending on local resistance patterns and patient factors. * The beta-lactamase inhibitor tazobactam extends the spectrum of piperacillin to include many beta-lactamase-producing organisms. * Ensure adequate hydration and monitor for signs of dehydration, especially in pediatric patients and the elderly. * Reconstituted solutions are typically stable for 24 hours at room temperature or 48 hours refrigerated. Check manufacturer specific information. *** *This information is intended for healthcare professionals. Always consult the most current prescribing information and institutional guidelines before administering any medication. Dosing recommendations can vary based on patient-specific factors, clinical indication, and local protocols.*