Piperacillin%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520tazobactam%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252520%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252528zosyn%25252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252525252529

# Piperacillin/Tazobactam (Zosyn) ## Overview Piperacillin/tazobactam is an extended-spectrum penicillin antibiotic combined with a beta-lactamase inhibitor. It is active against many Gram-positive, Gram-negative, and anaerobic bacteria. ## Primary Indications * Complicated intra-abdominal infections * Complicated skin and skin structure infections * Community-acquired pneumonia * Hospital-acquired pneumonia (including ventilator-associated pneumonia) * Febrile neutropenia (in combination with an aminoglycoside) ## Adult Dosing * **Complicated Intra-abdominal Infections, Complicated Skin and Skin Structure Infections, Community-Acquired Pneumonia, Hospital-Acquired Pneumonia:** * **3.375 grams every 6 hours** or **4.5 grams every 6 or 8 hours** IV. * Dosing frequency depends on the severity of infection and institutional guidelines. * Maximum daily dose typically not to exceed 18 grams. * **Febrile Neutropenia:** * **4.5 grams every 6 hours** IV. Dosing duration is typically 7-14 days, depending on the infection and clinical response. ## Pediatric Dosing * **Patients 3 months and older:** Dosing is based on piperacillin component. * **Complicated Intra-abdominal Infections:** 80-100 mg piperacillin/10 mg tazobactam per kg per dose IV every 6 hours. * **Hospital-Acquired Pneumonia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours. * **Febrile Neutropenia:** 100 mg piperacillin/12.5 mg tazobactam per kg per dose IV every 8 hours. * Maximum pediatric doses should not exceed adult doses. Weight-based dosing may be adjusted based on severity and susceptibility of the pathogen. ## Dose Adjustments * **Renal Impairment (CrCl < 40 mL/min):** * **CrCl 20-40 mL/min:** 2.25 grams every 6 hours or 3.375 grams every 8 hours. * **CrCl < 20 mL/min:** 2.25 grams every 8 hours or 3.375 grams every 12 hours. * Dosing should be adjusted for CrCl < 40 mL/min. If a patient is on continuous renal replacement therapy (CRRT), dosing varies and consultation with pharmacy is recommended. * **Hepatic Impairment:** No dose adjustment is typically required, but caution is advised. ## Contraindications * Hypersensitivity to piperacillin, tazobactam, other penicillins, or beta-lactamase inhibitors. * History of a severe allergic reaction (e.g., anaphylaxis) to a beta-lactam antibiotic. ## Adverse Effects * **Common:** Diarrhea, nausea, vomiting, rash, pruritus, headache, insomnia, fever, eosinophilia, elevated liver enzymes (AST, ALT). * **Serious:** Clostridioides difficile-associated diarrhea, hypersensitivity reactions (including anaphylaxis), seizures (especially with high doses or renal impairment), interstitial nephritis, hematologic changes (neutropenia, thrombocytopenia, leukopenia, prolonged bleeding time). ## Key Drug Interactions * **Aminoglycosides:** May have synergistic or additive activity, but potential for antagonism if mixed in the same IV line. Monitor for efficacy and toxicity. * **Probenecid:** May increase and prolong piperacillin/tazobactam plasma concentrations. * **Neuromuscular Blocking Agents:** Piperacillin may prolong the neuromuscular blockade. * **Warfarin:** May decrease the effect of warfarin; monitor INR closely. * **Live Vaccines:** Avoid concurrent administration. ## Monitoring * Renal function (serum creatinine, BUN). * Liver function tests (AST, ALT). * Complete blood count (CBC) with differential and platelets, especially with prolonged therapy. * Signs and symptoms of infection (fever, WBC count, culture results). * Signs and symptoms of hypersensitivity reactions. * Bowel function for C. difficile. ## Clinical Pearls * Piperacillin/tazobactam is a broad-spectrum agent frequently used for empiric therapy of serious infections, including those with potential for Gram-negative or anaerobic involvement. * Reconstitution and dilution are required prior to IV administration. Infusion should be over at least 30 minutes to minimize infusion-related reactions. * The beta-lactamase inhibitor tazobactam broadens the spectrum of piperacillin to include many beta-lactamase producing organisms. * Due to its broad spectrum, stewardship principles should be applied, and de-escalation to narrower-spectrum agents should be considered when pathogen susceptibility is known. * Use with caution in patients with known penicillin allergy. Skin testing may be considered in select patients. *** **Disclaimer:** This information is intended for healthcare professionals and does not replace professional judgment. Always consult the most current prescribing information and institutional guidelines before administering any medication.