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# Piperacillin/Tazobactam ## Overview Piperacillin/tazobactam is a combination antibiotic consisting of a penicillin-class beta-lactam antibiotic (piperacillin) and a beta-lactamase inhibitor (tazobactam). It has a broad spectrum of activity against many Gram-positive, Gram-negative, and anaerobic bacteria. ## Primary Indications * Complicated intra-abdominal infections * Complicated skin and skin structure infections (including diabetic foot infections) * Community-acquired pneumonia * Hospital-acquired pneumonia (including ventilator-associated pneumonia) * Febrile neutropenia (empiric treatment) ## Adult Dosing * **Standard Dose:** 3.375 grams (piperacillin 3 grams / tazobactam 0.375 grams) intravenously every 6 hours. * **High Dose (for severe infections or infections due to less susceptible organisms):** 4.5 grams (piperacillin 4 grams / tazobactam 0.5 grams) intravenously every 6 or 8 hours. * **Maximum Daily Dose:** Typically 18 grams (piperacillin 16 grams / tazobactam 2 grams) per day, but may be higher in specific indications or under institutional guidelines. * **Duration:** Varies by indication and clinical response, typically 7-14 days. ## Pediatric Dosing * **Children < 12 years:** Dosing is weight-based. The specific ratio of piperacillin to tazobactam and the total daily dose will depend on the indication and institutional protocols. * **Complicated intra-abdominal infections:** 90-100 mg piperacillin/kg/day (as piperacillin component) divided into 3 or 4 doses. * **Febrile neutropenia:** 100 mg piperacillin/kg/dose (as piperacillin component) every 8 hours. * **Maximum pediatric dose:** Generally does not exceed the maximum adult dose. * **Children ≥ 12 years:** Dosing is the same as adults. ## Dose Adjustments * **Renal Impairment (CrCl < 20 mL/min):** Reduce dose frequency. * For 3.375 g every 6 hours, administer every 8 hours. * For 4.5 g every 6 hours, administer every 8 hours. * For 4.5 g every 8 hours, administer every 12 hours. * Consider a loading dose of 2.25 g followed by maintenance doses. * **Hemodialysis:** Administer dose after dialysis. An additional 0.75 g dose may be required after each dialysis session. * **Hepatic Impairment:** No dose adjustment is typically required. ## Contraindications * Hypersensitivity to piperacillin, tazobactam, other penicillinase-resistant penicillins, or any component of the formulation. * History of immediate or severe allergic reaction to penicillins, cephalosporins, or other beta-lactam antibiotics. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia. * **Serious:** *Clostridioides difficile*-associated diarrhea, hypersensitivity reactions (anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic changes (neutropenia, thrombocytopenia, eosinophilia), liver enzyme elevations. ## Key Drug Interactions * **Probenecid:** May increase and prolong piperacillin serum concentrations. * **Neuromuscular blocking agents (e.g., vecuronium):** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** Piperacillin may decrease the effect of warfarin, leading to an increased INR. Monitor INR closely. * **Methotrexate:** Piperacillin 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) if prolonged therapy is expected. * Liver function tests (LFTs) if prolonged therapy is expected. * INR if co-administered with warfarin. ## Clinical Pearls * Piperacillin/tazobactam is often a drug of choice for empirical treatment of serious infections, especially when Gram-negative and anaerobic coverage is needed. * Reconstituted solutions should be used promptly. * Rapid infusion can cause local irritation and phlebitis; administer over at least 30 minutes. * Doses and frequencies can vary significantly based on institutional protocols and specific patient factors. *** *Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and institutional guidelines before administering any medication.*